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sified as an IHDI grade III hip, whereas the left hip was classified as grade II. (D) Final case example of an AP pelvic radiograph of an infant with bilateral DDH. Both hips were classified as IHDI grade IV. Note that all hips in the case examples could be classified, although the ossific nucleus was variably present. Interobserver Reliability We noted a “high to very high” level of agreement between all observers when classifying the severity of DDH with the IHDI classification system, with an ICC of 0.90 [95% confidence interval (CI), 0.83- 0.95] for the right hip and an ICC of 0.95 (95% CI, 0.91-0.98) for the left hip. Using the Tönnis classification method, there was a “moderate to high” level of agreement between all observers with an ICC of 0.63 (95% CI, 0.46-0.80) for the right hip and an ICC of 0.63 (95%CI, 0.43-0.78) for the left hip. For the IHDI method, there were no significant differences between the ICCs of the 6 consultant pediatric orthopedic surgeons (0.90 and 0.95) for the right and left hips, respectively, and the 2 trainees (0.95 and 0.98) for the right and left hips respectively.

Using the Tönnis classification method, there was a “moderate to high” level of agreement between all observers with an ICC of 0.63 (95% CI, 0.46-0.80) for the right hip and an ICC of 0.63 (95%CI, 0.43-0.78) for the left hip. For the IHDI method, there were no significant differences between the ICCs of the 6 consultant pediatric orthopedic surgeons (0.90 and 0.95) for the right and left hips, respectively, and the 2 trainees (0.95 and 0.98) for the right and left hips respectively. DISCUSSION Although ultrasound is typically used for infants under the age of 6 months (who typically have unossified epiphyses), frontal plane pelvis radiographs are still frequently used across the world to diagnose and/or monitor DDH in older infants and children. Common practice divides severity into (1) dysplasia, (2) subluxation, and (3) dislocation. However, this practice does not allow accurate assessment of intermediate degrees of hip displacement. Although various radiographic parameters have been described to evaluate treatment results or quantify the deformity in acetabular and proximal femoral development, few classification systems exist to evaluate the severity of DDH on plain radiographs.

low accurate assessment of intermediate degrees of hip displacement. Although various radiographic parameters have been described to evaluate treatment results or quantify the deformity in acetabular and proximal femoral development, few classification systems exist to evaluate the severity of DDH on plain radiographs. We are aware of 3 published radiographic methods for evaluation of DDH severity at time of diagnosis. One is the method of Yamamuro and Chene10 that measures the distance from the center of the metaphysis to the H-line and the distance between the center of the metaphysis and the medial wall of the acetabulum (Fig. 5). Although this measurement has been proven reliable, it is a continuous variable that has not been divided into categories for comparative purposes. FIGURE 5 Yamamuro measurement method. Y indicates Y-line; A, Yamamuro-A; B, Yamamuro-B; H, Hilgenreiner-H; D, Hilgenreiner-D; h/b and c/b ratio, Smith’s ratio for superior and lateral displacement. Reproduced with permission from Boniforti et al.14

Radial proximal metaepiphyseal fractures are uncommon and account for 5% to 10% of all elbow fractures in skeletally immature patients.1–6 The frequency of associated lesions is quite variable, 15% to 60% in reported series.2–5,7–9 The treatment of radial neck fractures in children varies according to the fracture’s displacement, angulation, and skeletal maturity. Most fractures are nondisplaced or minimally displaced and can be treated with closed reduction and casting with a good outcome.10,11 There is a general agreement that displaced radial neck fractures with >30-degree angulation should be surgically treated.9,11–13 Treatment options include percutaneous pin reduction,8,14,15 elastic stable intramedullary nailing,5,15–18 and open reduction with or without internal fixation.3,9,17,19 Open reduction is a method of treatment often used in comminuted fractures or in fractures with a completely displaced head anteriorly or posteriorly on the radial metaphysis and when closed reduction has failed. Reports in the literature note higher rates of complications after open compared with closed reduction.17,19–21 Most authors agree that worse results may follow open treatment but it is the more severe fractures that warrant a more aggressive approach. Whether poor results are a consequence of treatment or the magnitude of the bony and soft tissue injury is not clear. In series reported in the literature, when the head of the radius remains displaced >30% and angulated >45 degrees after attempts of closed or percutaneous reduction, an open reduction is indicated.2,5,19,20

Most authors agree that worse results may follow open treatment but it is the more severe fractures that warrant a more aggressive approach. Whether poor results are a consequence of treatment or the magnitude of the bony and soft tissue injury is not clear. In series reported in the literature, when the head of the radius remains displaced >30% and angulated >45 degrees after attempts of closed or percutaneous reduction, an open reduction is indicated.2,5,19,20 The aim of the study is to analyze the outcomes of patients with a completely displaced and angulated (>60 degrees) fracture who underwent open reduction when closed reduction failed. Results were reviewed at a significant follow-up time and factors leading to poor results were identified METHODS All patients and their parents gave informed consent before being included in the study. This retrospective research was approved by our institutional ethics committee and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki as revised in 2000. Between 2000 and 2009, 195 patients with radial neck fractures were treated at our Division, a large, metropolitan, pediatric referral center. All patients had a review of their clinical charts and radiographs from initial injury to final follow-up.

METHODS All patients and their parents gave informed consent before being included in the study. This retrospective research was approved by our institutional ethics committee and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki as revised in 2000. Between 2000 and 2009, 195 patients with radial neck fractures were treated at our Division, a large, metropolitan, pediatric referral center. All patients had a review of their clinical charts and radiographs from initial injury to final follow-up. Inclusion criteria for the study were: (a) completely displaced and/or angulated radial neck fractures with or without associated injuries that could not be reduced by manipulation (with or without percutaneous K wires) under general anesthesia, and treated with open reduction; (b) patients with open growth plates of the elbow at the time of the injury; (c) minimum follow-up of 3 years. Exclusion criteria were: (a) open fracture; (b) lack of complete medical records or radiograph series (preoperative, postoperative, at 1 mo, at 6 mo, and at final follow-up). We used the O’Brien classification22 based on the angulation of the radial neck. Angulation was measured between the superior articular surface of the displaced radial head and the shaft of the radius. Displacement was also measured as the extent of lateral shift of the fragment by the distance from the center of the radial head to a line along the axis of the upper radius.

tion of the radial neck. Angulation was measured between the superior articular surface of the displaced radial head and the shaft of the radius. Displacement was also measured as the extent of lateral shift of the fragment by the distance from the center of the radial head to a line along the axis of the upper radius. Treatment varied: 111 of the 195 patients with nondisplaced or minimally displaced fractures were managed with simple cast immobilization, 56 underwent a manipulative closed reduction, 36 with K wire guidance, and 20 without K wires under general anesthesia and then immobilization in a cast. Twenty-eight patients had fractures with complete displacement and radial neck angulation of >60 degrees that could not be reduced by manipulation (with or without percutaneous K wires) under general anesthesia and underwent an open reduction and formed the cohort for this study. At follow-up, the carrying angle in full elbow extension and the range of motion (ROM) of the elbow and forearm were measured bilaterally. We recorded clinical results as good, fair, or poor according to the range of movement (pronation, supination, flexion, extension) and the presence of pain as per the Steinberg and Rodriguez-Merchan classification.23 We also evaluated any change in the carrying angle and axial deformity. Flexion and extension of the elbow, pronation and supination of the forearm, and the valgus angle of the extended elbow were measured using a goniometer. The uninjured elbows served as controls.

At follow-up, the carrying angle in full elbow extension and the range of motion (ROM) of the elbow and forearm were measured bilaterally. We recorded clinical results as good, fair, or poor according to the range of movement (pronation, supination, flexion, extension) and the presence of pain as per the Steinberg and Rodriguez-Merchan classification.23 We also evaluated any change in the carrying angle and axial deformity. Flexion and extension of the elbow, pronation and supination of the forearm, and the valgus angle of the extended elbow were measured using a goniometer. The uninjured elbows served as controls. Radiographic evaluation documented the size of the radial head, presence of avascular necrosis, premature physeal closure and cubitus valgus. The final follow-up radiographs included standard antero-posterior and lateral radiographs of both elbows. Statistics Descriptive statistics were used for the variables of our group. The paired Student t test was used to analyze the differences between the normal elbow and the injured elbow when the data were parametric, and the Pearson correlation was used to correlate the results with the collected data. Outcome data for each group are presented as the mean and SD, and the mean difference between groups and the 95% confidence interval are provided. A P value of <0.05 was considered significant. Statistical analysis was performed using a GraphPad prism 5 computer program.

o correlate the results with the collected data. Outcome data for each group are presented as the mean and SD, and the mean difference between groups and the 95% confidence interval are provided. A P value of <0.05 was considered significant. Statistical analysis was performed using a GraphPad prism 5 computer program. Surgical Technique of Open Reduction The anconeus-extensor carpi ulnaris interval was used to expose the orbicular ligament. The radial head was gently repositioned and interposed capsular or ligamentous structures that blocked reduction were removed. Rotation can be judged by the fit of the fragments at surgery especially if there was a Salter 2 type fragment. We usually check by fluoroscopy the reduction obtained (in all cases no residual angulation or translation was observed). The head fragment was stable after reduction and internal fixation was not performed. Reduction was maintained by cast immobilization in 90-degree elbow flexion and about 45 degrees of pronation for 4 to 5 weeks.

Surgical Technique of Open Reduction The anconeus-extensor carpi ulnaris interval was used to expose the orbicular ligament. The radial head was gently repositioned and interposed capsular or ligamentous structures that blocked reduction were removed. Rotation can be judged by the fit of the fragments at surgery especially if there was a Salter 2 type fragment. We usually check by fluoroscopy the reduction obtained (in all cases no residual angulation or translation was observed). The head fragment was stable after reduction and internal fixation was not performed. Reduction was maintained by cast immobilization in 90-degree elbow flexion and about 45 degrees of pronation for 4 to 5 weeks. RESULTS Twenty-eight patients met the inclusion criteria except for the final follow-up, which 4 patients refused to take part in. Twenty-four cases satisfied all the inclusion criteria and were evaluated clinically and radiologically at a mean follow-up of 7 years and 1 month (range, 3.2 to 12.1 y). There were 11 boys and 13 girls with a median age of 7 years and 1 month (range, 4.3 to 10.2 y), the right arm was involved in 16 patients and the left in 8. (In all the 16 patients the right arm was dominant and in 4 of the 8 the left was dominant and it did not play a role in the outcome). All fractures were completely displaced without contact between the head and the radial metaphysis and had an angulation of >60 degrees (O’Brien type 3). In 4 cases, there were olecranon fractures, 2 with an associated elbow dislocation (Table 1). TABLE 1 Clinical and Radiologic Data

RESULTS Twenty-eight patients met the inclusion criteria except for the final follow-up, which 4 patients refused to take part in. Twenty-four cases satisfied all the inclusion criteria and were evaluated clinically and radiologically at a mean follow-up of 7 years and 1 month (range, 3.2 to 12.1 y). There were 11 boys and 13 girls with a median age of 7 years and 1 month (range, 4.3 to 10.2 y), the right arm was involved in 16 patients and the left in 8. (In all the 16 patients the right arm was dominant and in 4 of the 8 the left was dominant and it did not play a role in the outcome). All fractures were completely displaced without contact between the head and the radial metaphysis and had an angulation of >60 degrees (O’Brien type 3). In 4 cases, there were olecranon fractures, 2 with an associated elbow dislocation (Table 1). TABLE 1 Clinical and Radiologic Data Results were graded as good, (Fig. 1) fair, (Fig. 2) or poor (Fig. 3) as shown in Table 1. Fair (25%) and poor (20%) results were directly correlated with reduction of pronation-supination ROM (P=0.001), reduction of flexion-extension ROM (P=0.001), increase of elbow valgus angle (P=0.002), presence of necrosis of the radial head (P=0.001), premature physeal closure (Fig. 2F) (P=0.01), and an associated lesion, for example, olecranon fracture associated with or without elbow dislocation (P=0.002) (Table 2). TABLE 2 Correlation Between Steinberg and Rodriguez-Merchan Classification of the Results (1 Good, 2 Fair, 3 Poor) and Clinical and Radiologic Results

Results were graded as good, (Fig. 1) fair, (Fig. 2) or poor (Fig. 3) as shown in Table 1. Fair (25%) and poor (20%) results were directly correlated with reduction of pronation-supination ROM (P=0.001), reduction of flexion-extension ROM (P=0.001), increase of elbow valgus angle (P=0.002), presence of necrosis of the radial head (P=0.001), premature physeal closure (Fig. 2F) (P=0.01), and an associated lesion, for example, olecranon fracture associated with or without elbow dislocation (P=0.002) (Table 2). TABLE 2 Correlation Between Steinberg and Rodriguez-Merchan Classification of the Results (1 Good, 2 Fair, 3 Poor) and Clinical and Radiologic Results FIGURE 1 A and B, Radial neck fracture of the right elbow in a 6–year-old and 3-month-old girl. C and D, Postoperative radiographs after open reduction of the fracture. Radiographic result 9.1 years after treatment: E and F, Contralateral normal elbow; G and H, Operated elbow (case 13, good result). FIGURE 2 A and B, Radial neck fracture of the left elbow in a 9-year-old and 2-month-old boy. C and D, Postoperative radiographs after open reduction of the fracture. Radiographic result 3.2 years after treatment: E and F, Operated elbow: physeal premature closure of the proximal radius; G and H, contralateral normal elbow (case 4, fair result).

ck fracture of the left elbow in a 9-year-old and 2-month-old boy. C and D, Postoperative radiographs after open reduction of the fracture. Radiographic result 3.2 years after treatment: E and F, Operated elbow: physeal premature closure of the proximal radius; G and H, contralateral normal elbow (case 4, fair result). FIGURE 3 A and B, Radial neck fracture of the left elbow associated with olecranon fracture in an 8-year-old and 3-month-old boy. C and D, Radiographs after 1 year showing head necrosis, premature closure of the physis. E and F, Radiographic result after 4.1 years: severe deformity of the radial head and subluxation (case 5, poor result). Significant statistical differences were seen between the injured and normal elbow with radial head diameter (P<0.0001), valgus angle of the elbow (P<0.0001), elbow flexion-extension ROM (P<0.01) [due to the reduction of flexion which is correlated with poor results (P<0.003)], and with loss of pronation-supination ROM (P<0.0003) [the reduction of pronation and supination were both correlated with poor results (P<0.01)] (Table 3). The main cause of unsatisfactory results was a limitation in pronation-supination: 6 cases had about 20 degrees less than normal pronation-supination (Table 4; cases 2, 3, 4, 6, 7, 17) and another 5 cases had about 40 degrees less supination than normal pronation-supination (Table 4; cases 1, 5, 8, 9, 10) compared with the noninjured contralateral elbow.

ults was a limitation in pronation-supination: 6 cases had about 20 degrees less than normal pronation-supination (Table 4; cases 2, 3, 4, 6, 7, 17) and another 5 cases had about 40 degrees less supination than normal pronation-supination (Table 4; cases 1, 5, 8, 9, 10) compared with the noninjured contralateral elbow. TABLE 3 Paired t Test Between Normal and Fractured Side in Radial Head Diameter at Follow-up Antero-posterior Radiograms; Valgus Angle, Flexion-extension, Pronation-supination at Clinical Follow-up TABLE 4 Clinical and Radiologic Data at Follow-up Pain was considered intermittent and slight by 3 patients who practiced intensive sports, which involved use of the injured extremity. Four patients experienced pain and mild loss of strength (loss of strength is defined by the patient self-sensing reduction of strength or by the examiner during manual muscle testing involving tightening the examiner’s fingers) and 4 experienced pain and moderate loss of strength. On radiographic examination there was radial head enlargement of 2 to 5 mm in 90% of patients. Loss of motion was not associated with this morphologic change (P=0.08); poor outcomes were seen in 3 cases with avascular necrosis and in 7 cases with premature closure of the growth plate and residual neck deformity (Fig. 3). The main functional losses were pronation and supination and elbow flexion (Table 1; cases 1, 4, 5, 11, 17, 18).

ot associated with this morphologic change (P=0.08); poor outcomes were seen in 3 cases with avascular necrosis and in 7 cases with premature closure of the growth plate and residual neck deformity (Fig. 3). The main functional losses were pronation and supination and elbow flexion (Table 1; cases 1, 4, 5, 11, 17, 18). DISCUSSION This study reports the largest series of these fractures with a combination of significant angulation and displacement of the fracture requiring open reduction. We feel that open reduction is indicated when the head of the radius is completely displaced and without contact with the rim of the metaphysis. Even minimal contact was noted in other series to help obtain a closed reduction with a Kirschner wire or an intramedullary elastic nail. In our series, the degree of angulation was always >60 degrees and about 90 degrees in most cases. In our cases, residual radial head deformity due to premature closure of the growth plate and avascular necrosis were correlated with a functional deficit. Associated elbow injury was coupled with a negative prognosis. In our series, about 25% of patients had fair and 20% had poor results. Outcomes were good in 55% and felt to represent a better outcome than if the fracture remained nonanatomically reduced with residual angulation and/or displacement of the radial head.

. Associated elbow injury was coupled with a negative prognosis. In our series, about 25% of patients had fair and 20% had poor results. Outcomes were good in 55% and felt to represent a better outcome than if the fracture remained nonanatomically reduced with residual angulation and/or displacement of the radial head. Loss of motion, the primary cause of poor results, is felt to be secondary to a combination of loss of joint congruity and fibrous adhesions.5,7,17,20,21,24,25 Open reduction was performed to provide an anatomic reduction with minimal trauma of soft tissue around the fracture.26,2 The bloody supply of the radial head is precarious, and meticulous dissection with preservation of soft tissue attachments to the metaphyseal spike may improve the results.7 In our series, the head was repositioned as gently as possible removing interposed structures that blocked reduction. We found the head fragment to be stable after reduction and internal fixation was not performed. Complication relative to internal fixation to the fragment blood supply and particular surface was avoided without loss of reduction. Acceptability of reduction has to be related to the type of proximal fragment dislocation and displacement and age of the patient, with a younger child having greater potential of remodeling. The generally accepted upper limit of accepted angulation is 45 degrees at 10 years of age.9,11–13,17,19–21 This angular value was chosen from series that included multiple methods of treatment, limited follow-up, and, in some cases, not including the amount of fracture translation.

ing greater potential of remodeling. The generally accepted upper limit of accepted angulation is 45 degrees at 10 years of age.9,11–13,17,19–21 This angular value was chosen from series that included multiple methods of treatment, limited follow-up, and, in some cases, not including the amount of fracture translation. Different techniques are proposed to minimize iatrogenic insults to the vulnerable proximal radius. Potential insults are direct injury from percutaneous pins or cumulative trauma from repeated failed manipulations.7,13 Greater O’Brien grade, higher fracture angulation, and increased fracture displacement were associated with more invasive interventions in the series reported by Zimmerman et al.9 Certain radiographic patterns, such as laterally displaced fractures with potential annular ligament entrapment may represent higher levels of bony and soft tissue injuries as was seen in some of our cases. Recent works report that closed techniques, especially intramedullary nailing, can be successful for severely displaced fractures, but about 10% of cases still needed open reduction.20,21,27 The learning curve to gain expertise in this method is significant. Comparison with other papers on open reduction treatment was difficult, as they did not use similar classification methods of the fractures nor outcome measures at follow-up with metrics used in the current paper.

Recent works report that closed techniques, especially intramedullary nailing, can be successful for severely displaced fractures, but about 10% of cases still needed open reduction.20,21,27 The learning curve to gain expertise in this method is significant. Comparison with other papers on open reduction treatment was difficult, as they did not use similar classification methods of the fractures nor outcome measures at follow-up with metrics used in the current paper. Twelve percent of the total of 195 patients had a severe displacement and could not be treated by closed reduction. Although we did not use intramedullary nailing, the percentage of cases treated with open reduction is similar to the cases reported in studies in which the Metaizeau technique was used. The limit of the study is to be a retrospective review without comparing different methods and strategy of treatment. CONCLUSIONS In our opinion, proximal radial fractures with totally displaced proximal fragments and residual angulation, especially if associated with a lateral shift, for which closed or percutaneous reduction is not successful should be treated with open surgery. Open reduction should be performed with minimal injury to osteo-chondral, ligamentous, and muscular structures to reduce complications associated with this injury. The causes of poor results in these significant fractures appear related to the major focal trauma to the bony and soft tissues in this area. ACKNOWLEDGMENT The authors would like to thank Professor Emeritus Carl Stanitski, from MUSC University of South Carolina, for his supervision.

Open reduction should be performed with minimal injury to osteo-chondral, ligamentous, and muscular structures to reduce complications associated with this injury. The causes of poor results in these significant fractures appear related to the major focal trauma to the bony and soft tissues in this area. ACKNOWLEDGMENT The authors would like to thank Professor Emeritus Carl Stanitski, from MUSC University of South Carolina, for his supervision. These authors contributed equally. None of the authors have received any funding or economical support for this study. The authors declare no conflicts of interest.

This is a prospective cohort controlled study of nighttime bracing versus no treatment for adolescent idiopathic scoliosis (AIS) in young girls with mild curves. In 1 institution, premenarchal, Risser 0 girls with primary scoliotic curves between 15 and 25 degrees were treated with nighttime Charleston bending brace until skeletal maturity and in another center were observed until progression to standard bracing criteria. We hypothesize that (a) this patient population is at high risk for curve progression and (b) that nighttime bracing using a Charleston bending brace is effective in preventing progression of smaller curves (15 to 25 degrees) in skeletally immature, premenarchal female patients relative to current standard of care (observation for curves <25 degrees) to prevent the need for fulltime bracing.

progression and (b) that nighttime bracing using a Charleston bending brace is effective in preventing progression of smaller curves (15 to 25 degrees) in skeletally immature, premenarchal female patients relative to current standard of care (observation for curves <25 degrees) to prevent the need for fulltime bracing. Spinal bracing is widely utilized in patients with moderate severity AIS with the goal of preventing curve progression and therefore preventing the need for surgical correction.1 The generally accepted parameters for initiation of brace treatment in AIS coincide with the Scoliosis Research Society criteria for standardization of bracing studies. These criteria are: primary curve angle between 25 and 40 degrees, age over 10 when brace is prescribed, Risser sign 0 to 2, <1-year postmenarchal, and no prior treatment.2 Despite the presence of these criteria for the last 15 years, there remains a significant debate with regard to the efficacy of bracing and a paucity of high-quality studies to show efficacy.3 Furthermore, many different brace designs exist with conflicting evidence on their relative efficacy.1,4–9

no prior treatment.2 Despite the presence of these criteria for the last 15 years, there remains a significant debate with regard to the efficacy of bracing and a paucity of high-quality studies to show efficacy.3 Furthermore, many different brace designs exist with conflicting evidence on their relative efficacy.1,4–9 AIS is well documented to progress most rapidly during the pubertal growth spurt, and if bracing is to be effective in preventing progression than it must be prescribed during this period of rapid growth. This serves as the basis for the SRS guidelines to target the patient population with the most potential benefit. However, peak growth velocity occurs during menarche, before radiographic appearance of the iliac apophysis. Although including recently postmenarchal Risser 1 and 2 patients allows for larger study size, there is concern that progression rates may be highest in the premenarchal, Risser 0 population and these patients may benefit from early intervention even with small curves at presentation.

ppearance of the iliac apophysis. Although including recently postmenarchal Risser 1 and 2 patients allows for larger study size, there is concern that progression rates may be highest in the premenarchal, Risser 0 population and these patients may benefit from early intervention even with small curves at presentation. The Charleston brace is a nighttime-only bending brace that has been shown to be effective in controlling curve progression in multiple studies.8–12 Biomechanical analysis has shown that significant compressive stress relayed to the spine on the convexity of the scoliotic curve tensile stress on the concavity.13 This may allow for growth modulation during spinal growth and contribute to efficacy. Furthermore, the psychosocial effects of bracing on the AIS population are significant and nighttime-only brace wear may improve patient acceptance and compliance with treatment, although this has not been definitively shown.14,15

.13 This may allow for growth modulation during spinal growth and contribute to efficacy. Furthermore, the psychosocial effects of bracing on the AIS population are significant and nighttime-only brace wear may improve patient acceptance and compliance with treatment, although this has not been definitively shown.14,15 METHODS Premenarchal, Risser 0 female patients presenting to 2 pediatric orthopaedic specialty practices for evaluation of idiopathic scoliosis with Cobb angle measurements between 15 and 25 degrees were identified for inclusion in the study. Informed consent was obtained. Patients were excluded for prior treatment (bracing or surgery), nonidiopathic etiology, or unwillingness to participate in the study. Assignment to treatment versus control arms was determined by location of presentation. All patients from the treatment group site were assigned to nighttime bracing with the Charleston bending brace at the time of presentation and all patients from the control site were assigned to observation at initial presentation. Patients were followed up at approximately 6-month intervals with full-standing posteroanterior scoliosis radiographs taken at each visit. An additional visit shortly after initiation of brace treatment (if braced) was performed to check brace fit and curve correction with in-brace radiographs. Curve magnitude, Risser sign, menarchal status, and self-reported percentage of brace wear compliance (if braced) were recorded at each visit. The treating physician recorded the measurements and was unaware of whether the patient was enrolled in the study. All radiographs were reviewed by a research fellow and any discrepancy >3 degrees was submitted to a reviewer who made the final determination. In the control group, fulltime TLSO bracing was instituted if progression to 25 degrees Cobb angle or over 5 degrees was observed and this was continued until skeletal maturity. In the treatment group, nighttime Charleston bracing was continued through skeletal maturity. Addition of daytime TLSO brace wear was recommended for curves progressing past 25 degrees despite nighttime bracing. They were maintained in the Charleston brace at night with or without daytime TLSO wear. Surgical intervention was offered in both groups at the discretion of the treating surgeon if the curve progressed to surgical magnitude (>50 degrees). Patients were followed up to skeletal maturity and minimum follow-up was 2 years.

ey were maintained in the Charleston brace at night with or without daytime TLSO wear. Surgical intervention was offered in both groups at the discretion of the treating surgeon if the curve progressed to surgical magnitude (>50 degrees). Patients were followed up to skeletal maturity and minimum follow-up was 2 years. All patients were analyzed regardless of compliance (intent-to-treat). Data were analyzed for comparability of treatment groups, progression to fulltime bracing threshold (25 degrees), progression over 5 and 10 degrees of primary curve Cobb angle magnitude during the treatment period, and progression to surgical intervention. Two-sample t test was used to analyze for difference between groups for continuous variables and the 1-tail Fisher exact test was used for binary variables. Curve type was not analyzed due to insufficient sample size. Compliance data were not analyzed due to the proven unreliability of self-reported compliance data.

n. Two-sample t test was used to analyze for difference between groups for continuous variables and the 1-tail Fisher exact test was used for binary variables. Curve type was not analyzed due to insufficient sample size. Compliance data were not analyzed due to the proven unreliability of self-reported compliance data. RESULTS Twenty-three patients were enrolled in the control group and 23 in the treatment group. Of these, 9 failed to complete 2-year follow-up and were therefore excluded, leaving 16 in the control group and 21 in the treatment group for data analysis. The groups were similar at presentation (Table 1). Average curve magnitude was 19 degrees in both groups. In the control group, all patients progressed to fulltime bracing threshold (Fig. 1). Eight patients (50%) progressed >5 degrees but <10 degrees and the remaining 8 patients (50%) progressed >10 degrees. In the treatment group, 6 patients (29%) did not progress and were continued in nighttime bracing through skeletal maturity (Fig. 2). This was statistically significant (P=0.023). Four patients (19%) progressed >5 degrees but <10 degrees and the remaining 11 patients (52%) progressed >10 degrees. Two patients in the control group (12%) and 4 in the treatment group (19%) progressed to surgical intervention despite bracing. This was not statistically significant (P=0.472). TABLE 1 Group Demographics Show No Difference Between Groups at Time of Inclusion FIGURE 1 Curve progression for each patient in control group. FIGURE 2 Curve progression for each patient in treatment group.

RESULTS Twenty-three patients were enrolled in the control group and 23 in the treatment group. Of these, 9 failed to complete 2-year follow-up and were therefore excluded, leaving 16 in the control group and 21 in the treatment group for data analysis. The groups were similar at presentation (Table 1). Average curve magnitude was 19 degrees in both groups. In the control group, all patients progressed to fulltime bracing threshold (Fig. 1). Eight patients (50%) progressed >5 degrees but <10 degrees and the remaining 8 patients (50%) progressed >10 degrees. In the treatment group, 6 patients (29%) did not progress and were continued in nighttime bracing through skeletal maturity (Fig. 2). This was statistically significant (P=0.023). Four patients (19%) progressed >5 degrees but <10 degrees and the remaining 11 patients (52%) progressed >10 degrees. Two patients in the control group (12%) and 4 in the treatment group (19%) progressed to surgical intervention despite bracing. This was not statistically significant (P=0.472). TABLE 1 Group Demographics Show No Difference Between Groups at Time of Inclusion FIGURE 1 Curve progression for each patient in control group. FIGURE 2 Curve progression for each patient in treatment group. DISCUSSION This study highlights a particular subset of patients with idiopathic scoliosis that have not been well studied in an independent manner. We show a significant rate of curve progression in these Risser 0, premenarchal girls despite presenting with small magnitude curves (>15 degrees but <25 degrees). With observation, 100% of these patients progressed to standard criteria for fulltime bracing. With nighttime Charleston brace use, 29% were maintained without progression. Although the majority of patients progressed despite bracing, this still represents a significant decrease in progression. The hypothesis that nighttime Charleston bracing would reduce the need for fulltime bracing was confirmed. Rate of progression to surgical intervention was not statistically significant; however, this study did not include enough patients to make a difference in observed surgical rate meaningful. We also did not have electronically monitored braces for accurate compliance data. Although brace wear compliance is an important factor and would be helpful for determining true efficacy, we feel that the intention-to-treat model with a non–brace-wearing control group provides the most accurate assessment of the efficacy of this treatment model.

nically monitored braces for accurate compliance data. Although brace wear compliance is an important factor and would be helpful for determining true efficacy, we feel that the intention-to-treat model with a non–brace-wearing control group provides the most accurate assessment of the efficacy of this treatment model. This study purposefully does not meet the SRS criteria for brace studies. Although we agree that the SRS criteria are valuable for generating a body of literature that is relevant and helpful to elucidate the value of bracing in the typically presenting AIS patient, it is our opinion that the patient population represented in this study is at particular risk for progression and should be singled out for analysis. The high rate of progression in the control group confirms this opinion, and the inclusion of a prospective control group strengthens the study. All Risser 0, premenarchal girls presenting with curve angles from 15 to 25 degrees progressed to >25 degrees with observation alone. The high rate of progression in this specific subset of girls between 15 and 25 degrees has not been previously identified, perhaps because the previous natural history studies have included more mature patients, or immature patients with curves <15 degrees.

25 degrees progressed to >25 degrees with observation alone. The high rate of progression in this specific subset of girls between 15 and 25 degrees has not been previously identified, perhaps because the previous natural history studies have included more mature patients, or immature patients with curves <15 degrees. Both fulltime and nighttime bracing present psychosocial challenges to acceptance of treatment and compliance that were not addressed in this study. It is our opinion that nighttime bracing is better accepted by patients, as there is no stigma associated with wearing the brace to school and they are able to participate in all social and athletic activities without encumbrance. Acceptance of treatment is particularly important in this population as they are skeletally younger at the time of presentation and will require a longer period of treatment to reach skeletal maturity. It remains to be proven whether bracing will influence the need for surgery relative to natural history. In this study we had similar number of patients progress to surgical intervention regardless of treatment. On the basis of the results of this study, it is our conclusion that nighttime bracing with the Charleston brace should be considered for Risser 0, premenarchal girls with scoliosis of 15 to 25 degrees due to the high risk for progression without treatment. The authors declare no conflicts of interest.

Developmental dysplasia of the hip (DDH) is a common disorder in the pediatric population with an overall incidence of approximately 3 to 4 per 1000 live births.1 Although the clinical examination remains the mainstay for diagnosing DDH in early infancy, not all cases of DDH are detectable by physical examination. Imaging, either by ultrasonography or radiography, have become popular worldwide for screening or confirmation of the diagnosis as well as to classify the severity of the dysplasia. Quantifying the severity of displacement in DDH is useful for prognostication and clinical decision-making. In the newborn and young infant, ultrasounds are superior because the cartilaginous femoral head is not visible on radiographs. Following the appearance of the ossific nucleus in the older infant, anteroposterior (AP) pelvic radiographs replace ultrasonography as the screening imaging modality of choice. Ultrasonography has the limitation of being less accurate with continued growth and ossification of the femoral head. However, radiographic assessment may still be suboptimal or misleading when ossification of the femoral head is delayed or eccentric as in hips with DDH.

phy as the screening imaging modality of choice. Ultrasonography has the limitation of being less accurate with continued growth and ossification of the femoral head. However, radiographic assessment may still be suboptimal or misleading when ossification of the femoral head is delayed or eccentric as in hips with DDH. Several ultrasonographic and radiographic parameters have been described to define hip dysplasia. Some radiographic parameters such as the center-edge angle of Wiberg and the acetabular angle of Hilgenreiner are used to quantify subtle differences in acetabular dysplasia.2,3 In the older child, the center-edge angle of Wiberg is used to evaluate the degree of lateral femoral head coverage by the acetabulum in the frontal plane.2 The acetabular index angle of Hilgenreiner quantifies the development of the acetabulum by measuring the slope of the boney acetabulum in the frontal plane.3 However, these do not address more severe categories of dislocation for prognostic purposes before treatment. For classification of the full spectrum of severity, the Graf sub-types are well established on ultrasound, whereas the Tönnis method helps classify the severity of DDH using plain radiographs.4

frontal plane.3 However, these do not address more severe categories of dislocation for prognostic purposes before treatment. For classification of the full spectrum of severity, the Graf sub-types are well established on ultrasound, whereas the Tönnis method helps classify the severity of DDH using plain radiographs.4 The Tönnis method quantifies the severity of DDH using the relative position of the ossific nucleus to Perkin’s (P-line) and Hilgenreiner’s lines (H-line).4 This method relies on the presence of the ossification centre, which can be delayed in appearance and is often eccentrically located within the femoral head.5 These issues can therefore make the application of the Tönnis classification in the younger infant quite difficult and potentially unreliable. Despite this limitation, orthopedic surgeons around the world who treat children with DDH continue to utilize plain radiographs and the Tönnis criteria to confirm the diagnosis of DDH, to establish treatment recommendations, and to assess the effect of treatment.6,7 Recognizing the limitation of the Tönnis method in young infants, the International Hip Dysplasia Institute (IHDI) group developed a new radiographic classification system to quantify the severity of the displacement of the femoral head, which does not rely on the presence of the ossific nucleus and, therefore, can be applied to children of all ages. The aims of this study were 2-fold: (1) to test the reliability of the IHDI classification of the severity of the hip displacement in DDH both by experienced pediatric orthopedic surgeons as well as by residents in training, and (2) to compare the reliability of the IHDI method with that of the Tönnis classification.

. The aims of this study were 2-fold: (1) to test the reliability of the IHDI classification of the severity of the hip displacement in DDH both by experienced pediatric orthopedic surgeons as well as by residents in training, and (2) to compare the reliability of the IHDI method with that of the Tönnis classification. METHODS The proposed IHDI classification uses the position of the proximal femoral metaphysis (instead of the ossific nucleus) as the important reference landmark to determine the location of the hip. We define the H-point as the midpoint of the superior margin of the ossified metaphysis. As with the Tönnis system, H-line is drawn through the top of the tri-radiate cartilages bilaterally. The standard P-line is then drawn perpendicular to the H-line at the superolateral margin of the acetabulum. Unlike previous classification systems, an additional diagonal line (D-line) is then drawn 45 degrees from the junction of H-line and P-line. The position of the H-point then determines the IHDI grade. In an IHDI grade I hip, the H-point is at or medial to the P-line. In grade II, the H-point is lateral to the P-line and at or medial to the D-Line. For grade III, the H-point is lateral to the D-line and at or inferior to the H-line. Finally, in grade IV hips, the H-point is superior to the H-line (Table 1, Fig. 1). TABLE 1 Radiographic Measurements for IHDI Classification

METHODS The proposed IHDI classification uses the position of the proximal femoral metaphysis (instead of the ossific nucleus) as the important reference landmark to determine the location of the hip. We define the H-point as the midpoint of the superior margin of the ossified metaphysis. As with the Tönnis system, H-line is drawn through the top of the tri-radiate cartilages bilaterally. The standard P-line is then drawn perpendicular to the H-line at the superolateral margin of the acetabulum. Unlike previous classification systems, an additional diagonal line (D-line) is then drawn 45 degrees from the junction of H-line and P-line. The position of the H-point then determines the IHDI grade. In an IHDI grade I hip, the H-point is at or medial to the P-line. In grade II, the H-point is lateral to the P-line and at or medial to the D-Line. For grade III, the H-point is lateral to the D-line and at or inferior to the H-line. Finally, in grade IV hips, the H-point is superior to the H-line (Table 1, Fig. 1). TABLE 1 Radiographic Measurements for IHDI Classification FIGURE 1 IHDI classification for DDH (not requiring the presence of an ossific nucleus). H-line is Hilgenreiner’s line drawn through the top of the tri-radiate cartilages bilaterally. P-line is Perkin’s line drawn perpendicular to the H-line at the superolateral margin of the acetabulum. D-line is diagonal line drawn 45 degrees from the junction of H-line and P-line. H-point is the midpoint of the superior margin of the ossified metaphysis. Grade I: the H-point is at or medial to the P-line. Grade II: the H-point is lateral to the P-line and at or medial to the D-line. Grade III: the H-point is lateral to the D-line and at or inferior to the H-line. Grade IV: the H-point is superior to the H-line.

idpoint of the superior margin of the ossified metaphysis. Grade I: the H-point is at or medial to the P-line. Grade II: the H-point is lateral to the P-line and at or medial to the D-line. Grade III: the H-point is lateral to the D-line and at or inferior to the H-line. Grade IV: the H-point is superior to the H-line. To test the reliability of the classification system, a purposeful sample of antero-posterior pelvis radiographs of 20 children with untreated DDH across a wide age spectrum from 3 months to 32 months (mean age: 10 mo) were selected by the senior author who was not involved in the reliability assessment. The selected sample included both unilateral and bilateral involvement and a spectrum of severity. All radiographs selected were before any treatment. The radiographs were then analyzed by 8 independent observers who were blinded to the measurements of each other and to the identity of the patients. Observers included: (1) 6 consultant pediatric orthopedic surgeons with a special interest in pediatric hip surgery, (2) 2 orthopedic senior residents who had completed 6 months on a pediatric orthopedic rotation. Any patient identifying information was removed from all radiographs.

and to the identity of the patients. Observers included: (1) 6 consultant pediatric orthopedic surgeons with a special interest in pediatric hip surgery, (2) 2 orthopedic senior residents who had completed 6 months on a pediatric orthopedic rotation. Any patient identifying information was removed from all radiographs. All observers were asked to classify both hips on each radiograph with both the Tönnis method (Fig. 2) as well as the IHDI method. Radiographs were supine AP views of the pelvis that were obtained with the hips at rest and with lower limbs held gently (without traction) in the neutral position with the patellae facing forward. Radiographic landmarks in the Tönnis and IHDI methods were defined based on the classic descriptions of these specific parameters from the literature. The technique for each radiographic parameter was agreed upon by the observers a priori, to minimize errors in marking of the landmarks, (ie, drawing the lines) necessary for each classification. For the IHDI classification, it was agreed that an H-point that fell on a line would be scored as the lower grade. In addition, a standardized transparent measurement tool was provided to each observer to aid in the marking of landmarks (Fig. 3).

the landmarks, (ie, drawing the lines) necessary for each classification. For the IHDI classification, it was agreed that an H-point that fell on a line would be scored as the lower grade. In addition, a standardized transparent measurement tool was provided to each observer to aid in the marking of landmarks (Fig. 3). FIGURE 2 Tönnis classification for DDH (relies on the location of the ossific nucleus).4 Grade I: the ossification center of the capital epiphysis is medial to the perpendicular line from the superolateral margin of the acetabulum (Perkins’s line). Grade II: the ossification center of the capital epiphysis is lateral to the Perkin’s line, but below the superolateral margin of the acetabulum (SMA-line). Grade III: the ossification center is at the level of the superolateral margin of the acetabulum. Grade IV: the ossification center is above the superolateral margin of the acetabulum. FIGURE 3 Transparent measurement tool provided to each observer.

FIGURE 2 Tönnis classification for DDH (relies on the location of the ossific nucleus).4 Grade I: the ossification center of the capital epiphysis is medial to the perpendicular line from the superolateral margin of the acetabulum (Perkins’s line). Grade II: the ossification center of the capital epiphysis is lateral to the Perkin’s line, but below the superolateral margin of the acetabulum (SMA-line). Grade III: the ossification center is at the level of the superolateral margin of the acetabulum. Grade IV: the ossification center is above the superolateral margin of the acetabulum. FIGURE 3 Transparent measurement tool provided to each observer. Statistical Analysis Statistical analyses were performed utilizing SPSS software (version 12, IBM; Armonk, NY). Intra observer and interobserver reliability for each measure was assessed using intraclass correlation coefficient (ICC).8 The ICC reports a value between 0.0 and 1.0, where 1.0 represents perfect agreement or concordance. Although there are no definitive values that clearly differentiate between acceptable and unacceptable agreement, for the purposes of this study we have adopted Munro’s correlation strength categories (0.9-1.0=“very high”; 0.7-0.89=“high”; 0.5-0.69=“moderate”; 0.26-0.49=“low”; 0.0-0.25= “little if any”).9 The 2-way mixed model (absolute agreement) was utilized as the observers in this study were not randomly selected and were measuring identical radiographs.

dy we have adopted Munro’s correlation strength categories (0.9-1.0=“very high”; 0.7-0.89=“high”; 0.5-0.69=“moderate”; 0.26-0.49=“low”; 0.0-0.25= “little if any”).9 The 2-way mixed model (absolute agreement) was utilized as the observers in this study were not randomly selected and were measuring identical radiographs. RESULTS All 20 radiographs (40 hips) were classifiable by the IHDI method by all the raters (6 consultant pediatric orthopaedic surgeons and 2 senior orthopedic residents) (Figs. 4A–D). Ten of the 40 (25%) hips could not be classified by the Tönnis method because of the absence of the ossific nucleus, although some raters provided a Tönnis grade based on their assumption of the location of the ossific nucleus. FIGURE 4 (A) Case example of an anteroposterior (AP) pelvic radiograph of an infant with DDH. The right hip was classified as an IHDI grade I hip, whereas the left hip was classified as grade III. (B) Case example of an AP pelvic radiograph of another infant with bilateral DDH. The right hip was classified as an IHDI grade III hip, whereas the left hip was classified as grade II. (C) Third case example of an AP pelvic radiograph of an infant with DDH. The right hip was classified as an IHDI grade III hip, whereas the left hip was classified as grade II. (D) Final case example of an AP pelvic radiograph of an infant with bilateral DDH. Both hips were classified as IHDI grade IV. Note that all hips in the case examples could be classified, although the ossific nucleus was variably present.

We are aware of 3 published radiographic methods for evaluation of DDH severity at time of diagnosis. One is the method of Yamamuro and Chene10 that measures the distance from the center of the metaphysis to the H-line and the distance between the center of the metaphysis and the medial wall of the acetabulum (Fig. 5). Although this measurement has been proven reliable, it is a continuous variable that has not been divided into categories for comparative purposes. FIGURE 5 Yamamuro measurement method. Y indicates Y-line; A, Yamamuro-A; B, Yamamuro-B; H, Hilgenreiner-H; D, Hilgenreiner-D; h/b and c/b ratio, Smith’s ratio for superior and lateral displacement. Reproduced with permission from Boniforti et al.14 Dyson et al11 described a method of relating the position of the proximal femoral metaphysis to the acetabulum using the metaphyseal-edge (ME) angle. The ME angle is subtended between P-line and a line drawn from the medial border of the upper femoral metaphysis to the lateral edge of the bony acetabulum. The ME angle is positive if the medial edge of the upper femoral metaphysis lies medial to the lateral edge of the bony acetabulum and negative if it lies lateral to it. In their study, a negative ME angle always indicated a dislocation. Although this system accounts for the presence of an unossified epiphysis, like the method of Yamamuro it does not provide categories of more severe dislocations for comparative purposes.

ge of the bony acetabulum and negative if it lies lateral to it. In their study, a negative ME angle always indicated a dislocation. Although this system accounts for the presence of an unossified epiphysis, like the method of Yamamuro it does not provide categories of more severe dislocations for comparative purposes. The final, and most widely used, classification was developed by the Commission for the Study of Hip Dysplasia of the German Society of Orthopedics and Traumatology as reported by Tönnis, and commonly called the Tönnis Classification.4,12 The Tönnis method of classifying DDH has been reported to be prognostic. Rosen et al13 performed measurements and statistical analysis of initial radiographs, the 1-year follow-up radiographs, and the most recent radiographs of 81 patients (103 hips) to determine, which measurements could predict the success of treatment. The average follow-up was 49 months (range, 12 to 139 mo), and the average age of the patients at the last follow-up was 65 months (range, 15 to 190 mo). Analysis of the data showed that the measurement with statistically significant predictive value was the Tönnis grade of dislocation determined from the initial radiograph. A single unit increase in the Tönnis grade was associated with a doubling of the odds of failure in patients treated with a Pavlik harness (P<0.04, odds ratio=2.2) or closed reduction (odds ratio=2.0).

statistically significant predictive value was the Tönnis grade of dislocation determined from the initial radiograph. A single unit increase in the Tönnis grade was associated with a doubling of the odds of failure in patients treated with a Pavlik harness (P<0.04, odds ratio=2.2) or closed reduction (odds ratio=2.0). A major limiting factor of the Tönnis system is that it requires the presence of an ossific nucleus of the femoral head on the plain radiograph. Rosen et al13 applied the Tönnis method to newborn infants and others without the ossification center, but the participants in the current study were unable to reliably classify hips by the Tönnis method before ossification of the femoral head. Eccentric position or delayed appearance of the ossific nucleus is a common finding in DDH, particularly in infants aged 6 to 18 months. As this is a common age of presentation in the authors’ practices, the need for a more accurate classification system remains. The Yamamura method of quantifying lateral and proximal displacement of the femoral head was validated by Boniforti and colleagues.10,14 A study by Kitoh et al15 evaluated the prognostic value of the Yamamura method for infants treated with the Pavlik harness. These authors found that the Pavlik harness was more likely to be successful when the distance from H-line to the center of the metaphysis was >6 mm. No other authors have evaluated the prognostic significance of the Yamamura method.

e prognostic value of the Yamamura method for infants treated with the Pavlik harness. These authors found that the Pavlik harness was more likely to be successful when the distance from H-line to the center of the metaphysis was >6 mm. No other authors have evaluated the prognostic significance of the Yamamura method. Although the Tönnis and Yamamura methods have been found useful, neither provides categories of classification that are easily and equally applicable whether the ossification center is present or absent. The purpose of this study was to propose a simple radiographic classification system independent of the ossific center that is reliable both in the hands of experts and novices. In this study, we demonstrated “high” to “very-high” interobserver reliability for DDH classification by the IHDI system, which was superior to the interobserver reliability of the Tönnis method, as performed by 6 pediatric orthopedic surgeons and 2 orthopedic senior residents. There were no significant differences between the ICCs of the 6 attending pediatric orthopedic surgeons versus the 2 trainees. Furthermore, the Tönnis method could not be used to classify 10 of the hips in this sample, because the ossific nucleus was not visible. In contrast, the IHDI method could be applied in these patients, proving its applicability to infants and children of all ages.

ng pediatric orthopedic surgeons versus the 2 trainees. Furthermore, the Tönnis method could not be used to classify 10 of the hips in this sample, because the ossific nucleus was not visible. In contrast, the IHDI method could be applied in these patients, proving its applicability to infants and children of all ages. It is difficult to accurately measure 3-dimensional pelvic abnormalities on a frontal plane radiograph, especially when important pelvic landmarks have yet to ossify. The greatest variability can occur in identifying the center of the minimally ossified femoral head as well as the lateral margin of the acetabulum. The location of the H-point, however, was consistent in this cohort, because the femoral metaphysis could be well defined radiographically. This further strengthens the argument that femoral metaphysis is a more reliable and consistent landmark in all children with DDH, irrespective of age and progress of ossification of femoral head. One limitation of this study was the potential for selection bias by overrepresenting hips without an ossification center in the selected sample for comparing the 2 grading systems. To minimize this risk, the sample was selected by an investigator who was not involved in the reliability grading and was based on inclusion of a wide range of severity and ages at presentation (range, 3 to 32 mo; mean, 10 mo) and not on the presence or absence of the ossific nucleus.

r comparing the 2 grading systems. To minimize this risk, the sample was selected by an investigator who was not involved in the reliability grading and was based on inclusion of a wide range of severity and ages at presentation (range, 3 to 32 mo; mean, 10 mo) and not on the presence or absence of the ossific nucleus. The main limitation of the IHDI classification system is its 2-dimensional/single plane assessment obtained from one AP view of the pelvis. In the era of advanced imaging, including the ability to three dimensionally assess the bony and soft-tissue morphology with nonradiation-based ultrasound technology, it is likely that there will be options available in the future to move from traditional biplanar radiographs to nonradiation, nonanesthesia-based dynamic 3-dimensional assessments, which could allow for a more reproducible assessment of hip dysplasia.

ft-tissue morphology with nonradiation-based ultrasound technology, it is likely that there will be options available in the future to move from traditional biplanar radiographs to nonradiation, nonanesthesia-based dynamic 3-dimensional assessments, which could allow for a more reproducible assessment of hip dysplasia. If significant variability exists between observers, or between time periods for a single observer, it is difficult to create clinical pathways to treat children with DDH and determine the impact of a certain treatment method over time. Having a simple, reliable classification that has good interobserver reproducibility and is simple to teach and use, can be invaluable in the management of this condition. Regardless of its limitations, we believe that the new IHDI classification has potentially greater utility in light of its superior reliability and wider applicability across all ages. A future goal of the IHDI is to conduct a prospective multicenter longitudinal study to establish the validity and utility of this classification system both for the purpose of prognostication and for clinical decision making in the management of DDH. ACKNOWLEDGMENT The authors thank Allison Crepeau, Patrick Wright, James Kasser, Scott Mubarak, Pablo Castañeda, and John Wedge for their contributions to the reliability grading. No authors received support for this study. The authors declare no conflicts of interest.

The American Academy of Orthopaedic Surgeons (AAOS) Outcomes Studies Committee, collaborating with the Council of Musculoskeletal Specialty Societies and the Pediatric Orthopaedic Society of North America, developed a pediatric functional outcomes assessment instrument aimed at assessing individuals with a musculoskeletal disorder.1 The Pediatric Outcomes Data Collection Instrument (PODCI) was designed as a questionnaire for children aged 2 to 18 years to collect patient-based data for both clinical assessment of treatment effectiveness and musculoskeletal research by evaluating function and quality of life (QOL). In 2002, Hunsaker et al,2 described the normative values from the general population for the PODCI subscales, Upper Extremity Function (UE), Transfers and Basic Mobility (TBM), Sports and Physical Function (SPF), Comfort, Happiness, and Global. Hunsaker reported that standardized scaled scores for specified age, sex, ethnicity, and comorbidity were available through AAOS. Unfortunately, these scores are not available (personal written communication, K. Hitchcock, 2009). There are few published values for PODCI scoring for assessing outcomes in pathologic processes for age or consideration of health/comorbidity.3–6 With restricted ability to match PODCI scores by PODCI norms for age and sex,7–10 comparative values for comorbidities, age, and sex are needed to evaluate treatment outcomes. Further evaluation is needed to determine whether sex, age, and comorbid conditions influence PODCI outcome scores.

on of health/comorbidity.3–6 With restricted ability to match PODCI scores by PODCI norms for age and sex,7–10 comparative values for comorbidities, age, and sex are needed to evaluate treatment outcomes. Further evaluation is needed to determine whether sex, age, and comorbid conditions influence PODCI outcome scores. Comparison of pretreatment and posttreatment clinical data, with normative data from the general population, is important to assess whether findings in individuals before treatment are different from population norms or come closer to normative ranges of functioning after treatment. In considering the clinical importance of treatment-outcome studies, Kendall et al11 raised 2 basic questions. First, is the pretreatment to posttreatment change large enough to be considered relevant? Second, can treated individuals be distinguished from “normal individuals” serving as a reference group? Clinical measures address the first question, whereas normative comparisons address issues of severity compared with data from a normal, age-adjusted, and sex-adjusted population. Hunsaker’s group noted a need for scores in different ages and sex to assess for normal values.2

individuals” serving as a reference group? Clinical measures address the first question, whereas normative comparisons address issues of severity compared with data from a normal, age-adjusted, and sex-adjusted population. Hunsaker’s group noted a need for scores in different ages and sex to assess for normal values.2 Comorbid or health conditions may also affect changes in PODCI scores or be associated with lower outcomes scores.1,12 The PODCI has been reported in the literature assessing children and adolescents with a wide variety of disorders from scoliosis7,10 to cerebral palsy (CP).13–18 When assessing functional outcomes in children, functional levels may not only be affected by growth and maturity factors, but also by other illnesses or conditions that may impact daily life. The increased focus of the International Classification of Function, Disability, and Health to consider a more holistic picture of the impact of medical conditions on an affected individual has made clear the need to consider other factors. Assessing functional outcomes of participation in the community, as opposed to assessing body structure and function measures in the health care setting, necessitates including other factors influencing function. Without a database of PODCI norms to compare with the PODCI outcomes for children with comorbidities, reported PODCI outcomes are incomplete.

articipation in the community, as opposed to assessing body structure and function measures in the health care setting, necessitates including other factors influencing function. Without a database of PODCI norms to compare with the PODCI outcomes for children with comorbidities, reported PODCI outcomes are incomplete. Assessments of QOL using various outcomes instruments have demonstrated patterns of responses that vary with age,1,3,19 sex,3,20 type of scales (physical observation, functional scales, or psychosocial scales),21 a particular condition being assessed,1,22 health of respondent,23 and severity of involvement with the particular condition or conditions.23,24 The purpose of this study was to establish the mean and SD for PODCI subscales on the basis of sex, age, and scores reflecting health conditions in a generalized population. To further explore the PODCI, we hypothesized that sex, age, and health/comorbid conditions would affect PODCI outcome scores.

or conditions.23,24 The purpose of this study was to establish the mean and SD for PODCI subscales on the basis of sex, age, and scores reflecting health conditions in a generalized population. To further explore the PODCI, we hypothesized that sex, age, and health/comorbid conditions would affect PODCI outcome scores. METHODS PODCI Instrument The PODCI was designed to assess the degree to which a patient’s condition or conditions affect his or her physical and emotional functioning, self-image, and symptom status. Three versions of the PODCI include: a questionnaire for children (completed by parents of children under the age of 11) and 2 surveys for adolescents (1 completed by adolescents aged 11 and older and 1 by a parent of that adolescent). Adolescent responses can be matched and compared with parent proxy surveys. The PODCI subscales comprise the following fields: UE, TBM, SPF, Comfort, Happiness, and Global. The PODCI also includes a comorbidity scale with the following health conditions: arthritis, anorexia or bulimia, asthma, attention or behavioral problems, chronic allergies or sinus trouble, developmental delay, mental retardation, diabetes, epilepsy, hearing impairment, learning problems, vision problems, speech problems, sleep problems, and/or heart problems. The respondent answers 3 health condition questions: (1) “Have you (or your child) ever had the problem?” (CM1); (2) “Do you (or your child) receive treatment for it now?” (CM2); and (3) “Does it limit your (your child’s) activity now?” (CM3). Comorbidity subscales and a comorbidity index (CMIndex) that computes an average of the responses are calculated.1

ion questions: (1) “Have you (or your child) ever had the problem?” (CM1); (2) “Do you (or your child) receive treatment for it now?” (CM2); and (3) “Does it limit your (your child’s) activity now?” (CM3). Comorbidity subscales and a comorbidity index (CMIndex) that computes an average of the responses are calculated.1 PODCI Database From AAOS The PODCI AAOS database reported by Hunsaker2 was obtained (with assistance of James Dewey, Mark Kosinski, John Ware, and Michael Goldberg) to evaluate PODCI outcomes in a generalized population sample, which includes subgroups with and without reported health conditions. The PODCI instrument was 1 of 11 musculoskeletal outcome measures evaluated for reliability and reporting normative data. A panel methodology matched US respondents recruited by the National Family Opinion to the 1998 US Census data on geographical region, age, income, household size, and reported comorbidities.2 The Internal Review Board for this institution reported that this secondary data analysis did not meet the criteria for human subjects’ research.

y matched US respondents recruited by the National Family Opinion to the 1998 US Census data on geographical region, age, income, household size, and reported comorbidities.2 The Internal Review Board for this institution reported that this secondary data analysis did not meet the criteria for human subjects’ research. Data Analysis The AAOS database with complete data on the PODCI parent version was used in this study (n=5300). Children identified as having no current or past history of health conditions were compared with children with a health condition in order to verify that the groups have the same stratification as the 1998 census. The data were taken from the CM1 question asking whether the child had ever had a health condition. A χ2 analysis showed no difference in the stratification of the children with or without health conditions with respect to race, sex, and parent version of the PODCI. The sample does not appear to be further stratified by the subgroup of current limiting comorbidities (CM3).

r the child had ever had a health condition. A χ2 analysis showed no difference in the stratification of the children with or without health conditions with respect to race, sex, and parent version of the PODCI. The sample does not appear to be further stratified by the subgroup of current limiting comorbidities (CM3). PODCI subscale scores reflected a typical healthy population with higher scores characteristic of better health. Subscale scores demonstrated significant skewness and kurtosis and were transformed to meet the assumptions for analyses. A 1-way multivariate analysis of variance (MANOVA) was conducted to determine whether there was a significant group difference in the prior health condition versus no prior health condition with respect to the dependent variables of the following parent-reported PODCI subscales: UE, TBM, SPF, Comfort, and Happiness scales. Using the Bonferroni method (with a test at P<0.01) to control for Type I error, an analysis of variance (ANOVA) was conducted on each dependent variable as a follow-up to the MANOVA. The eta squared, η2, in the ANOVA reported the proportion of the variance in the PODCI subscale score explained by the comorbid group. Further analysis of health conditions used an independent samples t test to evaluate whether the means of the PODCI subscales for the 2 independent groups, children with a currently limiting health condition (CM3) versus those children who had an identified health condition in the past (CM1), are significantly different from each other. We also used independent samples t tests to investigate whether PODCI scores differed between the sex of children and whether the sex of children within the subgroups of children with and without a health condition had mean group differences. A multiple line graph of PODCI subscale means by age for children with and without health conditions was constructed to further review the effects of age on the PODCI. As a retrospective database analysis, power was not calculated a priori, and a postevaluation power analysis is not recommended.25 The sample size is considered large compared with other studies of the PODCI. Statistical analysis was performed using SPSS (version 21.0; IBM Corp., Armonk, NY). Significance was set at P<0.05.

retrospective database analysis, power was not calculated a priori, and a postevaluation power analysis is not recommended.25 The sample size is considered large compared with other studies of the PODCI. Statistical analysis was performed using SPSS (version 21.0; IBM Corp., Armonk, NY). Significance was set at P<0.05. RESULTS The most common heath conditions reported by parents were allergy and sinus, asthma, attention/behavioral problems, sleep disturbances, and learning problems (Table 1). With respect to the evaluation of group differences in health conditions, the MANOVA revealed that the combined PODCI subscales were significantly related to whether children ever had a health condition (F5,5043=59.89, P<0.001, multivariate η2=0.056) (descriptive statistics of the PODCI by age, sex, and comorbidities are reported in Appendices 1–3, Supplemental Digital Contents 1–3, http://links.lww.com/BPO/A18, http://links.lww.com/BPO/A19, http://links.lww.com/BPO/A20). For the MANOVA, the η2 suggests that 5.6% of the variance in the PODCI subscale scores was explained by the independent variable, prior health condition or no prior health condition. Subsequent analyses revealed that children with a current or prior health condition experienced lower scores than children without a health condition on the following subscales: TBM (F1,5047=1.82, P<0.001, partial η2=0.005), SPF (F1,5047=16.69, P<0.001, partial η2=0.018), Comfort (F1,5047=29.749, P<0.001, partial η2=0.027), and Happiness (F1,5047=33.85, P<0.001, partial η2=0.035). Significant differences did not emerge for the UE subscale (F1,5047=0.003, P<0.896, partial η2=0.000). Further examination of the group that ever had a health condition (CM1) compared with the group with a currently limiting health condition (CM3) found that children with a current health condition had significantly lower scores on all PODCI subscales (Table 2). With the evaluation of sex and child health conditions, both boys and girls with health conditions had significantly lower subscale scores except for the PODCI UE subscale (Table 3). In terms of child sex differences, boys had significantly higher scores on the PODCI subscale scores of Comfort and Happiness, and no sex differences in scores were found for the other subscales (Table 4).

d girls with health conditions had significantly lower subscale scores except for the PODCI UE subscale (Table 3). In terms of child sex differences, boys had significantly higher scores on the PODCI subscale scores of Comfort and Happiness, and no sex differences in scores were found for the other subscales (Table 4). Through the evaluation of age and health conditions, age effects showed an initial increase in the subscales for groups both with and without health conditions and a varied plateau of scores, with decreases in the pain and happiness scales as age increased (Figs. 1, 2). TABLE 1 Comorbidities in AAOS Database as Reported by Parent TABLE 2 Independent Samples t Test to Compare “Ever Had Comorbidity” with “Currently Limiting Comorbidity” in the AAOS Database PODCI Subscales by Parent Response TABLE 3 Independent Samples t Test to Compare Sex in the AAOS Database PODCI Subscales by Comorbidity, Ever Had Versus No Comorbidity TABLE 4 Independent Samples t Test to Compare Sex in the AAOS Database PODCI Subscales FIGURE 1 Parent response to PODCI subscales by age for children with no comorbidities. FIGURE 2 Parent response to PODCI subscales by age for children with comorbidities.

TABLE 3 Independent Samples t Test to Compare Sex in the AAOS Database PODCI Subscales by Comorbidity, Ever Had Versus No Comorbidity TABLE 4 Independent Samples t Test to Compare Sex in the AAOS Database PODCI Subscales FIGURE 1 Parent response to PODCI subscales by age for children with no comorbidities. FIGURE 2 Parent response to PODCI subscales by age for children with comorbidities. DISCUSSION Although the PODCI has been reported to be a valid and reliable instrument,1,2 PODCI scores should still be considered within the context of sex, age, and reported comorbid conditions. Further evaluation is needed to determine whether the increase in PODCI scores with age could be based on a natural history of improvement in function over time and how children with comorbidities fit into this growth pattern. The typical rate of increase with age in function in certain diagnoses might be shown to be different from the rate in the general population, implying delays in development.26,27 Gait analysis of children with CP has shown improvement up to a point with a plateau effect and even decline in adolescence.28,29 The QOL indices, comfort and happiness, were significantly affected by the sex of the child and showed a decrease in scores in adolescence. Knowing progression of rates in normative group functions allows comparison of functional progression in groups with musculoskeletal disorders.

nd even decline in adolescence.28,29 The QOL indices, comfort and happiness, were significantly affected by the sex of the child and showed a decrease in scores in adolescence. Knowing progression of rates in normative group functions allows comparison of functional progression in groups with musculoskeletal disorders. Incomplete PODCI responses have been reported in the youngest children (ages 2 to 5), which may be due to the response structure. Daltroy et al1 reported that responses were scored as incomplete, especially on the UE or SPF, because the child had not met a milestone (even if “normal” for that age). When adjusting for other health factors, only the UE scale showed age bias. Controlling for age and comorbid conditions in comparing PODCI scores was strongly recommended. The level of function on PODCI subscales changes with age, as well as with health conditions versus without health conditions. The finding that the parent’s report of the child ever having had a comorbid condition may affect function suggests that the assessment method is valid. When a parent reports that a child is currently limited by a health/comorbid condition, the child demonstrates more limitation than those ever having had a health condition. This finding indicates that there is discriminative ability inherent in the scales. Although the health conditions may vary in severity and are not necessarily medically diagnosed, there is clearly statistical evidence that the ratings are meaningful.

rates more limitation than those ever having had a health condition. This finding indicates that there is discriminative ability inherent in the scales. Although the health conditions may vary in severity and are not necessarily medically diagnosed, there is clearly statistical evidence that the ratings are meaningful. Consideration of comorbidity scores has been suggested when assessing a patient group using the PODCI.1 Nevertheless, only a few articles have reported on comorbidities.12,14,30 A comparison group will be helpful in assessing children with musculoskeletal conditions, if the comorbidities of those groups are measured and compared with the data reported here. As early as 1970, Feinstein31 noted the importance of considering comorbid conditions when comparing groups of patients or interventions. Further evaluation of the limitations of function in patient groups should include the relationship of the limitation with their musculoskeletal condition or associated medical factors.

early as 1970, Feinstein31 noted the importance of considering comorbid conditions when comparing groups of patients or interventions. Further evaluation of the limitations of function in patient groups should include the relationship of the limitation with their musculoskeletal condition or associated medical factors. The child’s sex may also influence the PODCI score as seen in Sheffler et al’s9 study of prosthetic use and parent-child–reported PODCI scores.9 Sex of the child had an impact on parent and self-scores, with the parents of sons scoring greater on comfort than did the boys themselves. Parents rated their daughters lower on UE function than did the girls themselves. Differences in sex and parent responses based on the PODCI and patient Gross Motor Function Classification System levels have also been shown.20 However, Barnes et al3 reported that sex of a patient was not a significant predictor of the parent PODCI for children with CP.

r on UE function than did the girls themselves. Differences in sex and parent responses based on the PODCI and patient Gross Motor Function Classification System levels have also been shown.20 However, Barnes et al3 reported that sex of a patient was not a significant predictor of the parent PODCI for children with CP. If PODCI scores are collected on all children with a selected condition having musculoskeletal impact, regardless of treatment, meaningful comparisons between treatment and no-treatment groups can be made. A comparison group helps sort out the impact of coexisting factors, enabling a clear focus on the target condition. For example, in an article on children with CP,32 preoperative and postoperative PODCI scale scores were compared, showing increases in some scale scores. Without knowing what would be expected for changes with age, sex, or comorbidity, it is not possible to report that the multilevel surgery made the difference or whether the changes were due to maturation or changes in the comorbidity level. Using not only a population-based comparative database but also collecting data on age, sex, and comorbidity factors on children without surgical treatment as a comparative group would then allow more appropriate assessment of the impact of treatment.

changes were due to maturation or changes in the comorbidity level. Using not only a population-based comparative database but also collecting data on age, sex, and comorbidity factors on children without surgical treatment as a comparative group would then allow more appropriate assessment of the impact of treatment. AAOS and Pediatric Orthopaedic Society of North America recognized the value in developing an instrument that can be used to compare effects across different health conditions or diseases.33 It is beneficial to have not only disease-specific outcomes instruments, but also more generic instruments to allow comparisons across disorders and interventions.34 Either functional decline in certain diagnostic groups or a lack of typical development can be assessed by having population-based data available on a large group of children. Having specific details of age, sex, and comorbidities to compare across conditions is a critical piece of outcomes assessment in the era of the International Classification of Function, Disability, and Health and the holistic evaluation of the child. Supplementary Material SUPPLEMENTARY MATERIAL ACKNOWLEDGMENT The authors thank Erin Kelly, PhD, for her editorial support. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.pedorthopaedics.com. The authors declare no conflicts of interest.

Adolescent idiopathic scoliosis (AIS) is an abnormal curvature of the spine, which develops during puberty, and is the most prevalent musculoskeletal deformity affecting children.1 Global rates of AIS range from 0.9% to 12% and within this population approximately 10% of adolescents will eventually need some form of treatment.2 For the past 45 years, the most common nonsurgical treatment of AIS has been brace treatment. The objective of bracing is to stop curve progression and restore normal alignment of the spine by using active pressure from the brace. Recommended brace wear is typically at least 18 h/d with treatment lasting from 2 to 4 years until the end of bone growth or until the curve progresses to 50 degrees, which is an indication for surgery.3 Recent evidence from the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) confirmed the effectiveness of brace treatment, including a strong dose-response relationship, in preventing spinal curve progression to the threshold for surgery.4,5

e curve progresses to 50 degrees, which is an indication for surgery.3 Recent evidence from the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) confirmed the effectiveness of brace treatment, including a strong dose-response relationship, in preventing spinal curve progression to the threshold for surgery.4,5 Although clinical evidence regarding bracing effectiveness continues to strengthen, there is still uncertainty regarding the impact of brace wear on psychosocial well-being, as well as the impact of psychological well-being on brace wear adherence. Some research has found that full-time brace wear can negatively impact a patient’s, emotional, and social well-being, including a significant worsening of body image.6 In addition, research has found that the adverse effects on a patients’ psychosocial well-being induced by brace treatment can then result in poor brace wear adherence.7–9 Furthermore, some research indicates that interventions aimed at improving poor psychological outcomes can improve brace adherence.9,10 However, other research has found no negative impact on psychological well-being induced by brace treatment.11–15

ed by brace treatment can then result in poor brace wear adherence.7–9 Furthermore, some research indicates that interventions aimed at improving poor psychological outcomes can improve brace adherence.9,10 However, other research has found no negative impact on psychological well-being induced by brace treatment.11–15 Some of the discrepancies in the brace wear adherence research could be due to the type of brace wear data used to assess adherence. The majority of research on brace wear adherence is based on subjective reports, such as self-reports through brace wear diaries and logs. In these studies adherence rates have ranged from 41% of wearing hours/prescribed to as high 100% of wearing hours prescribed.16,17 According to Hunter et al, using subjective reports of brace wear adherence has been a major barrier for research assessing relationships between brace wear adherence and clinical and/or psychosocial outcomes.17 This study addressed this limitation, by using monitor data from BrAIST rather than self-reports to assess relationships among body image, quality of life (QOL), and brace wear adherence. The secondary aims of BrAIST were to assess whether there are any substantial psychosocial effects induced by brace treatment. This study used data from BrAIST, including subject questionnaires, brace monitor data, and clinical data regarding physical deformity. The purpose of this study was to assess relationships, including changes over time, among body image, QOL, major curve, and brace wear adherence in female adolescents with AIS.

atment. This study used data from BrAIST, including subject questionnaires, brace monitor data, and clinical data regarding physical deformity. The purpose of this study was to assess relationships, including changes over time, among body image, QOL, major curve, and brace wear adherence in female adolescents with AIS. METHODS BrAIST was a multicenter trial (22 sites in the United States and 3 sites in Canada) that either randomized (randomized arm) adolescents into 2 treatment groups (brace or observation) or allowed the adolescent to choose (preference arm) brace treatment or observation. Adolescents in BrAIST were considered to be at highest risk for major curve progression due to their age, skeletal immaturity, and degree of the major curve. Adolescents in the study had major curves between 20 and 40 degrees at baseline and had no previous orthopaedic treatment (brace or surgery) for treatment of AIS. Adolescents were instructed to wear a thoracolumbosacral orthosis, such as a Boston, Wilmington, or one of several other thoracolumbosacral orthosis brace designs, for at least 18 h/d and were asked to wear a monitor in their brace to track brace wear adherence. BrAIST found brace wear with a mean of <6 h/d was associated with a 41% success rate (skeletal maturity without curve progression <50 degrees or more), which was similar to the success rate of 48% in the observation group.4 Brace wear averaging at least 12.9 h/d was associated with success rates of 90% to 93%.4 On the basis of these findings, this study categorized patients as “least-adherent” (0 to 6 h/d) or “most-adherent” (>12 h/d). Baseline brace wear was determined from monitor data within the first 2 months of brace wear.

on group.4 Brace wear averaging at least 12.9 h/d was associated with success rates of 90% to 93%.4 On the basis of these findings, this study categorized patients as “least-adherent” (0 to 6 h/d) or “most-adherent” (>12 h/d). Baseline brace wear was determined from monitor data within the first 2 months of brace wear. Owing to the small number of males in this population, only females were included in this study. Adolescents could switch treatment, to observation or to brace, at any point during the study. Female adolescents (n=37) that switched from observation to brace treatment were also included in the study. For female adolescents that switched to brace treatment, the visit that they started brace treatment became their baseline visit. The Scoliosis Research Society defines brace treatment failure as an increase in curve magnitude of at least ≥6.18 Therefore, this study also assessed whether body image and QOL were impacted by changes in the major curve over time by grouping adolescents that had an increase that was ≥6 degrees in the major curve at the 12-month follow-up visit and those that did not.

ent failure as an increase in curve magnitude of at least ≥6.18 Therefore, this study also assessed whether body image and QOL were impacted by changes in the major curve over time by grouping adolescents that had an increase that was ≥6 degrees in the major curve at the 12-month follow-up visit and those that did not. The SAQ scores include the following 3 body image domains: appearance, expectations, and total score. The appearance domain (items 1 to 7, and 9) measures how the adolescent thinks she currently looks by using pictures of body areas oftentimes effected by AIS that include varying levels of deformity. Each picture is ranked on a 5-point scale with varying levels of deformity with 5 being the most deformed. The appearance domain scores range from 8 to 40. The SAQ expectation domain (items 10 to 17) is also ranked on a 5-point scale with 5 indicating a strong desire to look more “normal” regarding some aspect of their appearance such as wanting more even hips or shoulders. The expectation domain scores range from 8 to 40. The SAQ total score is the sum of the appearance domain and the expectation domain (range, 16 to 80). Higher SAQ total scores indicate a larger discrepancy between how individuals’ think they currently look (appearance domain) and how they want to look (expectation domain), which is an indication of overall poor body image. Previous research indicates that the SAQ is a valid measure of body image.19,20

ange, 16 to 80). Higher SAQ total scores indicate a larger discrepancy between how individuals’ think they currently look (appearance domain) and how they want to look (expectation domain), which is an indication of overall poor body image. Previous research indicates that the SAQ is a valid measure of body image.19,20 Patients also completed the PedsQL 4.0 Generic Corse Scales at each visit. The PedsQL has been shown to distinguish health-related QOL between healthy children and children with chronic illnesses.21,22 Scores on the PedsQL range from 0 to 100 with higher scores indicating better QOL. The questionnaire consists of 23 items applicable to healthy populations, as well as populations with acute and chronic health conditions. The QOL measures include the following psychosocial domains: health and activities, feelings, how well one gets along with others, and school. The SAQ and QOL scores were not normally distributed therefore the Wilcoxon rank-sum test was used for comparison between the 2 brace wear adherent groups. Spearman rank correlation was conducted to explore correlations within each adherent group. Finally, for comparison of variable change over time within groups, paired t tests were conducted. All significance tests were 2-tailed and conducted at the 5% significance level.

arison between the 2 brace wear adherent groups. Spearman rank correlation was conducted to explore correlations within each adherent group. Finally, for comparison of variable change over time within groups, paired t tests were conducted. All significance tests were 2-tailed and conducted at the 5% significance level. RESULTS In the study population (n=167), the mode of the appearance score was 2, which was the second least distorted picture of the 5 images of physical distortion and the mode for the expectation score was 2, which was a “somewhat true” response to wanting to look more normal regarding certain aspects of the body. The following were the median scores of each SAQ body image domain: appearance was 17, expectation was 16, and total score was 34. The mean QOL score at baseline was 84.6 (±13.7), which is similar to the healthy adolescent population.22 At baseline, 126 (75%) of female patients were in the least-adherent group (n=39) or the most-adherent (n=92) brace wear groups. In general, the curve patterns or location of the curvature did not have an effect on brace adherence. There were no significant differences between the least-adherent and the most-adherent groups with regard to age, body mass index, QOL scores, and SAQ’s appearance, expectation, and total scores. Table 1 describes the baseline demographic, clinical, SAQ body image domains, and QOL by least-adherent and most-adherent brace wear groups. TABLE 1 Brace Baseline Characteristics for Least-adherent and Most-adherent Brace Wear

At baseline, 126 (75%) of female patients were in the least-adherent group (n=39) or the most-adherent (n=92) brace wear groups. In general, the curve patterns or location of the curvature did not have an effect on brace adherence. There were no significant differences between the least-adherent and the most-adherent groups with regard to age, body mass index, QOL scores, and SAQ’s appearance, expectation, and total scores. Table 1 describes the baseline demographic, clinical, SAQ body image domains, and QOL by least-adherent and most-adherent brace wear groups. TABLE 1 Brace Baseline Characteristics for Least-adherent and Most-adherent Brace Wear Table 2 summarizes the relationships between body image scores and QOL in the least-adherent and most-adherent groups at baseline, 6, 12, and 18 months. TABLE 2 Spearman Rank Correlations in SAQ Scores With Adherence and QOL Over Time In general, there were no significant correlations between SAQ body image domains and QOL in the least-adherent group. In the most-adherent group, all 3 body image domains had significant negative correlations with QOL at baseline, 6 months, and 12 months, which indicates poorer body image is significantly correlated with poorer QOL. However, there were no longer significant correlations between body image domains and QOL at the 18-month visit. Table 3 summarizes the SAQ body image domains, QOL, and brace wear adherence between groups and within groups for patients who did or did not have a ≥6 degree increase in major curve during the first 12 months of brace treatment.

In general, there were no significant correlations between SAQ body image domains and QOL in the least-adherent group. In the most-adherent group, all 3 body image domains had significant negative correlations with QOL at baseline, 6 months, and 12 months, which indicates poorer body image is significantly correlated with poorer QOL. However, there were no longer significant correlations between body image domains and QOL at the 18-month visit. Table 3 summarizes the SAQ body image domains, QOL, and brace wear adherence between groups and within groups for patients who did or did not have a ≥6 degree increase in major curve during the first 12 months of brace treatment. TABLE 3 Comparisons Between and Within Female Adolescents Having (Progression) and Not Having a ≥6 Degree Increase (No Progression) in Major Curve at the Brace Baseline and 12-month Visits There were no significant differences at baseline or at the 12-month visit in SAQ body image scores and QOL scores between adolescents that had a ≥6 degree increase in major curve compared with those that did not. In addition, there were no changes within each progression change group in body image scores or in QOL scores between the brace baseline and 12-month visit.

or at the 12-month visit in SAQ body image scores and QOL scores between adolescents that had a ≥6 degree increase in major curve compared with those that did not. In addition, there were no changes within each progression change group in body image scores or in QOL scores between the brace baseline and 12-month visit. DISCUSSION Previous research regarding the impact of brace wear adherence on psychosocial well-being and the impact of psychosocial well-being on brace wear adherence was conflicting. This study addressed several weakness of previous AIS research by using data from BrAIST. BrAIST was an innovative study because it combined components never included in previous AIS research including: being a multicenter trial, having a randomized control group, an a priori determination of effect size, use of blinded clinical outcome measurements, and use of objective brace wear monitor data to measure brace wear adherence.5 The purpose of this study was to assess whether there were any substantial negative psychosocial effects induced by brace treatment or whether poor psychosocial well-being negatively impacted brace wear adherence. This study analyzed relationships among brace wear adherence, body image, and QOL. When looking at differences between the least-adherent and the most-adherent brace wear groups, findings from this study supply no evidence that the amount of brace wear negatively impacts body image or QOL, or that poor body image and poor QOL negatively impacts brace wear adherence.

ar adherence, body image, and QOL. When looking at differences between the least-adherent and the most-adherent brace wear groups, findings from this study supply no evidence that the amount of brace wear negatively impacts body image or QOL, or that poor body image and poor QOL negatively impacts brace wear adherence. Results from this study do not support research suggesting that brace wear has a negative impact on body image and QOL, but corroborates previous studies which found brace treatment did not negatively impact psychosocial well-being.11–14 Results from this study are similar to previous BrAIST findings comparing females with AIS that were untreated (observation) to brace-treated females, which found that brace-treated females did not have significantly poorer body image or QOL compared with females undergoing observation.11

psychosocial well-being.11–14 Results from this study are similar to previous BrAIST findings comparing females with AIS that were untreated (observation) to brace-treated females, which found that brace-treated females did not have significantly poorer body image or QOL compared with females undergoing observation.11 Although there were no differences in body image and QOL between least-adherent and most-adherent groups, findings from this study suggest that for female adolescents that already have poor body image and poor QOL, wearing a brace for >12 hours may add another layer of distress to psychological well-being. However, the lack of significant correlations between body image and QOL at 18 months in the most-adherent treatment group suggests that adolescents may develop coping skills and adjust to the brace over time. These findings support several research studies indicating that, over time, adolescents undergoing brace treatment may develop self-protective, coping strategies that enables them to adapt to their new body image, and reestablish their social lives.9,11,13 Finally, results from this study indicate that, regardless of the amount of brace wear and whether adolescents had a significant worsening (≥6 degrees) of their major curve over time, body image and QOL were not significantly impacted in the first 12 months of brace treatment.

and reestablish their social lives.9,11,13 Finally, results from this study indicate that, regardless of the amount of brace wear and whether adolescents had a significant worsening (≥6 degrees) of their major curve over time, body image and QOL were not significantly impacted in the first 12 months of brace treatment. A limitation of this study might be the relatively small number of females in some of the adherence and degree of major curve progression groups over time and therefore the comparisons and correlations lack statistical power. Furthermore, although several studies have found the SAQ to be a valid and reliable measure for measuring body image19,20 other studies have found that adolescents had difficulty reading and comprehending the SAQ.23

urve progression groups over time and therefore the comparisons and correlations lack statistical power. Furthermore, although several studies have found the SAQ to be a valid and reliable measure for measuring body image19,20 other studies have found that adolescents had difficulty reading and comprehending the SAQ.23 Results from this study, in particular that the amount of time the brace was worn did not adversely impact body image and QOL, should be relayed to clinicians, adolescents, and parents so they can weigh the psychosocial risks and the lack of psychosocial risks with the clinical benefits of brace treatment. In addition, findings from this study indicate that adolescent’s body image and QOL should be assessed throughout brace treatment. When body image distress and/or poor QOL are detected, efforts should be made to improve both. If efforts to improve body image and QOL are not successful, the physician, adolescent, and parents should weigh the psychosocial risks with the clinical benefits of brace treatment and determine whether brace treatment and the amount of current prescribed brace wear is appropriate. For example, the benefit of reducing brace wear to <13 h/d might be more beneficial psychologically and socially than the clinical benefits of wearing the brace for >13 h/d.

ith the clinical benefits of brace treatment and determine whether brace treatment and the amount of current prescribed brace wear is appropriate. For example, the benefit of reducing brace wear to <13 h/d might be more beneficial psychologically and socially than the clinical benefits of wearing the brace for >13 h/d. The devices(s)/drugs(s) that is/are the subject of this manuscript is/are exempt from FDA or corresponding national regulations. The project described was supported by Award Numbers R21AR049587 and R01AR052113 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (S.L.W., PI); the Shriners Hospitals for Children (#79125, M.B. Dobbs, PI); the Canadian Institutes of Health Research (FRN-81050, J.G. Wright, PI); the University of Rochester (J.O. Sanders, PI); the Children’s Mercy Hospital and Clinics (N.J. Price, PI); and the Children’s Miracle Network (S.L.W., PI). For the remaining authors none were declared. The authors declare no conflicts of interest.

Osteogenesis imperfecta (OI) is a genetically determined disorder of connective tissue characterized by bone fragility, deformities of long bones, and short stature.1,2 Ekman provided the first scientific description of OI in 1788, but it was not until 1849 that Vrolik coined the term to describe the condition.3 OI affects up to 1/10,000 individuals of all racial and ethnic origins.4,5 OI is characterized by decreased bone quality and quantity and variable bone deformities secondary to either decreased or abnormally produced collagen. The majority of patients have a mutation in either the COL1A1 or the COL1A2 gene,6,7 the 2 genes coding for the α-1 and α-2 chains of collagen type I, respectively.8 Collagen type I is a heterotrimer consisting of 2 α-1 chains and 1 α-2 chain. It is initially synthesized as a pro-α chain with a propeptide at each end (N-propeptide and C-propeptide). The C-propeptide is necessary for pro-α chain association and triple helix formation, which starts at the C-terminal propeptide and extends to the N-terminal propeptide in a zipper-like manner.8 The prevalence of hip dysplasia in the general population is 0.7 to 1.2 per 1000 births.9 The predisposing risk factors for hip dysplasia are a positive family history, perinatal breech positioning, and ligamentous laxity.10 An association has also been reported between hip dysplasia and disorders associated with ligamentous laxity, such as Down syndrome, Ehlers-Danlos syndrome, Larsen syndrome, and Marfan syndrome.11–13

ng risk factors for hip dysplasia are a positive family history, perinatal breech positioning, and ligamentous laxity.10 An association has also been reported between hip dysplasia and disorders associated with ligamentous laxity, such as Down syndrome, Ehlers-Danlos syndrome, Larsen syndrome, and Marfan syndrome.11–13 Screening of infants for hip dysplasia prevents late presentation of this disorder with irreversible complications. Screening is done clinically by performing Ortolani and Barlow tests and by use of ultrasonography.10,14 The clinical screening for hip dysplasia in infants with OI often is not easy, however, because of femoral bone deformity and the risk of fractures in these patients. Reported femur fractures have occurred in children with OI after clinical testing for hip dysplasia.15 Although there is a case report that described the association of hip dysplasia with OI in 1969,16 no other reports or case series described the association with collagen type I C-propeptide mutation. On the basis of this, we performed the present retrospective case series study to gather information on how best to screen for, diagnose, and treat hip dysplasia in patients with OI.

Screening of infants for hip dysplasia prevents late presentation of this disorder with irreversible complications. Screening is done clinically by performing Ortolani and Barlow tests and by use of ultrasonography.10,14 The clinical screening for hip dysplasia in infants with OI often is not easy, however, because of femoral bone deformity and the risk of fractures in these patients. Reported femur fractures have occurred in children with OI after clinical testing for hip dysplasia.15 Although there is a case report that described the association of hip dysplasia with OI in 1969,16 no other reports or case series described the association with collagen type I C-propeptide mutation. On the basis of this, we performed the present retrospective case series study to gather information on how best to screen for, diagnose, and treat hip dysplasia in patients with OI. METHODS After receiving institutional review board approval, we retrospectively reviewed the charts of all patients with a diagnosis of OI who were seen at Shriners Hospital for Children-Canada between 1999 and 2013 to identify patients who had a diagnosis of hip dysplasia. We extracted the clinical characteristics of patients with hip dysplasia from their charts. This included information about the genetic mutation that caused OI in these children. In addition, the screening, treatment, complications, duration of follow-up, and clinical outcomes of treating these dysplastic hips were reviewed. Moreover, radiographic evaluation of all patients was done, including the assessment of acetabular indices and assessment of the concentric reduction and the development of ossified femoral nucleus to exclude any vascular compromise to the femoral head (Table 1).

utcomes of treating these dysplastic hips were reviewed. Moreover, radiographic evaluation of all patients was done, including the assessment of acetabular indices and assessment of the concentric reduction and the development of ossified femoral nucleus to exclude any vascular compromise to the femoral head (Table 1). TABLE 1 Patient Demographics and Results Statistical Analysis The results were reported with the use of descriptive statistics. Testing for statistical significance was not performed due to the small number of cases in this series. RESULTS A total of 687 children with a diagnosis of OI were assessed at our center during the observation interval. Among these, 5 patients (4 boys, 1 girl) were diagnosed with hip dysplasia, affecting a total of 8 hips. Review of the genetic information revealed that in 4 of these 5 children (80%), OI was caused by mutations affecting the C-propeptide of the collagen type I α-1 chain, no one of these patients is related to the others, whereas in the entire group of children with OI, C-propeptide mutations were present in a total of 26 patients. Thus, the prevalence of hip dysplasia was 0.87% (5 of 687) in the entire study cohort, but 15% (4 of 26) among patients with C-propeptide mutations.

1 chain, no one of these patients is related to the others, whereas in the entire group of children with OI, C-propeptide mutations were present in a total of 26 patients. Thus, the prevalence of hip dysplasia was 0.87% (5 of 687) in the entire study cohort, but 15% (4 of 26) among patients with C-propeptide mutations. The diagnosis of hip dysplasia had been made between 3 weeks and 27 months of age (mean: 13.9 mo). Early clinical screening failed to diagnose hip dysplasia in all cases except 1. Pavlik harness treatment was used in 2 children but failed. All patients underwent surgical treatment, including either a closed or an open reduction and a femoral osteotomy. Four hips had closed reduction with a femoral osteotomy. Open reduction with a femoral osteotomy was performed in 4 hips and pelvic osteotomy was performed in 2 hips. There was 1 case of redislocation after an open reduction and 1 case of osteonecrosis of the femoral head after treatment with a Pavlik harness. The range of follow-up duration was 8 months to 9 years with an average of 3.4 years.

a femoral osteotomy was performed in 4 hips and pelvic osteotomy was performed in 2 hips. There was 1 case of redislocation after an open reduction and 1 case of osteonecrosis of the femoral head after treatment with a Pavlik harness. The range of follow-up duration was 8 months to 9 years with an average of 3.4 years. Case 1 This boy presented to the OI team at the age of 7 months. He was born by spontaneous vaginal delivery in a breech presentation following an uneventful pregnancy. His mother did not notice any intrauterine movements at all during her pregnancy. There was no family history of OI or hip dysplasia. At birth, asymmetric movements of the lower limbs were noted. He was diagnosed with OI at another institution. At 3 weeks of age, bilateral hip dysplasia was diagnosed at that institution and the patient was treated with a Pavlik harness. When the harness was put on, fractures of both femurs, the proximal left tibia, and the proximal right fibula were noted. The decision at that time was to do nothing about the hip dysplasia until the femur fractures had healed, to keep the Pavlik harness, and to start bisphosphonate infusion. Closed reduction and hip spica cast application were not chosen because these can lead to further osteopenia. The plan was rather to perform an open reduction at the same time as femoral osteotomy and rodding. Although we recommended removal of the Pavlik harness, it was continued by the other institution. The patient was seen again in our institution at the age of 13 months with a failed Pavlik harness treatment. The x-ray showed bilateral hip dysplasia and signs of type I bilateral avascular necrosis according to Kalamchi and McEwen’s17 classification, which was confirmed by magnetic resonance imaging. When he started walking at the age of 23 months, the patient underwent left hip open reduction, femoral shortening osteotomy, and telescoping rodding and a hip spica was applied for 6 weeks. The concentricity of reduction was confirmed by a computed tomography scan. One year later, closed reduction femoral osteotomy and telescoping rodding were performed on the right side. The x-ray of both hips showed that both hips are reduced and well developed (Fig. 1).

rodding and a hip spica was applied for 6 weeks. The concentricity of reduction was confirmed by a computed tomography scan. One year later, closed reduction femoral osteotomy and telescoping rodding were performed on the right side. The x-ray of both hips showed that both hips are reduced and well developed (Fig. 1). FIGURE 1 A, X-ray of both hips at 18 months of age showing a bilateral hip dislocation. B, Final x-ray showing healed osteotomy sites with concentrically reduced hips with no signs of avascular necrosis. Case 2 This girl was born at term, and diagnosed with OI after birth because of multiple fractures. Bilateral hip dysplasia was diagnosed at 8 months of age. Because of ligamentous laxity and ability to reduce the hip initial treatment started with a Pavlik harness application for 3 months, which failed to keep both hips reduced. At the age of 3 years, open reduction of the left hip, Salter osteotomy, femoral varus derotational osteotomy, and telescopic rodding of the left femur were performed. At the age of 6 years, closed reduction of the right hip, femoral varus derotational osteotomy, telescopic rodding of the right femur, and a Dega osteotomy of the right hip were performed. The treatment of the right hip was delayed as the patient came from another country. At the age of 7 years, the patient was able to walk without any aid, and both hips were reduced and stable clinically and radiologically.

omy, telescopic rodding of the right femur, and a Dega osteotomy of the right hip were performed. The treatment of the right hip was delayed as the patient came from another country. At the age of 7 years, the patient was able to walk without any aid, and both hips were reduced and stable clinically and radiologically. Case 3 OI was diagnosed at birth for this boy. Right hip dysplasia was diagnosed at the age of 10 months. Treatment of the right hip was done at the age of 19 months by an open reduction, femoral osteotomies, and insertion of telescopic rods in both femurs. At the age of 23 months, the patient started to stand, and his right hip appeared dislocated on the x-ray. A night abduction brace was applied until his scheduled revision surgery. Case 4 A clinical diagnosis of OI at birth of this boy was made and genetic testing revealed a glycine mutation in the triple helical part of the COL1A2 gene (Table 1). Thus, this is the only patient in the present series who does not have a C-propeptide mutation. Right hip dysplasia was diagnosed at the age of 24 months and was treated initially by closed reduction, left femoral osteotomies, and a telescoping rodding. The right hip failed to reduce. Three weeks later, the patient underwent open reduction of the right hip, femoral osteotomies, and insertion of a telescoping rod in the right femur. X-rays of both hips showed that the right femoral head is still located in the acetabulum.

femoral osteotomies, and a telescoping rodding. The right hip failed to reduce. Three weeks later, the patient underwent open reduction of the right hip, femoral osteotomies, and insertion of a telescoping rod in the right femur. X-rays of both hips showed that the right femoral head is still located in the acetabulum. Case 5 OI was diagnosed after this boy was born at term because of multiple fractures. Dysplasia of both hips was noted at the age of 27 months and was treated by closed reduction, varus femoral osteotomy, and telescoping rods. Three months after surgery, the patient started walking and radiographs of both hips showed that both femoral heads were located in the acetabulum, with no evidence of avascular necrosis.

a of both hips was noted at the age of 27 months and was treated by closed reduction, varus femoral osteotomy, and telescoping rods. Three months after surgery, the patient started walking and radiographs of both hips showed that both femoral heads were located in the acetabulum, with no evidence of avascular necrosis. DISCUSSION In this study, we found that 5 out of 687 children with OI had hip dysplasia. There is no known cause for hip dysplasia, although there are associated risk factors such as female sex, first born, breech presentation, and ligamentous laxity. A C-propeptide mutation was present in 26 of the 687 children with OI. Four of the 5 children diagnosed with hip dysplasia concomitant with OI (80%) had a confirmed C-propeptide mutation. The mechanistic link between C-propeptide mutations and hip dysplasia is not clear at present. However, these results show that patients with C-propeptide mutations need to be carefully assessed for hip dysplasia, particularly if the newborn is delivered in a breech presentation and/or the presence of a femur recurvatum (Fig. 2). To our knowledge, no case series have previously been published describing the association of hip dysplasia with OI in children. However, 2 cases in siblings have been reported.16 The prevalence of hip dysplasia in our series of patients is therefore 7 per 1000, which is higher than the prevalence in the general population (0.7 to 1.2 per 1000 live births).9,18,19 Sponseller et al13 reported an incidence of hip dysplasia of 2% in association with Marfan syndrome. Our case series included 4 boys (80%) and only 1 girl (20%), which is in contrast with the female predominance for hip dysplasia (81% female predominance) in the general population.20

o 1.2 per 1000 live births).9,18,19 Sponseller et al13 reported an incidence of hip dysplasia of 2% in association with Marfan syndrome. Our case series included 4 boys (80%) and only 1 girl (20%), which is in contrast with the female predominance for hip dysplasia (81% female predominance) in the general population.20 FIGURE 2 Anteroposterior view of both hips and femurs at 24 months of age; on the left side the typical procurvatum deformity of the femur, and on the right side the recurvatum due to the breech presentation.

o 1.2 per 1000 live births).9,18,19 Sponseller et al13 reported an incidence of hip dysplasia of 2% in association with Marfan syndrome. Our case series included 4 boys (80%) and only 1 girl (20%), which is in contrast with the female predominance for hip dysplasia (81% female predominance) in the general population.20 FIGURE 2 Anteroposterior view of both hips and femurs at 24 months of age; on the left side the typical procurvatum deformity of the femur, and on the right side the recurvatum due to the breech presentation. Hip dysplasia was diagnosed late in 4 children because of the rarity of this association and fear of causing a fracture during clinical examination, as reported in a case series in which fractures of the femur occurred during testing for hip dysplasia.15 Clinical examination was difficult in these children because of the deformed femur; hyperlaxity, which results in full abduction with clinical examination; and the presence of other conditions such as club feet, which was treated in 1 child by the Ponseti method before the hip dysplasia was diagnosed. Treatment with a Pavlik harness was attempted in 2 patients but was not effective in either case. One case in which the harness was applied for 6 months had osteonecrosis of the femoral head, which was confirmed by magnetic resonance imaging. Because of the rarity of the condition, we could not find ultrasound classification in the charts, and we were not able to classify the starting severity and if any improvement was noted, however, this is an area for further research. The unsuccessful results of the harness may be related to the ligamentous laxity or the femoral bone deformity, late application, and the presence of fractures. The reported failure rate of treatment of frank hip dislocation in children with a Pavlik harness is 25%.21 Closed reduction was reported to be successful for treating hip dysplasia in a series of 4 children with hip dysplasia associated with Marfan syndrome.13 The surgical treatment of hip dysplasia in children older than 18 months is redirectional femoral osteotomies and acetabular osteotomies, but in younger children the surgical treatment is adductor tenotomy and closed reduction versus open reduction often without osteotomies.22 In our series, we think that the associated femoral deformity and fractures in the OI patients made the concentric reduction more difficult and a femoral varus derotational shortening osteotomy was the key to maintaining a concentric reduction and not a pelvic osteotomy. We had to use concomitant pelvic osteotomies in 2 hips (1 patient) only because of the significant acetabular dysplasia.

res in the OI patients made the concentric reduction more difficult and a femoral varus derotational shortening osteotomy was the key to maintaining a concentric reduction and not a pelvic osteotomy. We had to use concomitant pelvic osteotomies in 2 hips (1 patient) only because of the significant acetabular dysplasia. All acetabular indices have gone back to normal except for the third case (29 degrees). He is on an abduction brace and scheduled for revision of open reduction of the dislocated hip. CONCLUSIONS About 80% of OI patients with hip dysplasia are associated with C-propeptide mutation. Clinical screening for hip dysplasia is difficult in OI patients owing to bowing of the proximal femur and the risk of causing fractures. Therefore, all OI children with positive C-propeptide mutation should be screened for hip dysplasia with ultrasound. We did not find any role for the Pavlik harness in treating hip dysplasia in OI children. Management was achieved by a femoral osteotomy with either closed or open reduction of the hips with or without concomitant pelvic osteotomy. None of the authors received financial support for this study. M.G. is a consultant for smith and nephew, and issued a patent from Pega medical. F.R. recieved grants from The Canadian Institutes of Health Research. The other authors declare no conflicts of interest.

Limb-length discrepancy (LLD) is a frequently encountered complaint in pediatric orthopaedic practice. Common causes include congenital conditions (fibular hemimelia and congenital femoral deficiency), hemihypertrophy, posttraumatic deformities, and posttumoral resection sequelae, among others. Accurate LLD prediction at maturity is of utmost importance, given that it will determine the timing and treatment method. The multiplier method (MM) is a simple and accurate method for discrepancy predictions.1–3 It is based on the data presented by Anderson et al4 and has been tested with 19 other databases of bone lengths, including anthropologic data of skeletal remains of children.5 It was calculated by dividing the bone length at maturity by the length at each age for each age percentile group. This gives a multiplier constant for each age. These multiplier constants are different for boys and girls but are independent of race, nationality, and generation.1 In 2011, a mobile platform software was developed [“Multiplier App” (MA)] for the Apple iOS and Google Android platforms that is able to calculate the LLD at maturity, timing for epiphysiodesis, foot length, height at maturity, and other clinically relevant values. This software uses the same formulae as the traditional “paper and pencil” MM.

rm software was developed [“Multiplier App” (MA)] for the Apple iOS and Google Android platforms that is able to calculate the LLD at maturity, timing for epiphysiodesis, foot length, height at maturity, and other clinically relevant values. This software uses the same formulae as the traditional “paper and pencil” MM. The current study seeks to compare MA with the traditional MM (calculations by hand). The mobile application eliminates the need for cumbersome formulae, paper charts, and calculations using pencil, paper, and a calculator. It may also reduce the amount of human error during calculations of complex formulae. We hypothesized that the mobile MA is more accurate and faster than the traditional MM done by hand with a calculator.

eliminates the need for cumbersome formulae, paper charts, and calculations using pencil, paper, and a calculator. It may also reduce the amount of human error during calculations of complex formulae. We hypothesized that the mobile MA is more accurate and faster than the traditional MM done by hand with a calculator. METHODS After receiving Institutional Review Board approval, 30 residents who were rotating through our service were asked to participate in this study. Eighteen residents were postgraduate year 1 (PGY-1), 6 were PGY-2, 4 were PGY-3, and 2 were PGY-4 with little or no previous knowledge of the MM. Initially, they attended an introductory training class that taught them about LLD and timing of epiphysiodesis using the MM and MA. In a second class, questions about clinical cases were given to the residents. They solved these questions using the MM and MA while receiving supervision and help from one of the authors. Finally, 2 timed tests were administered at 2-week intervals to the same group of residents who participated in the above-mentioned training classes. For 1 test, the residents solved the questions using the traditional paper and pencil MM. For the other test, the same questions were solved using the MA (Fig. 1). Each resident was randomized as to the method he or she applied first using a “coin flip” for randomization.

ipated in the above-mentioned training classes. For 1 test, the residents solved the questions using the traditional paper and pencil MM. For the other test, the same questions were solved using the MA (Fig. 1). Each resident was randomized as to the method he or she applied first using a “coin flip” for randomization. FIGURE 1 The study participants were given the following clinical problem about limb-length discrepancy (LLD). A 6-year-old girl with proximal focal femoral deficiency of the right femur has bone lengths of 15 cm (right femur) and 20.3 cm (left femur). What will be the difference at maturity? A, To solve this problem using the Multiplier App, the study participant would first select the “Lower Extremity” option from the main menu. B, From the “Lower Extremity” screen, the participant would then select “LLD (congenital)”. C, The “LLD (congenital)” screen allows the user to input data. The participant enters the limb segment (femur), sex (female), age (6 y), and LLD (20.3−15.0 cm=5.3 cm LLD). No information is provided about prior lengthening amounts in the question, so the participant leaves this field blank and then presses the calculate button. D, The results screen shows that the discrepancy will be 8.0 cm at maturity. To see the LLD at every age, the participant presses the “LLD (congenital) at every age” button. Reprinted with permission. Copyright 2015 [Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, Baltimore, MD]. All permission requests for this image should be made to the copyright holder.

m at maturity. To see the LLD at every age, the participant presses the “LLD (congenital) at every age” button. Reprinted with permission. Copyright 2015 [Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, Baltimore, MD]. All permission requests for this image should be made to the copyright holder. The test consisted of 5 clinical examples of hypothetical patients (refer to Supplemental Data File that shows LLD Exercises, Supplemental Digital Content 1, http://links.lww.com/BPO/A69). Residents were asked to calculate developmental and congenital LLD and timing of epiphysiodesis. The amount of time taken to complete the 5 questions was measured for each participant as a quantitative continuous variable. The accuracy of the answers was determined by using an answer key that was prepared by the senior author. The results were tabulated as “correct” or “incorrect” to obtain a quantitative discrete variable. When an incorrect answer was given, the source of the error was recorded. Lastly, after both tests were administered, the residents were asked to choose their preferred method in terms of ease of use and likelihood of using it in future practice. All tests were answered anonymously. Residents were excluded from the study if they did not answer all the questions, did not take both tests, or had previous experience with this topic.

red, the residents were asked to choose their preferred method in terms of ease of use and likelihood of using it in future practice. All tests were answered anonymously. Residents were excluded from the study if they did not answer all the questions, did not take both tests, or had previous experience with this topic. To obtain an adequate sample size, an estimated difference of 20% in accuracy and 100% in time between methods was calculated. To obtain a confidence level of 95% with a power of 80%, an estimated sample size of 30 subjects per group was required.

red, the residents were asked to choose their preferred method in terms of ease of use and likelihood of using it in future practice. All tests were answered anonymously. Residents were excluded from the study if they did not answer all the questions, did not take both tests, or had previous experience with this topic. To obtain an adequate sample size, an estimated difference of 20% in accuracy and 100% in time between methods was calculated. To obtain a confidence level of 95% with a power of 80%, an estimated sample size of 30 subjects per group was required. RESULTS Thirty residents each took the same test 2 times: once using the MM and once using the MA. The average amount of time required to complete the test using the traditional MM and the MA was 22 (range, 15 to 45) minutes and 8 (range, 4 to 15) minutes, respectively (P<0.001). Regarding the accuracy, an average of 3 (60%) of 5 questions (range, 20% to 100%) were answered correctly using the MM and 4 (80%) of 5 questions (range, 40% to 100%) using the MA (P=0.001). The most common errors for the MM were arithmetic errors (23 errors), incorrect choice of the appropriate formula (10 errors), selecting the wrong limb segment for the location of epiphysiodesis (8 errors), and using the current discrepancy instead of the discrepancy at maturity for the timing of epiphysiodesis calculations (7 errors). The most common errors observed for the MA were using the current discrepancy instead of the discrepancy at maturity for the timing of epiphysiodesis calculations (9 errors), inputting the patient’s sex incorrectly (8 errors), and selecting the wrong limb segment for the location of the epiphysiodesis (7 errors). No difference in accuracy or time taken to answer the questions for the 2 test groups was observed (P>0.05) when the results were separated on the basis of whether participants took the first test using the MA or MM. All residents stated that they would prefer to use the MA in the future instead of the MM.

(7 errors). No difference in accuracy or time taken to answer the questions for the 2 test groups was observed (P>0.05) when the results were separated on the basis of whether participants took the first test using the MA or MM. All residents stated that they would prefer to use the MA in the future instead of the MM. DISCUSSION In pediatric orthopaedic practices, LLD is a frequent clinical challenge. Parents need to know what the predicted discrepancy will be at skeletal maturity, and when, if advisable, epiphysiodesis should be performed. There are 4 main methods used for discrepancy prediction: the arithmetic method; the growth-remaining method4,6; the straight-line graph method7; and the MM.1 Anderson et al4 presented longitudinal data in 1963 that included the lengths of femora and tibiae in boys and girls according to chronological age from 1 year to the age at skeletal maturity. All current methods that predict LLD are based on these data. The Moseley method7 converts the data from the study by Anderson et al4 into a straight line by modifying the age scale. This method requires at least 2 or 3 data points obtained at least 1 year apart to accurately predict the LLD.

age at skeletal maturity. All current methods that predict LLD are based on these data. The Moseley method7 converts the data from the study by Anderson et al4 into a straight line by modifying the age scale. This method requires at least 2 or 3 data points obtained at least 1 year apart to accurately predict the LLD. Several reports state that the traditional MM is quick, accurate, and easy to use in comparison with other methods1,2,8–11 for calculating limb discrepancies in prenatal patients, upper-limb and lower-limb discrepancies, and timing of epiphysiodesis. It has been shown that a more accurate discrepancy prediction can be obtained when bone age is used instead of chronological age in the MM.12 Recently, a study that compared the remaining growth, straight line, and MMs showed that the Green-Anderson growth remaining method was the most accurate approach for predicting the timing of epiphysiodesis.13

ccurate discrepancy prediction can be obtained when bone age is used instead of chronological age in the MM.12 Recently, a study that compared the remaining growth, straight line, and MMs showed that the Green-Anderson growth remaining method was the most accurate approach for predicting the timing of epiphysiodesis.13 Our results demonstrate a clear advantage for the MA in the time needed to answer the 5 clinical questions (almost 3 times faster) and in its accuracy (20% more accurate). In clinical practice, performing the calculations can be cumbersome and time-consuming. Some attempts have been made to simplify these calculations. Sanders et al14 published an Excel spreadsheet (Microsoft Inc., Redmond, WA) to help with the MM calculations. The most common mistakes observed using the MM were mathematical errors followed by incorrect application of formulae. This is one of the greatest advantages of the MA: it helps prevent arithmetic errors and the specific formulae do not have to be selected by the clinician.

edmond, WA) to help with the MM calculations. The most common mistakes observed using the MM were mathematical errors followed by incorrect application of formulae. This is one of the greatest advantages of the MA: it helps prevent arithmetic errors and the specific formulae do not have to be selected by the clinician. The MA was developed in an attempt to further simplify and streamline these calculations for a mobile platform. It is available for free under the name “Multiplier” for both the Apple iOS and Google Android platforms. Since the launch of the app in 2011, several updates have been released to make it easier to use and more attractive. Also, more detailed explanations and additional functionality have been added as well as improvements in the interface to prevent human errors when inputting data and choosing the correct formula. When the test was administered for this research, a default sex (male) was preselected in the MA data entry screens. Inputting the patient’s sex incorrectly was the second most common mistake with the MA. On the basis of these results, the developers (S.C.S., J.E.H.) modified the MA so that no default sex was preselected and an alert message was generated if the user did not indicate the patient’s sex.

d in the MA data entry screens. Inputting the patient’s sex incorrectly was the second most common mistake with the MA. On the basis of these results, the developers (S.C.S., J.E.H.) modified the MA so that no default sex was preselected and an alert message was generated if the user did not indicate the patient’s sex. The strengths of our study include that it is a well-designed, prospective, randomized trial, with an adequate power to answer the hypotheses. A potential weakness is that residents are familiar with smartphones and their applications, but they may not be as adept at performing mathematic calculations. In summary, the free MA is simpler and more accurate in practice than the traditional pencil and paper MM. No method is foolproof, as the clinician still has to have a thorough understanding of the subject matter to use either method. Supplementary Material Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.pedorthopaedics.com. None of the authors received financial support for this study.

The strengths of our study include that it is a well-designed, prospective, randomized trial, with an adequate power to answer the hypotheses. A potential weakness is that residents are familiar with smartphones and their applications, but they may not be as adept at performing mathematic calculations. In summary, the free MA is simpler and more accurate in practice than the traditional pencil and paper MM. No method is foolproof, as the clinician still has to have a thorough understanding of the subject matter to use either method. Supplementary Material Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.pedorthopaedics.com. None of the authors received financial support for this study. S.C.S. is a paid consultant for Ellipse Technologies, receives stock options from Ellipse Technologies, and receives royalties from Pega Medical and Ellipse Technologies. J.E.H. is a paid consultant for OrthoPediatrics and receives research support from Ellipse Technologies. The institution of S.C.S. and J.E.H. received support from the following companies to support its nonprofit organization: Stryker, Orthocare Solutions, and Metro Prosthetics. The following companies supported an annual course for orthopaedic surgeons that is held by the institution of J.E.H. and S.C.S.: Smith & Nephew, Ellipse Technologies, Stryker, Brainlab, Depuy Synthes, Orthofix, Biomet, KCI, OrthoPediatrics, OHK Medical Devices, and The MHE Coalition. P.W. declares no conflicts of interest.

Developmental dysplasia of the hip (DDH) is one of the most common developmental deformities of the lower extremities, as well as one of the leading causes of early arthritis and total hip replacement.1 First-line therapy is most often the Pavlik harness,2,3 which has a reported rate of successful reduction of 63% to 93% for Ortolani-positive hips.4–6 Although hips typically stabilize within 3 to 4 weeks of initial Pavlik harness application, those that fail to achieve a stable reduction within this timeframe may be at increased risk for “Pavlik harness disease.”7 First defined by Jones et al,8 Pavlik harness disease is “prolonged positioning of the dislocated hip in flexion and abduction that potentiates dysplasia, particularly of the posterolateral acetabulum, and increases the difficulty of obtaining a stable closed reduction.” As a consequence, prolonged harness use in the setting of a persistent dislocation is thought to result in a greater proportion of patients requiring open reduction.9 It has thus become dogma to abandon harness treatment after 2 to 4 weeks if a hip remains unstable.5,7,9–12

ulty of obtaining a stable closed reduction.” As a consequence, prolonged harness use in the setting of a persistent dislocation is thought to result in a greater proportion of patients requiring open reduction.9 It has thus become dogma to abandon harness treatment after 2 to 4 weeks if a hip remains unstable.5,7,9–12 To our knowledge, however, no studies have documented objective morphologic changes to the acetabulum over time in response to continued treatment of an irreducible or unstable hip. Instead, the evidence in support of Pavlik harness disease originates from several small case series describing observational evidence of posterolateral acetabular insufficiency and surrogate markers such as increased rates of open reduction. Therefore, the purpose of this study was to investigate whether the acetabular α angle (AA) deteriorates with prolonged treatment of a dislocated hip with a Pavlik harness, and to determine the clinical outcome of those hips that fail prolonged harness therapy. METHODS This was a retrospective case series combining patients from a large tertiary-care children’s hospital (group A) and a multicenter, international study group (group B). Institutional review board approval was obtained before this study (group A) and for participation in the study group (group B).

To our knowledge, however, no studies have documented objective morphologic changes to the acetabulum over time in response to continued treatment of an irreducible or unstable hip. Instead, the evidence in support of Pavlik harness disease originates from several small case series describing observational evidence of posterolateral acetabular insufficiency and surrogate markers such as increased rates of open reduction. Therefore, the purpose of this study was to investigate whether the acetabular α angle (AA) deteriorates with prolonged treatment of a dislocated hip with a Pavlik harness, and to determine the clinical outcome of those hips that fail prolonged harness therapy. METHODS This was a retrospective case series combining patients from a large tertiary-care children’s hospital (group A) and a multicenter, international study group (group B). Institutional review board approval was obtained before this study (group A) and for participation in the study group (group B). At the primary institution, infants who fail Pavlik treatment are advanced to either an Ilfeld-style abduction orthosis or operative reduction/spica casting. Therefore, we queried our records to identify a consecutive series of infants with DDH who were prescribed a rigid abduction orthosis at our center from 2009 to 2015. Current Procedural Terminology codes for closed and open reduction for DDH (27257-9) were also utilized to identify a consecutive series of infants treated with operative hip reduction (Fig. 1A). For both cohorts, records were reviewed to identify all patients who had previously failed Pavlik harness treatment. Per the treating surgeon, Pavlik failure was defined as lack of progressive improvement in ultrasonographic indices and/or clinical examination over a minimum 3-week treatment period leading to discontinuation of the harness. A convenience sample was then established using the following exclusion criteria: no diagnosis of DDH, DDH of congenital, syndromic, and/or neuromuscular origin, above 6 months of age at time of Pavlik initiation, and incomplete availability of ultrasonographic imaging and/or clinical documentation. As details of therapy could not be verified, patients who failed Pavlik treatment at an outside institution were also excluded.

f congenital, syndromic, and/or neuromuscular origin, above 6 months of age at time of Pavlik initiation, and incomplete availability of ultrasonographic imaging and/or clinical documentation. As details of therapy could not be verified, patients who failed Pavlik treatment at an outside institution were also excluded. FIGURE 1 CONSORT (Consolidated Standards of Reporting Trials) diagram showing patients evaluated, excluded, and enrolled in (A) group A and (B) group B. Consistent with agreed-upon standards, hip dislocation was defined as <35% femoral head coverage (FHC) on the coronal flexion ultrasonographic views.13–15 To isolate a cohort of “persistently” dislocated hips and exclude those that may have been improving with treatment, we included only those hips with ≤35% FHC both at Pavlik initiation and termination. At our institution, not all infants receive an ultrasound before Pavlik initiation (eg, <1 mo old with an Ortolani-positive hip). To provide a sufficient imaging interval to capture morphologic changes to the acetabulum, patients with <3 weeks between first and final ultrasound were excluded. For all enrolled infants, outpatient records were reviewed to determine baseline demographic information, birth presentation, family history, and relevant clinical data at the time of Pavlik initiation. Each affected hip was categorized as irreducible or reducible (Ortolani positive) per physical examination and ultrasonographic stress testing.

outpatient records were reviewed to determine baseline demographic information, birth presentation, family history, and relevant clinical data at the time of Pavlik initiation. Each affected hip was categorized as irreducible or reducible (Ortolani positive) per physical examination and ultrasonographic stress testing. At the time of Pavlik initiation, parents were instructed to maintain the harness full time with/without the exception of bathing and diaper changes per treating surgeon preference. Infants were subsequently monitored with serial ultrasound and physical examination at 1- to 3-week intervals. At the time of Pavlik discontinuation, total time in harness was noted. Outpatient records were again reviewed to reclassify the clinical stability of each affected hip. Lastly, follow-up records were reviewed to determine the final means of obtaining a stable reduction for each hip (eg, closed reduction, open reduction, etc.).

me of Pavlik discontinuation, total time in harness was noted. Outpatient records were again reviewed to reclassify the clinical stability of each affected hip. Lastly, follow-up records were reviewed to determine the final means of obtaining a stable reduction for each hip (eg, closed reduction, open reduction, etc.). To identify additional patients, the deidentified database of a multicenter, international study group on hip dysplasia was queried for all patients below 6 months of age who were treated in Pavlik harness for DDH and had the harness discontinued because of instability and/or persistent dislocation (group B) (Fig. 1B). In addition to excluding those with undocumented length of time in Pavlik harness and/or undocumented AA/FHC, patients in group B were screened using identical exclusion criteria as group A. All data points previously described for group A were noted and directly recorded from the database for each patient in group B. The combined cohort (group A+B) was used for all further analyses.

Pavlik harness and/or undocumented AA/FHC, patients in group B were screened using identical exclusion criteria as group A. All data points previously described for group A were noted and directly recorded from the database for each patient in group B. The combined cohort (group A+B) was used for all further analyses. The primary outcomes, AA (Graf angle) and FHC, were measured for each affected hip on the first and final ultrasound in Pavlik harness. For group A, all measurements were made by the first author (A.L.G.) on the coronal flexion view. To determine interrater reliability, a random subset of 20 group A hips was independently measured in a blinded manner by the senior author (W.N.S.). A consensus measurement was then reached for each AA that differed between the raters by >3 degrees or each FHC that differed by >5%. Given excellent overall agreement for these 20 hips (interrater intraclass correlation coefficients for AA and FHC measurements, all >0.920), the primary observer’s measurements were used for the remaining hips (n=11) in group A. For group B, AA and FHC were measured by the individual treating surgeon at each center and directly entered into the database.

these 20 hips (interrater intraclass correlation coefficients for AA and FHC measurements, all >0.920), the primary observer’s measurements were used for the remaining hips (n=11) in group A. For group B, AA and FHC were measured by the individual treating surgeon at each center and directly entered into the database. Statistical Analysis Categorical variables were analyzed using the Fisher exact/χ2 tests. Continuous variables were assessed using the Shapiro-Wilk test and subsequently analyzed using either paired Student t tests, the Wilcoxon signed-rank test, or the Mann-Whitney U test. Intraclass correlation coefficient was determined using a 2-way mixed-effects model. Spearman correlations were used to evaluate the association between continuous variables. Linear regression was used to predict total change in AA when holding other patient characteristics and treatment details constant. An α level of 0.05 was used for all tests. RESULTS Our combined series consisted of 49 hips in 38 patients from 6 institutions (Fig. 1). Except for a higher proportion of patients with bilateral DDH in group A, there were no differences in baseline characteristics between the 2 groups (Table 1). Median age at Pavlik initiation was 4 weeks (range, 0 to 18 wk), with details of Pavlik harness treatment presented in Table 2. There were 20 patients (40%) treated for >5 weeks in harness between first and final ultrasound, of which 4 (8%) were treated for >10 weeks. TABLE 1 Demographics and Baseline Variables TABLE 2 Details of Pavlik Harness Treatment

RESULTS Our combined series consisted of 49 hips in 38 patients from 6 institutions (Fig. 1). Except for a higher proportion of patients with bilateral DDH in group A, there were no differences in baseline characteristics between the 2 groups (Table 1). Median age at Pavlik initiation was 4 weeks (range, 0 to 18 wk), with details of Pavlik harness treatment presented in Table 2. There were 20 patients (40%) treated for >5 weeks in harness between first and final ultrasound, of which 4 (8%) were treated for >10 weeks. TABLE 1 Demographics and Baseline Variables TABLE 2 Details of Pavlik Harness Treatment Surprisingly, we found an overall mean improvement of 4 degrees in AA and a mean increase in FHC of 1% between first and final ultrasound in harness (Table 3 and Fig. 2) Patients in groups A and B did not differ in terms of total change in AA (P=0.942). There was no significant difference in mean change in AA between those in harness <5 weeks (4±7 degrees) and those with prolonged harness wear ≥5 weeks (4±9 degrees) (P=0.521). Over the study period, 30/49 hips (61%) exhibited an increase in AA, 15 hips (31%) a decrease in AA, and 4 hips (8%) no change. There was no difference in any baseline characteristics or markers of disease severity, including femoral head reducibility and FHC, between hips with either no change or increases in AA versus those with decreases in AA (Table 4). TABLE 3 Change in Ultrasonographic Measurements Between First and Final US in Harness

Surprisingly, we found an overall mean improvement of 4 degrees in AA and a mean increase in FHC of 1% between first and final ultrasound in harness (Table 3 and Fig. 2) Patients in groups A and B did not differ in terms of total change in AA (P=0.942). There was no significant difference in mean change in AA between those in harness <5 weeks (4±7 degrees) and those with prolonged harness wear ≥5 weeks (4±9 degrees) (P=0.521). Over the study period, 30/49 hips (61%) exhibited an increase in AA, 15 hips (31%) a decrease in AA, and 4 hips (8%) no change. There was no difference in any baseline characteristics or markers of disease severity, including femoral head reducibility and FHC, between hips with either no change or increases in AA versus those with decreases in AA (Table 4). TABLE 3 Change in Ultrasonographic Measurements Between First and Final US in Harness FIGURE 2 Case example of a 6-week-old female with developmental dysplasia of the left hip. A, Initial ultrasound before Pavlik harness initiation demonstrates a left hip dislocation. B, Follow-up ultrasound after 12 weeks in harness demonstrates persistent dislocation but similar acetabular morphology. Of note, the hip was Ortolani positive on clinical exam at both Pavlik initiation and termination. Following Pavlik harness failure, the patient was treated successfully with closed reduction and spica casting. TABLE 4 Comparison of Disease Characteristics Between Hips With Either an Increase in AA or No Change Over Treatment Period Versus Hips With a Decrease in AA

FIGURE 2 Case example of a 6-week-old female with developmental dysplasia of the left hip. A, Initial ultrasound before Pavlik harness initiation demonstrates a left hip dislocation. B, Follow-up ultrasound after 12 weeks in harness demonstrates persistent dislocation but similar acetabular morphology. Of note, the hip was Ortolani positive on clinical exam at both Pavlik initiation and termination. Following Pavlik harness failure, the patient was treated successfully with closed reduction and spica casting. TABLE 4 Comparison of Disease Characteristics Between Hips With Either an Increase in AA or No Change Over Treatment Period Versus Hips With a Decrease in AA Looking further at potential moderating factors, Spearman correlations revealed no statistically significant linear association between change in AA and time in harness between ultrasounds (P=0.545; Fig. 3), age at Pavlik harness initiation (P=0.105), FHC at first ultrasound (P=0.956), or FHC at final ultrasound (P=0.651). Independent regressions indicated that bilateral disease, family history of DDH, history of breech presentation, femoral head reducibility, and FHC at initial/final ultrasound did not significantly predict change in AA when controlling for length of time in harness (all P’s> 0.05). Furthermore, length of time in harness did not by itself significantly predict total change in AA when separately controlling for each of these above variables (all P’s> 0.05).

and FHC at initial/final ultrasound did not significantly predict change in AA when controlling for length of time in harness (all P’s> 0.05). Furthermore, length of time in harness did not by itself significantly predict total change in AA when separately controlling for each of these above variables (all P’s> 0.05). FIGURE 3 Scatterplot depicting change in α angle over length of time in Pavlik harness (Spearman ρ=0.089). Given these findings, there is no evidence of a statistically significant association between change in α angle and length of time in Pavlik harness (P=0.545). Following harness failure, 38 hips were treated with a trial of rigid abduction bracing, of whom 22 (58% of those treated in-brace; 45% overall) stabilized and required no further treatment (Table 5). Sixteen hips (33%) were treated successfully with closed reduction/spica casting and 10 (20%) required open reduction; 1 hip (2%) spontaneously reduced and required no further treatment. Only 1 patient (2%) required a revision open reduction following the initial attempt. In total, 39/49 hips (80%) were successfully reduced through closed means, with no significant differences between those with a decrease in AA versus those that improved or remained stable (P=0.702), and no differences between those in harness <5 weeks versus those ≥5 weeks (83% vs. 75%; P=0.720). TABLE 5 Final Means of Obtaining a Concentric Reduction Following Failure of Pavlik Harness Therapy

Following harness failure, 38 hips were treated with a trial of rigid abduction bracing, of whom 22 (58% of those treated in-brace; 45% overall) stabilized and required no further treatment (Table 5). Sixteen hips (33%) were treated successfully with closed reduction/spica casting and 10 (20%) required open reduction; 1 hip (2%) spontaneously reduced and required no further treatment. Only 1 patient (2%) required a revision open reduction following the initial attempt. In total, 39/49 hips (80%) were successfully reduced through closed means, with no significant differences between those with a decrease in AA versus those that improved or remained stable (P=0.702), and no differences between those in harness <5 weeks versus those ≥5 weeks (83% vs. 75%; P=0.720). TABLE 5 Final Means of Obtaining a Concentric Reduction Following Failure of Pavlik Harness Therapy DISCUSSION The Pavlik harness is the treatment of choice for most infants with a developmental dislocation of the hip under 6 months of age. For those that do not respond to Pavlik treatment, concerns exist that prolonged use of the harness in the setting of a persistent dislocation can result in “Pavlik harness disease,” or erosion of the posterior acetabulum, making subsequent hip reduction more challenging.7–10 Accordingly, current recommendations are to carefully monitor progress for 2 to 4 weeks before abandoning harness treatment of a persistently dislocated hip.5,7,9–12 Given the deep-rooted nature of this dogma, no recent studies have evaluated Pavlik harness disease, and very few patients, if any, are ever maintained in harness for prolonged periods of time.

e to carefully monitor progress for 2 to 4 weeks before abandoning harness treatment of a persistently dislocated hip.5,7,9–12 Given the deep-rooted nature of this dogma, no recent studies have evaluated Pavlik harness disease, and very few patients, if any, are ever maintained in harness for prolonged periods of time. The actual evidence to support Pavlik harness disease, however, is surprisingly limited. Early case series guiding current recommendations described findings from hips treated for significantly longer than 2 to 4 weeks. The mean duration of harness use in Jones et al8 study was 16 weeks (range, 8 wk to 15 mo), with 7/19 (37%) treated for 15 weeks or longer. In addition, their descriptions of posterolateral acetabular deficiency were purely observational, and in those infants treated in harness for <10 weeks, only 1 (20%) required an open reduction. Similarly, Viere et al9 reported on 30 hips that were treated for a mean of 8 weeks (range, 3 to 23 wk), with only 4 hips requiring an additional procedure; there was no difference in mean length of preceding harness use between those treated successfully with closed reduction and those requiring an open reduction. Reviewing this evidence, Harding et al12 concluded that the 2- to 4-week guideline is more so associated with a lack of adverse outcomes and a fear of causing iatrogenic damage than direct evidence of negative morphologic changes. To our knowledge, no previous studies have attempted to evaluate objective morphologic changes to the acetabulum in response to continued Pavlik treatment of a persistently dislocated hip.

iated with a lack of adverse outcomes and a fear of causing iatrogenic damage than direct evidence of negative morphologic changes. To our knowledge, no previous studies have attempted to evaluate objective morphologic changes to the acetabulum in response to continued Pavlik treatment of a persistently dislocated hip. In fact, recent evidence suggests that prolonged harness treatment may be beneficial in certain cases. In a prospective study, van der Sluijs et al16 reported that 77% of their Graf type-III hips that went on to achieve reduction with harness treatment did so after 6 weeks, suggesting that treatment may be continued in those patients with improving hip abduction and ultrasonographic indices. In a qualitative study, Senaran et al17 noted that 32/35 hips that failed Pavlik harness treatment had a stable and/or improved sonographic grade at treatment termination as measured by femoral head position and stability. Taylor and Clarke18 agreed, noting that it is important to utilize ultrasound to fully distinguish the gradually improving subluxed hip from the irreducible one. Conversely, operative hip reduction introduces a number of significant concerns, including exposure to general anesthesia, challenges from spica cast care, and an increased risk for iatrogenic avascular necrosis and its accompanying impact on long-term outcomes and function.19,20

subluxed hip from the irreducible one. Conversely, operative hip reduction introduces a number of significant concerns, including exposure to general anesthesia, challenges from spica cast care, and an increased risk for iatrogenic avascular necrosis and its accompanying impact on long-term outcomes and function.19,20 Anecdotal experience from our institution suggests that subsequent treatment has not been compromised by continued use of the harness beyond the 2- to 4-week recommendation. Therefore, we sought to begin to question the concept of Pavlik harness disease by investigating potential changes to the AA that may result from continued treatment of a persistently dislocated hip. Surprisingly, our results demonstrated a slight mean improvement in both AA and FHC for hips that remained dislocated through a minimum 3-week treatment period. In terms of clinical significance, we do not interpret our results to mean that continued Pavlik harness use for a persistently dislocated hip is beneficial for the acetabulum. It is possible that the observed “improvement” in AA was due to some positive development of the acetabulum even in the absence of a concentric reduction.21 Regardless, our data do suggest that in a properly monitored hip, continued Pavlik use beyond current recommendations may be reasonable, and at the very least, it may not always be deleterious. It should be noted, however, that some hips in our series did demonstrate deteriorations in AA, implying that blind use of a harness for prolonged periods of time may indeed be harmful for certain hips. Although we did not ascertain any significant predictors for this behavior, proper monitoring (using serial ultrasound) would identify these select hips, and allow continued safe use of the harness in others, especially for those showing progressive improvement in clinical exam and/or ultrasonographic indices. Perhaps most importantly, unsuccessful harness treatment did not seem to adversely affect treatment outcomes, as 80% of hips in our cohort were reduced successfully using closed means, and only 1 hip failed open reduction and required revision surgery.

ssive improvement in clinical exam and/or ultrasonographic indices. Perhaps most importantly, unsuccessful harness treatment did not seem to adversely affect treatment outcomes, as 80% of hips in our cohort were reduced successfully using closed means, and only 1 hip failed open reduction and required revision surgery. Previous studies have reported rates of open reduction for infants aged 1 month and below at Pavlik initiation who went on to fail harness treatment. Tiruveedhula et al22 noted in a prospective study of 37 hips that 46% required an open reduction. Novais et al23 reported on 215 hips treated in Pavlik harness, including 30 that failed treatment. Of these, 8 (27%) required open treatment, all of which were initially Ortolani positive. Ibrahim et al24 reported an open reduction rate of 43% for their 7 hips that were braced after failed Pavlik, although the mean age at harness initiation was slightly older at 2.1 months. In contrast, Hedequist et al25 reported that all 15 of their hips that were treated with a rigid abduction orthosis following failed Pavlik were eventually reduced through closed means, and Senaran et al17 noted that only 2 of their 35 hips (6%) that failed Pavlik required an open reduction. However, it should be noted that only 46% of the hips in Senaran’s series were dislocated by ultrasound at Pavlik termination. In summary, our observed open reduction rate of 20% compares favorably to the published literature, further suggesting that prolonged harness treatment in this cohort did not seem to compromise subsequent treatment.

noted that only 46% of the hips in Senaran’s series were dislocated by ultrasound at Pavlik termination. In summary, our observed open reduction rate of 20% compares favorably to the published literature, further suggesting that prolonged harness treatment in this cohort did not seem to compromise subsequent treatment. This study has a number of limitations. First, we used AA as a global measure of acetabular morphology, but did not specifically measure the anatomic changes in the posterior wall. Unfortunately, no previous studies have described objective measures to evaluate posterior wall anatomy, and although we explored several possible measurement techniques, including transverse views, these were abandoned for poor reproducibility and lack of normative data. Consequently, using the AA as a global measure of acetabular morphology and tracking the clinical outcomes of those hips that fail harness therapy may be the best available method to indirectly account for the posterior wall changes purported to occur with Pavlik harness disease. In addition, we did not have data regarding the specific location of the femoral head for each dislocated hip (eg, perched, posterolateral, superior to transverse ligament, etc.), which may have influenced the risk of developing of Pavlik harness disease. Nevertheless, in this study, neither femoral head reducibility nor FHC affected change in AA, indicating that within the confines of our data, femoral head position seemed not to affect the risk of developing negative changes to the acetabulum.

which may have influenced the risk of developing of Pavlik harness disease. Nevertheless, in this study, neither femoral head reducibility nor FHC affected change in AA, indicating that within the confines of our data, femoral head position seemed not to affect the risk of developing negative changes to the acetabulum. In this study, the median length of time in harness between ultrasounds was only 4 weeks, although 40% were treated for >5 weeks. As a result, our data may not be generalizable to longer-term Pavlik use. Given the extreme dogma of Pavlik harness disease, however, it is nearly impossible either retrospectively or prospectively to identify a cohort of infants with persistent dislocations treated in a harness for longer periods than this study. Although the number of hips in this series was somewhat modest, a larger series would be challenging to isolate given the high success rate of Pavlik harness treatment. By pooling patients from a large, tertiary-care children’s hospital and a multicenter, international study group, we feel that the study cohort was as robust as feasibly allowed, and also more broadly representative of the general population. As a retrospective sample, our study was subject to inherent selection bias, as a predetermined criterion for Pavlik harness failure was not utilized. In addition, it is possible that the hips in this study were developing “better” than other hips failing harness treatment, which is why the treating surgeon felt comfortable continuing use of the Pavlik beyond the typical guidelines. To minimize this possibility, we used a consistent definition of a dislocation based on objective ultrasonographic criteria to ensure that hips were “similarly” dislocated both at Pavlik initiation and termination, thereby implying that no significant improvement occurred over the treatment period. Finally, a decision was made a priori only to follow patients until the point at which stable reduction was achieved, as this study’s primary objective was to investigate changes to the acetabulum during failed harness use and their potential effect on the ultimate means of reduction. We therefore cannot comment on the incidence of osteonecrosis or residual dysplasia following failed Pavlik treatment. Despite these limitations, we believe this study is an important first step toward objectively questioning a widely believed concept that has little supportive evidence.

he ultimate means of reduction. We therefore cannot comment on the incidence of osteonecrosis or residual dysplasia following failed Pavlik treatment. Despite these limitations, we believe this study is an important first step toward objectively questioning a widely believed concept that has little supportive evidence. In conclusion, based on the lengths of harness treatment in our series, most hips did not exhibit negative changes in the acetabular AA in response to prolonged treatment of a dislocated hip in Pavlik harness. Furthermore, the success of subsequent treatment was not compromised by extended use of the harness. With appropriate monitoring, therefore, prolonged management of a dislocated hip with Pavlik harness may have fewer adverse consequences than previously thought. Further investigation is required to definitively confirm or refute the presence of Pavlik harness disease. Study Conducted at the Children’s Hospital of Philadelphia in Conjunction With the International Hip Dysplasia Institute. Funding was received from the International Hip Dysplasia Institute for research support and study coordination. The authors declare no conflicts of interest.

The accurate assessment of skeletal maturity and growth is crucial for many decisions in pediatric orthopaedics such as the management of adolescent idiopathic scoliosis,1–3 the determination of when to stop growth using an epiphysiodesis, and the treatment of contralateral slipped capital femoral epiphysis.4,5 To assess these important metrics, a variety of systems have been developed. This began with the work of Todd et al6 in 1937 and includes the famous Greulich and Pyle atlas of the hand7–9 as well as the Tanner-Whitehouse III (TW-III) system.10,11 Unfortunately, many of these systems either did not take into account the timing of growth [the peak height velocity (PHV) age—PHV or peak growth age (PGA), both terms are used] or were too complicated for routine clinical use.12 Furthermore, increased awareness of the need to minimize radiation in children has suggested that maturity should be able to be assessed from any required x-ray image. Given these issues, the optimal methods for predicting the remaining growth and precise degree of skeletal maturity in children remains a pressing area of research.

increased awareness of the need to minimize radiation in children has suggested that maturity should be able to be assessed from any required x-ray image. Given these issues, the optimal methods for predicting the remaining growth and precise degree of skeletal maturity in children remains a pressing area of research. Fortunately, progress in addressing these issues has been seen in the development of site-specific staging systems. For example, previous work demonstrated a method of evaluating the hand that was based upon the TW-III system and was found to be more straightforward than the full system yet more accurate than either the Risser grading system or the Greulich and Pyle atlas.13–15 Similarly, our group has developed a method of skeletal maturity and growth determination based on ossification of the calcaneal apophysis that was found to be well distributed around PHV with excellent intraobserver and interobserver reliability.16,17 Despite these advances, no such method currently exists for evaluating the physes of the upper extremity that are captured in standard scoliosis spine films. In this study, we hypothesized that proximal humeral ossification would closely correlate with growth, could be staged with high interrater and intrarater reliability, and could be integrated with existing clinical classification systems to better understand growth.

Fortunately, progress in addressing these issues has been seen in the development of site-specific staging systems. For example, previous work demonstrated a method of evaluating the hand that was based upon the TW-III system and was found to be more straightforward than the full system yet more accurate than either the Risser grading system or the Greulich and Pyle atlas.13–15 Similarly, our group has developed a method of skeletal maturity and growth determination based on ossification of the calcaneal apophysis that was found to be well distributed around PHV with excellent intraobserver and interobserver reliability.16,17 Despite these advances, no such method currently exists for evaluating the physes of the upper extremity that are captured in standard scoliosis spine films. In this study, we hypothesized that proximal humeral ossification would closely correlate with growth, could be staged with high interrater and intrarater reliability, and could be integrated with existing clinical classification systems to better understand growth. METHODS The Brush Inquiry was a prospective, longitudinal assessment of growth conducted with 4435 children in Cleveland, OH between 1926 and 1942.18 The study was directed by Dr T. Wingate Todd of the Brush Foundation at Western Reserve University. These children were followed at least annually using serial radiographs of their skull and left-sided extremities including shoulder, elbow, wrist, hand, hip, knee and foot.16,18

in Cleveland, OH between 1926 and 1942.18 The study was directed by Dr T. Wingate Todd of the Brush Foundation at Western Reserve University. These children were followed at least annually using serial radiographs of their skull and left-sided extremities including shoulder, elbow, wrist, hand, hip, knee and foot.16,18 Notably, these radiographs were used by Greulich and Pyle in their landmark atlas of bone age using hand ossification and the same set has been used to describe other ossification markers.7,8 Furthermore, the data are enriched by anthropometric data such as height and weight that were recorded when the children presented for radiographs. Height was measured with a stadiometer using a standardized method meaning that measurements would be consistent between observers and over time. Children selected did not have any gross physical or mental defect and parental permission was granted for children to participate for the duration of the study.18,19 Here we identified a subset of 94 children (49 female, 45 male individuals) who had complete data with consecutive radiographs and height data performed at least annually between the ages of 10 and 15 years. This age range was selected because it corresponds with the PHV and therefore represents the usual age of decision making in managing adolescent idiopathic scoliosis.

45 male individuals) who had complete data with consecutive radiographs and height data performed at least annually between the ages of 10 and 15 years. This age range was selected because it corresponds with the PHV and therefore represents the usual age of decision making in managing adolescent idiopathic scoliosis. The PGA was defined by calculating growth velocity in centimeters per year and applying a cubic spline method to fit curves. The age at which the child went through PHV was then determined after the approach of Tanner and Davies. Determining PHV by this validated approach determines a single time point that represents the instant when the fastest rate of growth occurs.16 We also calculated percent growth remaining by comparing the standing height of the child at the time of radiograph and their final standing height measurement at age 18. Note that 10% of growth remaining occurs around PGA and is plotted in Figure 3. All other figures use the cubic spline method for PGA. Eight observers including 3 medical students, 3 residents, and 2 attending surgeons viewed randomly selected radiographs from 30 patients in order to assign a humeral head stage for each radiograph. Risser, triradiate closure, and hand systems were also determined during the same sets of radiographs using widely accepted guidelines. Cohen’s κ was calculated to determine intraobserver and interobserver reliability. Means and SDs were determined using pooled data from all observers. Stata was used for statistical analysis and plots were generated in Microsoft Excel.

lso determined during the same sets of radiographs using widely accepted guidelines. Cohen’s κ was calculated to determine intraobserver and interobserver reliability. Means and SDs were determined using pooled data from all observers. Stata was used for statistical analysis and plots were generated in Microsoft Excel. RESULTS A 5-stage humeral head classification system was developed based on the appearance of the lateral margin of the epiphysis (schematized in Fig. 1 with examples provided in Fig. 2). The earliest radiographs examined (on average 5.22 y before PHV) showed partial ossification of the humeral head epiphysis leaving an oblique lateral epiphyseal margin and a triangular area of radiolucency. Ossification then continued with rounding of the lateral margin (on average 1.54 y before PHV) that continued via lateral epiphyseal growth until the margin became colinear to the metaphysis (on average 0.58 y after PHV). Partial and complete fusion of the physis then followed (on average 2.27 and 4.02 y after PHV, respectively) (Fig. 3).

ntinued with rounding of the lateral margin (on average 1.54 y before PHV) that continued via lateral epiphyseal growth until the margin became colinear to the metaphysis (on average 0.58 y after PHV). Partial and complete fusion of the physis then followed (on average 2.27 and 4.02 y after PHV, respectively) (Fig. 3). FIGURE 1 Periphyseal changes around the proximal humerus: stage 1 demonstrates an incompletely ossified lateral epiphysis such that the lateral margin is oblique (short bold line). Stage 2 demonstrates increased ossification of the lateral epiphysis with a curvilinear lateral margin (bold curve). Note that in stages 1 and 2, the bold line parallel to the lateral metaphysis does not touch the epiphysis. Stages 3 through 5 all demonstrate colinearity between the lateral margin of the epiphysis and the metaphysis such that a single bold line touches both edges. In stage 3, the lateral half of the physis is open without obvious fusion. In stage 4, the lateral half of the physis thins and begins partial fusion. Finally, by stage 5 the lateral half of the physis demonstrates essentially complete fusion. Fusion is indicated by the hashes.

at a single bold line touches both edges. In stage 3, the lateral half of the physis is open without obvious fusion. In stage 4, the lateral half of the physis thins and begins partial fusion. Finally, by stage 5 the lateral half of the physis demonstrates essentially complete fusion. Fusion is indicated by the hashes. FIGURE 2 Representative images of the humeral stages. Stage 1 demonstrates an incompletely ossified lateral epiphysis leaving a triangular area of radiolucency on the lateral aspect of the epiphysis. Stage 2 demonstrates increased ossification of the lateral epiphysis leaving a crescent shaped area of radiolucency on the lateral side of the epiphysis. These shapes are highlighted below the annotations with representative images shown both unmodified and with the shapes superimposed. Note that in stages 1 and 2, the black line parallel to the lateral metaphysis does not touch the epiphysis. Stages 3 through 5 all demonstrate colinearity between the lateral margin of the epiphysis and the metaphysis. In Stage 3, the lateral half of the physis is open without obvious fusion. In stage 4, the lateral half of the physis thins and begins partial fusion. Finally, by stage 5 the lateral half of the physis demonstrates essentially complete fusion. The same annotations used on the schematic are superimposed upon the radiographic examples for ease of comparison.

ysis is open without obvious fusion. In stage 4, the lateral half of the physis thins and begins partial fusion. Finally, by stage 5 the lateral half of the physis demonstrates essentially complete fusion. The same annotations used on the schematic are superimposed upon the radiographic examples for ease of comparison. FIGURE 3 Normalized distribution of staging with age to PHV (years) on the x-axis and proportion of observations on the y-axis. A vertical line is drawn at PHV occurring between stages 2 and 3. PHV indicates peak height velocity. In 72% of cases, PGA occurred within 1 year of the transition between stages 2 and 3. The remaining stages were well distributed both before and after the critical age of PHV. In order to place this novel system in the appropriate clinical context, well characterized standards were plotted against the humeral system (Fig. 4). From this plot we observe that the transition between stages 1 and 2 is the earliest indicator that a patient is approaching PHV. The transition between 2 and 3 also slightly precedes PHV. The humerus system was also found to be reliable when tested by investigators of diverse experience levels from high school to attending surgeon. In total, 84% of observations had perfect agreement and no set of observations differed by >1 stage. For intraobserver comparisons, κ was 0.80 and intraclass correlation coefficient was 0.96. For interobserver comparisons, κ was 0.78 and intraclass correlation coefficient was 0.95.

rom high school to attending surgeon. In total, 84% of observations had perfect agreement and no set of observations differed by >1 stage. For intraobserver comparisons, κ was 0.80 and intraclass correlation coefficient was 0.96. For interobserver comparisons, κ was 0.78 and intraclass correlation coefficient was 0.95. FIGURE 4 Humeral head ossification system placed in context of currently used standards for the determination of skeletal maturity including TRC, iliac apophysis ossification (Risser), hand scoring systems, and menarche. Boxes are indicated based on the stage containing the plurality of data at that time point. All ossification systems were measured on the same patients used to develop our humeral head staging system. Menarche for this dataset is likely unreliable for modern patients so a modern standard from our previous work has been used. Time relative to PGA was measured in years. PGA indicates peak growth age; TRC, triradiate cartilage closure. As regards growth remaining, on average, patients with x-rays categorized as stage 1 had 26% (SD, 7%) of their growth remaining. Patients in stage 2 had an average of 16% of their growth remaining (SD, 5%). Patients in stage 3 had 7% growth remaining on average (SD, 4%), while patients in stage 4 had an average of 2% of growth remaining (SD, 3%). Patients in stage 5 had only 0.5% of their growth remaining on average (SD, 2%). Therefore, we found that the humeral head stages were well distributed across growth remaining (Fig. 5).

s in stage 3 had 7% growth remaining on average (SD, 4%), while patients in stage 4 had an average of 2% of growth remaining (SD, 3%). Patients in stage 5 had only 0.5% of their growth remaining on average (SD, 2%). Therefore, we found that the humeral head stages were well distributed across growth remaining (Fig. 5). FIGURE 5 Humeral head staging system with regard to percentage of growth remaining in patients as determined by current standing height versus final standing height. Note that PHV usually occurs around 90% of growth completed and is indicated by the horizontal line. PHV indicates peak height velocity. Finally, the distinctness of each humeral head stage with regards to growth remaining was determined by determining the degree of overlap between adjacent stages. The humeral head stages overlapped very little with one another with between 13% and 27% of data crossing into the interquartile ranges of adjacent stages. In contrast, the Risser sign had between 20% and 87% data that overlapped into the interquartile ranges of adjacent stages (Table 1). TABLE 1 Percentage of Overlap Between Adjacent Stages in Both Systems DISCUSSION Scoliosis is an important pediatric orthopaedic condition that affects 0.5% to 5% of adolescents20–22 and is associated with increased morbidity and mortality due to major spinal deformity, restrictive lung disease, and postoperative complications.23,24 Bracing and surgery for scoliosis are major interventions that can affect the quality of life for adolescents and cost up to $5000 for bracing or $100,000 for surgery.25,26

is associated with increased morbidity and mortality due to major spinal deformity, restrictive lung disease, and postoperative complications.23,24 Bracing and surgery for scoliosis are major interventions that can affect the quality of life for adolescents and cost up to $5000 for bracing or $100,000 for surgery.25,26 Selecting the proper treatment course for patients with scoliosis is therefore an important pediatric orthopaedic imperative; however, tools currently available for assessing maturity that guides treatment decision making have major limitations. For example, the Risser sign does not cover the period around peak growth where the most critical curve progression occurs and hand staging systems require additional radiation.15 The development of a reliable tool that does not require additional radiation represents a significant advance in determining maturity and directing the treatment of patients with scoliosis.

riod around peak growth where the most critical curve progression occurs and hand staging systems require additional radiation.15 The development of a reliable tool that does not require additional radiation represents a significant advance in determining maturity and directing the treatment of patients with scoliosis. Our group has previously shown that novel markers based on periphyseal ossification can be used to reliably predict the PGA and the percent of growth remaining.17 Here, we show that the proximal humerus provides one such potential marker of growth that can be used to accurately determine growth in the treatment of scoliosis. Specifically, we demonstrate that proximal humeral ossification closely correlates with both age of PGA and % growth remaining, features much less overlap between stages compared with the Risser system, and can be implemented by providers with a broad range of experience with high interrater and intrarater reliability. Therefore, we conclude that this novel classification system can be learned easily by physicians and provides additional information about skeletal maturity. The position can also be easily understood by radiology technicians because it is seen with the hands by the sides and the palms facing forwards. Furthermore, since a view of the humeral head is almost always present on standard scoliosis spine x-ray at our institution we believe that this classification system will improve care without increasing radiation, time, or cost.

technicians because it is seen with the hands by the sides and the palms facing forwards. Furthermore, since a view of the humeral head is almost always present on standard scoliosis spine x-ray at our institution we believe that this classification system will improve care without increasing radiation, time, or cost. A possible limitation of this study is the historical collection of radiographs; however the suggestion that these patients are not representative because children now reach puberty at an earlier age is not accurate as our system compares PHV and growth remaining to skeletal maturity rather than chronological age.12,27,28 Specifically, a calcaneal classification that we developed with the same collection matched well with a modern cohort.17,27 Furthermore, there may also be concerns that children in the Bolton Brush study were more likely to be malnourished; however, the selection of participants included criteria such as good health. Finally, although growth remaining values are presented for each stage in this study, the values for stages 1 and 5 should be interpreted with caution, as they are influenced by the age range used in the study.

more likely to be malnourished; however, the selection of participants included criteria such as good health. Finally, although growth remaining values are presented for each stage in this study, the values for stages 1 and 5 should be interpreted with caution, as they are influenced by the age range used in the study. Development of a staging system involving the proximal humeral physis represents a novel approach to the evaluation of skeletal maturity in scoliosis patients that can eliminate the need to obtain additional x-rays and provides better stratification of patients among treatment algorithms. In particular, we believe that this system will be effective in the evaluation of Risser 0, premenarchal patients. We are currently in the process of conducting a companion study of this system using a retrospective review of modern scoliosis patients to determine the effects of using this system in determining curve progression and effectiveness of bracing. Ultimately, the proximal humeral physis skeletal maturity system is an innovative and impactful method to assist scoliosis surgeons in the evaluation of skeletal maturity. The authors declare no conflicts of interest.

Reporting surgical adverse events (AEs) is a critical component of surgical outcome studies but does not always receive adequate methodological rigor. Just over 20 years ago, the editor of the Lancet identified poor study design and lack of standardization in the reporting of safety and outcomes relevant to patients, as areas of major concern in surgical literature.1 In an effort to address this, Clavien and Dindo developed a valid and reliable classification system for AEs in general surgery,2–4 which is perceived similarly by patients, nurses, and physicians.5 In its first orthopaedic application, Sink et al6 modified the Clavien-Dindo system (MCD) for hip preservation surgery and showed good interrater and intrarater reliability. Until now, there has been no standardized system for reporting the severity of AEs in orthopaedic surgery and little is known about the reliability of reporting AEs in complex neurological conditions, such as cerebral palsy (CP).6,7

CD) for hip preservation surgery and showed good interrater and intrarater reliability. Until now, there has been no standardized system for reporting the severity of AEs in orthopaedic surgery and little is known about the reliability of reporting AEs in complex neurological conditions, such as cerebral palsy (CP).6,7 A retrospective matched cohort study by DiFazio et al8 utilized the MCD for reporting postoperative complications after hip surgery in nonambulant children with CP compared with children without CP. The study showed that children with CP had more frequent AEs than children without CP, and had a different profile of AEs.8 In children without CP, surgical AEs such as delayed union, wound hematomas and neuropraxias were the most common complications. In children with CP, skin complications were frequent as were medical AEs including gastrointestinal and respiratory complications.8 Most recently, Dreher et al9 utilized the MCD in a long-term multicenter retrospective study, reporting the outcomes of surgery to improve gait in ambulant children with CP. Nearly half of the children suffered from an AE, most of which were self-limiting. The use of the MCD as a formal tool to report surgical AEs was commended by Theologis,10 in a commentary for the study by Dreher et al.9

retrospective study, reporting the outcomes of surgery to improve gait in ambulant children with CP. Nearly half of the children suffered from an AE, most of which were self-limiting. The use of the MCD as a formal tool to report surgical AEs was commended by Theologis,10 in a commentary for the study by Dreher et al.9 We have also found the MCD by Sink et al6 to be useful for reporting AEs following orthopaedic surgery in children with CP. Given that the AE profiles of children with CP and typically developing children are very different, further minor modifications and clarifications appropriate for use in children with CP were considered to be required,8 along with evaluating the reliability of this modified MCD for use in children with CP. The aim of the study was to evaluate the interrater and intrarater reliability of the MCD of AEs for use in CP after lower limb orthopaedic surgery, and to determine if the MCD was a tool that could be easily used by medical and health professionals in a multidisciplinary setting, and be understood and acceptable to individuals with CP and their families.

the interrater and intrarater reliability of the MCD of AEs for use in CP after lower limb orthopaedic surgery, and to determine if the MCD was a tool that could be easily used by medical and health professionals in a multidisciplinary setting, and be understood and acceptable to individuals with CP and their families. METHODS Developing a MCD System for CP The MCD is a 5-grade ordinal system (Table 1), with grading determined by the treatment required to manage the AE and any associated long-term morbidity. We based our MCD on modifications made by Sink et al6 to the CD, in combination with the profile of AEs experienced by children with CP after orthopaedic surgery in recently reported studies.7,8 Using information from these studies, we made several customizations to the MCD to increase its applicability to children with CP (Table 1, Appendix 1, Supplemental Digital Content 1, http://links.lww.com/BPO/A170). TABLE 1 Summary of Definitions of Each Grade of the Modified Clavien-Dindo System, Modified for Children With Cerebral Palsy, including examples for each grade Participants We identified and invited 18 multidisciplinary members who worked closely within a team and were willing to participate in the ratings of 40 clinical scenarios related to children with CP who had undergone orthopaedic surgery at a single tertiary pediatric center. The panel of raters comprised of the following:Eight orthopaedic surgeons (3 attendings with fellowship training in pediatric orthopaedics, 3 clinical fellows in pediatric orthopaedics, and 2 research fellows).

rios related to children with CP who had undergone orthopaedic surgery at a single tertiary pediatric center. The panel of raters comprised of the following:Eight orthopaedic surgeons (3 attendings with fellowship training in pediatric orthopaedics, 3 clinical fellows in pediatric orthopaedics, and 2 research fellows). Five senior physical therapists who were working in a gait laboratory or hip surveillance service. Two senior clinical nurse coordinators, with both ward and outpatient experience. Three young adults with CP who had previously experienced orthopaedic surgery and who were currently working in the medical field.

rios related to children with CP who had undergone orthopaedic surgery at a single tertiary pediatric center. The panel of raters comprised of the following:Eight orthopaedic surgeons (3 attendings with fellowship training in pediatric orthopaedics, 3 clinical fellows in pediatric orthopaedics, and 2 research fellows). Five senior physical therapists who were working in a gait laboratory or hip surveillance service. Two senior clinical nurse coordinators, with both ward and outpatient experience. Three young adults with CP who had previously experienced orthopaedic surgery and who were currently working in the medical field. Reliability Ratings We drew upon the experience of Sink et al6 to determine the number of clinical scenarios required for the study. Forty clinical scenarios were created from complications recorded over a 20-year period in our tertiary center, which provides surgical care for a large population of children with CP. Scenarios were aimed to reflect a combination of recently published AEs.7–9 Each scenario was based on a specific patient and real clinical events with a minimum 2-year follow-up to be certain about long-term outcomes. Information included age, sex, Gross Motor Function Classification System level, clinical and operative information, details about the AE, management of the AE, and long-term outcome. Clinical photographs or radiographs, which had been archived from the time of the AE, were used to illustrate each scenario. The clinical scenarios were presented in PowerPoint (Appendix 2, Supplemental Digital Content 2, http://links.lww.com/BPO/A171). All MCD grades were represented across the scenarios, but they did not reflect the frequency of MCD grades from previous studies (Fig. 1).7,8 Patient data was deidentified and institutional privacy regulations observed.

presented in PowerPoint (Appendix 2, Supplemental Digital Content 2, http://links.lww.com/BPO/A171). All MCD grades were represented across the scenarios, but they did not reflect the frequency of MCD grades from previous studies (Fig. 1).7,8 Patient data was deidentified and institutional privacy regulations observed. FIGURE 1 Distribution of graded MCD adverse events used for clinical scenario ratings. MCD indicates modified Clavien-Dindo system. Immediately before the first rating, a meeting was held with all raters to provide orientation to the MCD. All raters were presented with material to familiarize them with the MCD for CP, including a detailed description of the study purpose and the MCD (Appendix 3, Supplemental Digital Content 3, http://links.lww.com/BPO/A172). Four example scenarios were provided for each MCD grade and discussed. Using skin-related AEs as a specific example, a priori discussion with raters agreed on the following:Grade I—skin redness or irritation from a cast or splint which is resolved by a simple adjustment. Grade II—a partial thickness skin breakdown which required outpatient dressings. Grade III—the presence of a full thickness ulcer, requiring surgical debridement, skin grafting, or a skin flap, under general anesthesia.

Immediately before the first rating, a meeting was held with all raters to provide orientation to the MCD. All raters were presented with material to familiarize them with the MCD for CP, including a detailed description of the study purpose and the MCD (Appendix 3, Supplemental Digital Content 3, http://links.lww.com/BPO/A172). Four example scenarios were provided for each MCD grade and discussed. Using skin-related AEs as a specific example, a priori discussion with raters agreed on the following:Grade I—skin redness or irritation from a cast or splint which is resolved by a simple adjustment. Grade II—a partial thickness skin breakdown which required outpatient dressings. Grade III—the presence of a full thickness ulcer, requiring surgical debridement, skin grafting, or a skin flap, under general anesthesia. The first ratings were completed following the familiarization meeting. The second rating was conducted 2 weeks later, with prior randomization of the scenario presentation order. Raters recorded their responses on a standard form and responses were then collated and transcribed onto an Excel spreadsheet. Each rating was identified by the rater’s profession and rating occasion, (eg, PTR1=physical therapist rating 1), but individuals were not identified. Statistical Analyses The data was analyzed with statistical support provided external to our institution. Fleiss’ κ statistics with 95% confidence intervals (CI) were used to determine the level of agreement (interrater reliability) between (Tables 2 and 3)All raters, across all MCD grades. Professional group across all MCD grades.

Statistical Analyses The data was analyzed with statistical support provided external to our institution. Fleiss’ κ statistics with 95% confidence intervals (CI) were used to determine the level of agreement (interrater reliability) between (Tables 2 and 3)All raters, across all MCD grades. Professional group across all MCD grades. TABLE 2 Fleiss’ κ for Interrater Reliability of the Modified Clavien-Dindo System for Children With Cerebral Palsy TABLE 3 Fleiss’ κ for Interrater Reliability Within Each Modified Clavien-Dindo System Grade Among All Raters Fleiss’ κ statistics with 95% CI were also used to describe the intrarater reliability for each rater (Table 4). The preference to use Fleiss’ κ over weighted κ were 2-fold: to eliminate the risk of falsely inflating our results, and to increase result reproducibility. TABLE 4 Fleiss’ κ for Intrarater Reliability of the Modified Clavien-Dindo System for Children With Cerebral Palsy A κ score of 0 to 0.2 was deemed as poor, 0.21 to 0.4 as fair, 0.41 to 0.6 as good, 0.61 to 0.8 as very good, and 0.81 to 1.0 as almost perfect agreement.12,13 All calculations were performed in Stata version 14.1 (StataCorp, College Station, TX).

TABLE 4 Fleiss’ κ for Intrarater Reliability of the Modified Clavien-Dindo System for Children With Cerebral Palsy A κ score of 0 to 0.2 was deemed as poor, 0.21 to 0.4 as fair, 0.41 to 0.6 as good, 0.61 to 0.8 as very good, and 0.81 to 1.0 as almost perfect agreement.12,13 All calculations were performed in Stata version 14.1 (StataCorp, College Station, TX). RESULTS Rating 1 Interrater Reliability The overall agreement for all raters on all MCD grades was very good (κ, 0.70; 95% CI, 0.61-0.80) (Table 2). The overall agreement varied among professional groups, ranging from κ 0.59 to 0.93. A difference in scores was noted between MCD I and II, compared with agreement among the other grades (Table 3). Overall agreement for MCD I and II was good (κ: 0.52, 0.47, respectively). Grading of MCD III, IV, and V AEs were near perfect (κ: 0.84, 0.97, 1.00, respectively). Rating 2 Interrater Reliability Reliability increased at rating 2, with very good overall agreement on MCD grades (κ, 0.75; 95% CI, 0.66-0.84) (Table 2). Grading of MCD I and II AEs slightly improved but remained good (κ: 0.57, 0.58, respectively) (Table 3). Grading of MCD III, IV, and V AEs were once again near perfect (κ: 0.90, 0.95, 1.00, respectively). Intrarater Reliability Overall intrarater reliability among raters was very good (average κ, 0.78). The highest level of agreement was seen among attending surgeons (κ, 0.80 to 1.00), orthopaedic clinical fellows (κ 0.71 to 0.90), and individuals with CP (κ, 0.61 to 0.93) (Table 4). The lowest level of agreement was observed among physical therapists (κ, 0.48 to 0.80).

ty among raters was very good (average κ, 0.78). The highest level of agreement was seen among attending surgeons (κ, 0.80 to 1.00), orthopaedic clinical fellows (κ 0.71 to 0.90), and individuals with CP (κ, 0.61 to 0.93) (Table 4). The lowest level of agreement was observed among physical therapists (κ, 0.48 to 0.80). DISCUSSION Preventing surgical AEs is critically important to providing high-quality clinical care, minimizing harm, maximizing function, and containing health care costs.8,14,15 Historically, surgeons have reported short-term complications and longer term treatment outcomes that do not involve patients’ perceptions16–19 and is hindered by a lack of standardization and reproducibility.20 A classification system that is valid, reliable, and easy to use may permit transparent standardized reporting of AEs, improve the accuracy of audits, and lead to more objective understanding and comparison of surgical outcome studies in the literature. Use of such systems can promote early recognition of events that deviate from the normal postoperative course, to prevent a cascade effect that could cause permanent morbidity or mortality. Clear documentation and collection of data related to complications will also add information on the associated risks of surgery, guiding the shared or informed decision-making process with parents, caregivers, and young people with CP.7,8

, to prevent a cascade effect that could cause permanent morbidity or mortality. Clear documentation and collection of data related to complications will also add information on the associated risks of surgery, guiding the shared or informed decision-making process with parents, caregivers, and young people with CP.7,8 This study shows a very good interrater and intrarater reliability of the MCD for lower limb surgery in children with CP. The system has good face validity and we have shown that it can be used reliably in a multidisciplinary team environment by surgeons, allied health and nursing professionals. Our data shows that a high level of agreement was consistent among orthopaedic attending surgeons and clinical fellows, which could reflect their experience and expertise in recognizing and managing AEs. Raters had lower agreement with MCD grades I and II overall, and this may indicate some uncertainty in distinguishing typical postoperative sequelae from minor AEs. Subtle differences exist between a treatment considered “preexisting” compared with the addition of new treatment. We think that agreement between MCD grades I and II could be improved by a priori discussion, and the development of more detailed guidelines are now included in Appendix 1 (Supplemental Digital Content 1, http://links.lww.com/BPO/A170). Near perfect agreement was achieved among MCD grades III, IV, and V, irrespective of professional background. This suggests that grading by treatments required to address the AE was clearly understood, and that the outcome worsened with increasing MCD grade.

Raters had lower agreement with MCD grades I and II overall, and this may indicate some uncertainty in distinguishing typical postoperative sequelae from minor AEs. Subtle differences exist between a treatment considered “preexisting” compared with the addition of new treatment. We think that agreement between MCD grades I and II could be improved by a priori discussion, and the development of more detailed guidelines are now included in Appendix 1 (Supplemental Digital Content 1, http://links.lww.com/BPO/A170). Near perfect agreement was achieved among MCD grades III, IV, and V, irrespective of professional background. This suggests that grading by treatments required to address the AE was clearly understood, and that the outcome worsened with increasing MCD grade. Children who are most in need of major reconstructive lower limb surgery21–23 are often the most medically frail.8,18 MCD grades I and II events occurred in up to 60% of children in a recent prospective cohort study of hip surgery in nonambulant children with CP.7 The most common complications were constipation, cast-related or splint-related skin irritation, inadequate pain and spasm control from malfunctioning epidural or morphine infusions, and respiratory infections. Most were self-limiting or resolved with simple medical treatment.7 However, some children had multiple AEs and in other children, minor AEs escalated to more serious events. For example, children functioning at Gross Motor Function Classification System V have a high prevalence of preexisting respiratory disease. Attempts to manage postoperative pain and spasm with narcotic infusions and diazepam can lead to respiratory depression and pneumonia, which may require an intensive care unit admission and mechanical ventilation.7,8 DiFazio et al8 reported similar findings, in which 65% of children with CP suffered from postoperative AEs at a rate nearly twice that of typically developing children. This contrasts with a 10.5% surgical and a 29.8% medical AE reported in a large, retrospective cohort study of 168 hip reconstructions involving 121 children with CP.22 Constipation and inadequate analgesia were not reported, which may be due to the retrospective nature of the study.22

of typically developing children. This contrasts with a 10.5% surgical and a 29.8% medical AE reported in a large, retrospective cohort study of 168 hip reconstructions involving 121 children with CP.22 Constipation and inadequate analgesia were not reported, which may be due to the retrospective nature of the study.22 The difference between the reported rates of AEs in outcome studies of children with CP suggests that underreporting of AEs exists in the literature. This is an important issue that requires addressing. Surgeons readily accept that wound infections, hardware failure, or nonunion are surgical AEs that should be reported.6,8 As physicians who operate, surgeons should also take responsibility for reporting, preventing, and ameliorating “medical” AEs. If the child was not subjected to general anesthesia and the operation, the exacerbation of constipation, pain, hypertonia, aspiration, and chest infection would not have occurred. Medical and surgical AEs should be “owned,” prevented, and managed by all members of the clinical team. This is the principal reason that we involved all members of our multidisciplinary team in assessing the reliability of the MCD for CP, as well as the perspective of individuals with CP. We strongly encourage a proactive system of prospective documentation, to improve the transparency of recognizing and reporting events.

is is the principal reason that we involved all members of our multidisciplinary team in assessing the reliability of the MCD for CP, as well as the perspective of individuals with CP. We strongly encourage a proactive system of prospective documentation, to improve the transparency of recognizing and reporting events. The key strengths of our study include the inclusion of participants from medical, nursing, and allied health professions, and of individuals with CP whom have experienced orthopaedic surgery. The diversity of our raters aimed to model holistic care provided by a multidisciplinary team, and included the perceptions of AEs in individuals with CP.

udy include the inclusion of participants from medical, nursing, and allied health professions, and of individuals with CP whom have experienced orthopaedic surgery. The diversity of our raters aimed to model holistic care provided by a multidisciplinary team, and included the perceptions of AEs in individuals with CP. This study is the first to examine the reliability of the MCD in children with CP, and it has some limitations. First, raters were inexperienced in using the MCD, resulting in less than perfect agreement. Second, this study highlights the difficulty of distinguishing the severity of minor AEs (MCD I and II), with little comparative data in existing literature. With increasing utilization of this system in time, it is felt that reliability in grading minor AEs will also continue to improve, shown by the increased observed agreement from rating 1 to rating 2. Future reporting of all minor AEs should be encouraged in the literature to characterize the true frequency of events, identify risk factors and develop strategies for prevention in the postoperative period. Third, many of our complex care children experience more than 1 AE. The MCD system currently has no guidance on how to rate or summarize the effects of multiple complications.

iterature to characterize the true frequency of events, identify risk factors and develop strategies for prevention in the postoperative period. Third, many of our complex care children experience more than 1 AE. The MCD system currently has no guidance on how to rate or summarize the effects of multiple complications. In conclusion, this study has shown that the MCD is a system that can be utilized reliably for grading AEs in CP, following hip and lower limb surgery. The MCD is a useful tool that is easily understood and can be explained to any member of the multidisciplinary team. Future research will be directed on developing a system for grading multiple AEs and testing the validity of the MCD in lower limb surgery for CP in a real time, prospective clinical trial. We recommend the use of the MCD until there is consensus for a gold standard system in AE reporting. Supplementary Material SUPPLEMENTARY MATERIAL Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.pedorthopaedics.com. None of the authors received financial support and ethical approval was not required for this study. H.K.G. is a member of the OrthoPediatrics Surgeons Advisory Board. H.K.G. and K.W. are supported by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Cerebral Palsy (CRE-CP). The remaining authors declare no conflicts of interest.

Spinal muscular atrophy (SMA; MIM# 253300) is a common monogenic cause of spinal motor neuron (SMN) degeneration caused by biallelic deletions of SMN1, which encodes SMN protein.1–4 Within the SMN1 locus on chromosome 5q13, humans have a second SMN-encoding gene (SMN2) that can be present in multiple copies. SMN2 contains a base difference (c.850C>T) that excludes exon 7 from ~90% of mRNA transcripts to produce an unstable protein fragment (SMN∆7) that is rapidly degraded.5,6 Residual intact SMN translated from each SMN2 copy partially compensates for SMN1 deficiency such that genomic SMN2 copy number correlates inversely with disease timing and severity.7–9 Functional overlap between SMN1 and SMN2 inspired the design of nusinersen, an antisense oligonucleotide engineered to alter splicing of SMN2 pre-mRNA and thereby increase expression of stable SMN protein.10 Repeated intrathecal injections of nusinersen improve survival and motor development among infants with severe SMA (2 copies of SMN2) treated between 30 and 262 days of age, and also benefit patients started on therapy between 2 and 9 years of age as observed in CHERISH, a study to assess the efficacy and safety of nusinersen in participants with later-onset SMA (NCT02292537).11

l and motor development among infants with severe SMA (2 copies of SMN2) treated between 30 and 262 days of age, and also benefit patients started on therapy between 2 and 9 years of age as observed in CHERISH, a study to assess the efficacy and safety of nusinersen in participants with later-onset SMA (NCT02292537).11 The CHERISH trial excluded older symptomatic patients with joint contractures, severe scoliosis (radiographic Cobb angle >40 degrees), gastrostomy, or dependence on mechanical ventilatory support.11 Unfortunately, such complications are common among surviving SMA patients, many of whom have skeletal deformity or instrumentation that hinders repeated interlaminar nusinersen dosing.12,13 This has prompted a search for alternative nusinersen dosing strategies14 and engenders related questions about how to structure functional assessments for patients who have advanced neuromuscular disability and its attendant skeletal and respiratory complications.12,13,15–17 We were confronted with this problem in March 2017, when an 11-year-old Mennonite boy with advanced SMA was denied intrathecal nusinersen at 2 different academic medical centers because of spinal fusion.

ents who have advanced neuromuscular disability and its attendant skeletal and respiratory complications.12,13,15–17 We were confronted with this problem in March 2017, when an 11-year-old Mennonite boy with advanced SMA was denied intrathecal nusinersen at 2 different academic medical centers because of spinal fusion. To circumvent spinal pathology, we devised a novel subcutaneous intrathecal catheter (SIC) system using an off-label configuration of 2 Food and Drug Administration (FDA)-approved devices: an intrathecal catheter and power injectable implantable infusion port. This allowed for repeated nusinersen dosing via subcutaneous port (Fig. 1). Following successful implantation in the sentinel patient, we designed a prospective study to evaluate 20 SMA participants treated via SIC for 14 months (through 4 loading and 3 maintenance doses of nusinersen) and tailored functional assessments to older individuals with moderate to severe neuromuscular disease.11,18 Here we report preliminary safety and tolerability of the SIC for the first 10 participants, each of whom received 3 loading doses over 4 weeks, and discuss the implications for future studies.

es of nusinersen) and tailored functional assessments to older individuals with moderate to severe neuromuscular disease.11,18 Here we report preliminary safety and tolerability of the SIC for the first 10 participants, each of whom received 3 loading doses over 4 weeks, and discuss the implications for future studies. FIGURE 1 SIC system. A, The interlocked intrathecal catheter and subcutaneous infusion port used to construct the hybrid nusinersen delivery system. B, Distortions of spinal and pulmonary anatomy, commonly observed among older SMA patients, that inspired design of the SIC system. C, The SIC system in situ, with the infusion port and intrathecal catheter tip marked by a yellow arrow and arrowhead, respectively. D, The SIC allows for safe, low-cost, repeated outpatient nusinersen dosing. SIC indicates subcutaneous intrathecal catheter; SMA, spinal muscular atrophy.

pired design of the SIC system. C, The SIC system in situ, with the infusion port and intrathecal catheter tip marked by a yellow arrow and arrowhead, respectively. D, The SIC allows for safe, low-cost, repeated outpatient nusinersen dosing. SIC indicates subcutaneous intrathecal catheter; SMA, spinal muscular atrophy. METHODS Patients Ten study participants born between 1987 and 2012 shared homozygous exon 7 deletions of SMN1 that traced to common ancestral founders across 11 generations and segregated into individuals with 2 (n=1), 3 (n=8), or 4 (n=1) copies of SMN2 (Table 1). The 6 eldest patients (age, 12.1 to 30.5 y) had spinal fusion that precluded repeated lumbar puncture; the 4 youngest (age, 5.4 to 10.4 y) had no spinal pathology, but parents elected the SIC based on its perceived administration safety, convenience, and cost. The study was approved by Penn Medicine-Lancaster General Hospital Institutional Review Board. Adults consented in writing to participate and parents consented on behalf of their children. In accordance with journal policy, a separate signed consent was obtained for reproduction of the photograph in Figure 1. This interim analysis, focused upon initial safety and tolerability of the SIC, was conducted between June 2017 and January 2018. TABLE 1 Patient Characteristics (n=10), Comorbidities, and Cerebrospinal Fluid Indices

METHODS Patients Ten study participants born between 1987 and 2012 shared homozygous exon 7 deletions of SMN1 that traced to common ancestral founders across 11 generations and segregated into individuals with 2 (n=1), 3 (n=8), or 4 (n=1) copies of SMN2 (Table 1). The 6 eldest patients (age, 12.1 to 30.5 y) had spinal fusion that precluded repeated lumbar puncture; the 4 youngest (age, 5.4 to 10.4 y) had no spinal pathology, but parents elected the SIC based on its perceived administration safety, convenience, and cost. The study was approved by Penn Medicine-Lancaster General Hospital Institutional Review Board. Adults consented in writing to participate and parents consented on behalf of their children. In accordance with journal policy, a separate signed consent was obtained for reproduction of the photograph in Figure 1. This interim analysis, focused upon initial safety and tolerability of the SIC, was conducted between June 2017 and January 2018. TABLE 1 Patient Characteristics (n=10), Comorbidities, and Cerebrospinal Fluid Indices Surgical Procedure and Nusinersen Dosing We constructed a hybrid infusion system using 2 FDA-approved devices: a catheter commonly utilized for continuous or repeated intrathecal infusion (Medtronic) and a power injectable implantable infusion port (MedComp) designed for repetitive blood sampling or chemotherapy (Fig. 1). The infusion port locked firmly into the intrathecal catheter, nonleakage was verified ex vivo, and the implantation procedure was performed under general anesthesia.

rathecal infusion (Medtronic) and a power injectable implantable infusion port (MedComp) designed for repetitive blood sampling or chemotherapy (Fig. 1). The infusion port locked firmly into the intrathecal catheter, nonleakage was verified ex vivo, and the implantation procedure was performed under general anesthesia. We exposed the spine through a 3 to 4 cm incision and drilled a hole (under fluoroscopic guidance) through the spinal fusion to access the epidural space. The catheter was threaded into the midthoracic intrathecal space and the threading needle withdrawn to document free backflow of cerebrospinal fluid (CSF). Although nusinersen is typically administered in the lumbar region via interlaminar puncture, SMA affects lower motor neurons along the entire neuraxis, and lumbar administration is based on tactical rather than biological considerations.19 Unlike infants with SMA who spend much of their time supine,18 most of our patients are upright (ie, on a wheelchair) during waking hours. We therefore chose a higher delivery site to expose thoracic and potentially cervical motor neurons to nusinersen.

tion is based on tactical rather than biological considerations.19 Unlike infants with SMA who spend much of their time supine,18 most of our patients are upright (ie, on a wheelchair) during waking hours. We therefore chose a higher delivery site to expose thoracic and potentially cervical motor neurons to nusinersen. Once positioned, an anchor was placed over the catheter and sutured to deep fascia, just a top bone. The infusion port was then placed through a 2 cm incision of the chest wall and implanted subcutaneously, where it was anchored to hard fascia of the chest, flank, or lower back, depending on anatomic considerations and patient preference. The port catheter was tunneled under the fascia to the posterior wound and connected firmly to the intrathecal catheter. Before wound closure, the port was accessed to document CSF flow through the complete hybrid system. The posterior bone hole was closed with a pressure injection of surgical sealant-coagulant to prevent CSF leak and fascia were closed tightly to further safeguard against leakage. Following complete posterior wound closure, the exposed anterior infusion port was again aspirated to document free flow. A CSF volume of 5 mL was withdrawn from the port followed by injection of 12 mg (5 mL) of nusinersen (loading dose 1; LD1), which was then cleared from the catheter using 0.5 mL of normal saline. The anterior wound was then completely closed.

the exposed anterior infusion port was again aspirated to document free flow. A CSF volume of 5 mL was withdrawn from the port followed by injection of 12 mg (5 mL) of nusinersen (loading dose 1; LD1), which was then cleared from the catheter using 0.5 mL of normal saline. The anterior wound was then completely closed. Patients remained supine for 48 hours postoperatively, after which they were placed in seated position and, if asymptomatic when upright for 12 hours, discharged home. Surgical wound inspection was performed on postoperative day 14 to insure the access port was completely under the skin, readily palpable, and easily accessed via a noncoring needle (Fig. 1). No imaging, sedation, or regional anesthesia was required to access the port or administer drug thereafter. All subsequent nusinersen doses were given in the outpatient setting by standard procedure: (1) topical lidocaine 2.5%/prilocaine 2.5% was applied over the infusion port at least 30 minutes before dosing; (2) skin overlying the access port was then prepped and draped using sterile technique (Fig. 1); (3) the port reservoir was accessed via noncoring needle and flushed with 0.2 mL saline to float the intrathecal catheter tip free from surrounding pia and arachnoid mater; (4) 3 mL CSF was withdrawn and discarded and an additional 4 mL withdrawn for analysis; and (5) nusinersen 12 mg (5 mL) was infused through the port and the catheter was flushed with 2 mL saline.

g needle and flushed with 0.2 mL saline to float the intrathecal catheter tip free from surrounding pia and arachnoid mater; (4) 3 mL CSF was withdrawn and discarded and an additional 4 mL withdrawn for analysis; and (5) nusinersen 12 mg (5 mL) was infused through the port and the catheter was flushed with 2 mL saline. Assessments Each participant received 3 loading doses of nusinersen via SIC (baseline, LD1; week 2, LD2; week 4, LD3). At scheduled doses, we obtained laboratory indices of safety and solicited information about adverse events and concomitant medications. Before administration of LD3, CSF was collected through the SIC and divided into aliquots for measurement of cell counts, protein, and glucose. A structured battery of assessments was conducted at the preimplantation visit and 4 weeks after implantation, before administration of LD3. We did not expect to observe any significant changes in motor function, power, or respiratory performance after just 2 doses of nusinersen, which for infants only improves event-free survival beyond the loading phase.18

conducted at the preimplantation visit and 4 weeks after implantation, before administration of LD3. We did not expect to observe any significant changes in motor function, power, or respiratory performance after just 2 doses of nusinersen, which for infants only improves event-free survival beyond the loading phase.18 Motor assessments were performed at ~09:00 hours by the same examiner and included tests of neuromuscular function [Revised Hammersmith Scale (RHS)20 or Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders,21 as appropriate to pretreatment functional level]. Nine (90%) participants could be studied using the RHS, for which scores range between 0 and 66 (with higher numbers indicating better motor function). Motor speed and dexterity were assessed using the National Institutes of Health (NIH) Toolbox pegboard,22 and power was measured by 12 dynamometry maneuvers (JTech Medical, Commander Echo MMT Dynamometry). A novel dynamometric parameter, the SMA Force Index (SFI) was devised to capture the distribution of weakness characteristic of SMA (see Supplemental Materials for details, Supplemental Digital Content 1, http://links.lww.com/BPO/A180).

asured by 12 dynamometry maneuvers (JTech Medical, Commander Echo MMT Dynamometry). A novel dynamometric parameter, the SMA Force Index (SFI) was devised to capture the distribution of weakness characteristic of SMA (see Supplemental Materials for details, Supplemental Digital Content 1, http://links.lww.com/BPO/A180). Baseline compound muscle action potential (CMAP; mV) was recorded from the distribution of ulnar (abductor digiti minimus), radial (extensor carpi radialis longus), and deep peroneal (extensor digitorum brevis, tibialis anterior) nerves—and used to calculate an average CMAP amplitude for each patient.23 Pulmonary function testing was performed in the seated position in accordance with American Thoracic Society standards using an EasyOne Pro Lab (NDD). Maximal inspiratory (MIP) and expiratory (MEP) pressures were measured after full exhalation and inhalation, respectively, using a Micro respiratory pressure monitor (RPM; Micro Direct); these are reported as z-scores calculated from age-specific and sex-specific reference values,24 where z=(patient value/reference mean)/(reference SD) and normal z-scores range between −2 and +2. To assess well-being, we administered age-appropriate Pediatric Quality of Life (PedsQL) Acute and Family Impact Modules (www.pedsql.org; parent and child forms)25 and the NIH Toolbox Emotion Domain.22

reference values,24 where z=(patient value/reference mean)/(reference SD) and normal z-scores range between −2 and +2. To assess well-being, we administered age-appropriate Pediatric Quality of Life (PedsQL) Acute and Family Impact Modules (www.pedsql.org; parent and child forms)25 and the NIH Toolbox Emotion Domain.22 Statistics Functional measures, laboratory indices, and measures of HRQOL at preimplantation and week 4 were compared using a paired t test. Relationships of RHS, dynamometer measures, and pulmonary function to patient age were studied with Pearson (r) correlations (Prism 7, GraphPad). RESULTS Baseline Assessments Motor function, dexterity, power, mean CMAP, pulmonary function, and HRQOL among 10 study participants are represented in Tables 1 and 2. For 8 patients with 3 copies of SMN2, the RHS, weigt-adjusted SFI, and select dynamometry maneuvers correlated inversely with age in children below 16 years (Pearson r values −0.94 to −0.97). These correlations broke down thereafter, revealing their limits for patients with advanced neuromuscular disease (Fig. 2). Measured parameters did not change significantly after 2 loading doses of nusinersen (Table 2). Baseline mean CMAP varied by SMN2 copy number: values for patients with 4 (n=1), 3 (n=8), and 2 (n=1) copies of SMN2 were 6.6±0.8, 1.3±0.7, and 0.2±0.1 mV, respectively. Motor nerve amplitude did not vary as a function of age among patients with 3 copies of SMN2 (Fig. 2). TABLE 2 Clinical Assessments Pretreatment and After 2 Loading Doses of Nusinersen (n=10)

RESULTS Baseline Assessments Motor function, dexterity, power, mean CMAP, pulmonary function, and HRQOL among 10 study participants are represented in Tables 1 and 2. For 8 patients with 3 copies of SMN2, the RHS, weigt-adjusted SFI, and select dynamometry maneuvers correlated inversely with age in children below 16 years (Pearson r values −0.94 to −0.97). These correlations broke down thereafter, revealing their limits for patients with advanced neuromuscular disease (Fig. 2). Measured parameters did not change significantly after 2 loading doses of nusinersen (Table 2). Baseline mean CMAP varied by SMN2 copy number: values for patients with 4 (n=1), 3 (n=8), and 2 (n=1) copies of SMN2 were 6.6±0.8, 1.3±0.7, and 0.2±0.1 mV, respectively. Motor nerve amplitude did not vary as a function of age among patients with 3 copies of SMN2 (Fig. 2). TABLE 2 Clinical Assessments Pretreatment and After 2 Loading Doses of Nusinersen (n=10) FIGURE 2 Multidomain baseline assessments. Among SMA patients with 3 copies of SMN2 and below 16 years of age (blue circles), we found strong inverse Pearson correlations between age and Revised Hammersmith Functional Motor Scale (A), weight-adjusted SFI (B), and forced vital capacity. This association broke down after age 16 (gray circles). C, MEP as compared with inspiratory pressure (corrected for age and sex) was low for all patients, reflecting weakness of intercostal muscles relative to the diaphragm. Gray shaded area indicates normal z-scores ranging from −2 to +2. D, Baseline mean CMAP, averaged from 4 separate recordings, varied by SMN2 copy number (white triangle, 4 copies; blue circles, 3 copies; purple diamond, 2 copies) but did not vary as a function of age among patients with 3 SMN2 copies. Gray shaded area represents the range of CMAP amplitude observed in ambulatory (as compared with nonambulatory) SMA patients (Lewelt et al23). E, Independent PedsQL responses of participants and their caregivers were generally in good agreement (blue-dashed line represents unity) but there was a tendency for parents to overrate their child’s well-being. F, The overall burden of disease on family functioning (PedsQL family impact module) was strongly associated with patient age. CMAP indicates compound muscle action potential; SMA, spinal muscular atrophy; PedsQL, Pediatric Quality of Life.

ity) but there was a tendency for parents to overrate their child’s well-being. F, The overall burden of disease on family functioning (PedsQL family impact module) was strongly associated with patient age. CMAP indicates compound muscle action potential; SMA, spinal muscular atrophy; PedsQL, Pediatric Quality of Life. Total lung capacity and forced vital capacity were 32% to 78% and 16% to 97% predicted, respectively (Tables 1, 2, and Fig. 2). MIP and MEP pressures decreased with age and MEPs corrected for age and sex were low relative to MIPs (Fig. 2). This reflects a reversal of normal physiology characteristic of SMA; the diaphragm is less impaired than intercostal muscles and results in development of a bell-shaped chest (Fig. 1). PedsQL responses of participants and their caregivers, elicited independently, were generally in good agreement (r2=0.77, P<0.0001). Participants and parents alike consistently rated physical function lower than emotional function and parents tended to overrate their child’s physical well-being (Fig. 2). Within our cohort of predominantly Old Order Mennonite participants harboring 3 copies of SMN2, baseline indices of emotional health were similar to values from healthy pediatric reference populations, 26,27 whereas physical functioning scores were 60% to 70% lower (Table 2).

their child’s physical well-being (Fig. 2). Within our cohort of predominantly Old Order Mennonite participants harboring 3 copies of SMN2, baseline indices of emotional health were similar to values from healthy pediatric reference populations, 26,27 whereas physical functioning scores were 60% to 70% lower (Table 2). Safety and Tolerability of the SIC For all 10 participants, the SIC was successfully implanted during a single procedure lasting an average 1.4 (range, 1.1 to 2.0) hours followed by a hospital stay of 50 to 55 hours. There were no perioperative or postoperative complications and all wounds were clean and dry by postoperative week 2. Each participant received 3 nusinersen doses over a 4 week postimplantation period (30 doses for the cohort). All outpatient nusinersen doses were successfully administered via SIC with a single attempt through topical anesthetic, and required no regional or systemic analgesia, cognitive distraction, ultrasound guidance, respiratory precautions, or sedation.28 No patient required oropharyngeal suctioning, supplemental oxygen, or noninvasive ventilation before or during receipt of an outpatient SIC dose.

single attempt through topical anesthetic, and required no regional or systemic analgesia, cognitive distraction, ultrasound guidance, respiratory precautions, or sedation.28 No patient required oropharyngeal suctioning, supplemental oxygen, or noninvasive ventilation before or during receipt of an outpatient SIC dose. During the interim study period, 3 adverse events occurred among 3 participants. These included: (1) urinary tract infection in a male child, (2) back pain secondary to a protruding spinal rod in an adult female, and (3) inability to withdraw CSF from the SIC port during LD2 in another adult female; nusinersen could, however, be freely administered through this same port, implicating dynamic suction-induced catheter obstruction. None of these events were serious and only the latter was definitely related to the device. Nine study participants had CSF withdrawn from the SIC. CSF glucose (median, 53 mg/dL; range, 49 to 76 mg/dL) and protein (median, 25 mg/dL; range, 18 to 68 mg/dL) levels were normal. White blood cells were slightly elevated in 2 (22%) of 9 specimens (median, 1 cell/µL; range, 0 to 12 cells/µL) and red blood cells were detected in 7 (78%) of 9 specimens (median, 4; range, 0 to 2930 cells/µL) (Table 1). There were no serum or urine laboratory abnormalities associated with SIC nusinersen administration.

ite blood cells were slightly elevated in 2 (22%) of 9 specimens (median, 1 cell/µL; range, 0 to 12 cells/µL) and red blood cells were detected in 7 (78%) of 9 specimens (median, 4; range, 0 to 2930 cells/µL) (Table 1). There were no serum or urine laboratory abnormalities associated with SIC nusinersen administration. DISCUSSION Barriers to Nusinersen Administration Nusinersen has well-documented efficacy for infants and children with SMA,11,18 but clinical studies to date do not adequately address older patients who have more advanced neuromuscular disease and its attendant skeletal and pulmonary morbidities. Specifically, scoliosis is observed in as many as 80% of SMA patients with 2 or 3 copies of SMN2 who survive into late childhood12 and can preclude safe, repeated interlaminar dosing of nusinersen. These same patients often require sustained mechanical ventilatory support or gastrostomy tube feeding, which were exclusion criteria for CHERISH.11

observed in as many as 80% of SMA patients with 2 or 3 copies of SMN2 who survive into late childhood12 and can preclude safe, repeated interlaminar dosing of nusinersen. These same patients often require sustained mechanical ventilatory support or gastrostomy tube feeding, which were exclusion criteria for CHERISH.11 Absolute anatomic and relative pulmonary barriers to repeated interlaminar dosing have prompted efforts to administer nusinersen by alternative routes. As one recent example, 4 SMA patients with spinal fusion received 15 consecutive nusinersen injections via a transforaminal route guided by cone-beam computed tomography with fluoroscopic navigational overlay.14 Although the complication rate was low (6.7%), each procedure was technically complex, required sedation, and incurred radiation exposure. Lower complication rates from lumbar puncture (ie, 6% to 17%) might be achieved with conscious sedation16,29 but consistently safe, controlled interlaminar access in young people often requires a high degree of technical expertise and/or general anesthesia.29–31

plex, required sedation, and incurred radiation exposure. Lower complication rates from lumbar puncture (ie, 6% to 17%) might be achieved with conscious sedation16,29 but consistently safe, controlled interlaminar access in young people often requires a high degree of technical expertise and/or general anesthesia.29–31 Even among SMA patients without advanced neuromuscular disease or spinal pathology, repeated interlaminar dosing of nusinersen poses challenges. The overall incidence of traumatic lumbar puncture in children ranges from 20% to 50% and is highest among newborns.32–34 In one series of 73 lumbar punctures for 28 SMA patients (2 to 14 y), headache, back pain, or CSF leak complicated 32% of nusinersen doses.35 In a second series of 84 interlaminar nusinersen doses at an academic neuromuscular center (20 patients, ages 2 to 50 mo),28 the first lumbar puncture attempt failed 33% of the time (mean, 1.5±1.0 attempts/child/dose) and 2 (10%) children below 6 months of age required ultrasound guidance. Oropharyngeal suctioning was regularly performed, and 7 (35%) children received noninvasive ventilation during lumbar puncture. Procedural sedation and postprocedural analgesia were required for 30% and 40% of children, respectively.28

child/dose) and 2 (10%) children below 6 months of age required ultrasound guidance. Oropharyngeal suctioning was regularly performed, and 7 (35%) children received noninvasive ventilation during lumbar puncture. Procedural sedation and postprocedural analgesia were required for 30% and 40% of children, respectively.28 Preliminary Device Safety and Tolerability In contrast to repeated lumbar puncture, dosing via SIC required only topical anesthetic and took <20 minutes during the course of routine outpatient visit. All doses were administered on the first attempt and patients experienced no significant pain, distress, or clinical instability from the procedure. Accordingly, we found no need to use special respiratory maneuvers, systemic analgesia, conscious sedation, or cognitive distraction. Parents of the four youngest study participants who had no anatomic or pulmonary contraindications to interlaminar dosing—elected SIC implantation as potentially safer, more convenient, and less costly than repeated lumbar puncture.

espiratory maneuvers, systemic analgesia, conscious sedation, or cognitive distraction. Parents of the four youngest study participants who had no anatomic or pulmonary contraindications to interlaminar dosing—elected SIC implantation as potentially safer, more convenient, and less costly than repeated lumbar puncture. Efficacy was not an endpoint of the present study. However, consistent with best clinical practice, we used a multidimensional battery to assess patients at pretreatment baseline and at various intervals until study completion (ie 14 mo, after 4 loading and 3 maintenance doses of nusinersen). We expect therapeutic effects of nusinersen in this cohort will be relatively modest, slow to emerge, and observed primarily as an arrest of disease progression.11 Unfortunately, as shown in Figure 2, many conventional endpoints of motor function used for infants and young children lose their informative value after age 16 years. Thus, different assessment tools might be needed to gauge efficacy of disease-modifying therapies in adolescents and adults with SMA.

ase progression.11 Unfortunately, as shown in Figure 2, many conventional endpoints of motor function used for infants and young children lose their informative value after age 16 years. Thus, different assessment tools might be needed to gauge efficacy of disease-modifying therapies in adolescents and adults with SMA. Laboratory monitoring supported the safety of the SIC but, on a cautionary note, we detected red blood cells (median, 4; range, 0 to 2930 cells/µL) in 7 (78%) of 9 specimens withdrawn from the system (Table 1). A similar phenomenon was observed among newborns with an intrathecal reservoir or ventriculoperitoneal shunt,36 raising the possibility that indwelling CSF catheter tips, when not continuously infusing, can adhere to pial or arachnoid membranes to become dynamically obstructed and/or cause microvascular injury when suction is applied. To safeguard against this, we added an initial 0.2 mL saline flush to the administration protocol to gently dislodge the catheter tip from surrounding thecal membranes before withdrawal of CSF. It is worth noting that CSF withdrawal and examination were a means by which to assess SIC patency and safety for the purpose of this trial, but need not be a routine component of long-term administration protocols.

protocol to gently dislodge the catheter tip from surrounding thecal membranes before withdrawal of CSF. It is worth noting that CSF withdrawal and examination were a means by which to assess SIC patency and safety for the purpose of this trial, but need not be a routine component of long-term administration protocols. Clinical and Economic Implications Since the FDA approved nusinersen for treatment of all forms of SMA in December 2016, there is growing demand for delivery methods adapted to older patients with respiratory and spinal comorbidities. The publication of CHERISH,11 which demonstrated clinical efficacy in an older SMA patient population with later-onset disease, brought the need into sharp relief. In recognition of this fact and its time-sensitivity for many patients with SMA, we chose a relatively short interval to describe device implantation and preliminary safety with the intention to prompt additional research in this area. If the SIC or similar device proves safe and well tolerated in multicenter trials involving more patients over longer intervals, indwelling catheter systems might become a preferred route of nusinersen dosing for patients across the SMA spectrum. This could not only increase the proportion of patients who receive drug, but also reduce its overall administration cost (Fig. 3).

d in multicenter trials involving more patients over longer intervals, indwelling catheter systems might become a preferred route of nusinersen dosing for patients across the SMA spectrum. This could not only increase the proportion of patients who receive drug, but also reduce its overall administration cost (Fig. 3). FIGURE 3 Administration economics. Projected nusinersen administration costs (not including drug) for 10 participants were plotted over 10 years, assuming a 1-time SIC implantation cost of $22,000 and an annual medical inflation rate of 6%. The SIC (blue line) yields average savings of $24,000 per child per year (2.4 million dollars for the cohort over 10 y) as compared with repeated lumbar puncture (gray shaded area, bounded by upper and lower limits of projected interlaminar administration costs). SIC indicates subcutaneous intrathecal catheter.

of 6%. The SIC (blue line) yields average savings of $24,000 per child per year (2.4 million dollars for the cohort over 10 y) as compared with repeated lumbar puncture (gray shaded area, bounded by upper and lower limits of projected interlaminar administration costs). SIC indicates subcutaneous intrathecal catheter. In our office, nusinersen via SIC cost US$75 per administration. By comparison, 4 Mennonite children (age, 0.7 to 2.9 y) treated contemporaneously by standard lumbar puncture incurred hospital charges of $5000 and $9000 per administration, depending on the type and duration of sedation used. On the basis of these data, Figure 3 depicts comparative administration costs (not including drug) for 10 participants over a period of 10 years, assuming an SIC implantation cost of $22,000 and an annual medical inflation rate of 6%. The SIC yields average savings of $24,000 per child per year (2.4 million dollars for the cohort over 10 y). Although not a primary endpoint of this study, this simple economic heuristic has unambiguous implications for the overall cost of nusinersen administration worldwide.

and an annual medical inflation rate of 6%. The SIC yields average savings of $24,000 per child per year (2.4 million dollars for the cohort over 10 y). Although not a primary endpoint of this study, this simple economic heuristic has unambiguous implications for the overall cost of nusinersen administration worldwide. CONCLUSIONS AND FUTURE DIRECTIONS In summary, nusinersen via repeated intrathecal injection is effective therapy for all types of SMA,11,18 but its standard method of interlaminar delivery poses both absolute and relative challenges for a large proportion of patients. More data are needed to determine if nusinersen has comparable efficacy when delivered by subcutaneous port as compared with the standard interlaminar route. However, our initial observations are promising, and long-term administration of nusinersen via the SIC or similar device has the potential to double the number of children worldwide who can safely receive the drug12,14 while simultaneously lowering its long-term administration cost 5- to 10-fold. Although the SIC was designed for SMA patients with advanced disease and attendant spinal pathology, our preliminary observations have implications for younger, less severely affected patients. As private and government insurers adapt to the extraordinary costs associated with new disease-modifying precision therapies, they will likely seek practical innovations like the SIC, which have the potential to safely control administration costs while preserving therapeutic value.

r, less severely affected patients. As private and government insurers adapt to the extraordinary costs associated with new disease-modifying precision therapies, they will likely seek practical innovations like the SIC, which have the potential to safely control administration costs while preserving therapeutic value. Supplementary Material SUPPLEMENTARY MATERIAL Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.pedorthopaedics.com. ACKNOWLEDGMENTS This work was supported in part by charitable contributions from the communities we serve. We thank SMA patients and their families for their creativity, courage, and partnership in this endeavor. This study was funded in part by a grant from Biogen, the manufacturer of nusinersen. The authors received no direct or indirect compensation from Biogen and have no personal financial interests in the company. Author Robert M. Reed reports grants from Flight Attendants Medical Research Institute (FAMRI) during the conduct of the study. Funding from FAMRI did not influence the collection or analysis of data. The authors declare no conflicts of interest.

Developmental dysplasia of the hip (DDH) is the most common pediatric hip condition, affecting 4 to 7/1000 live births, but the true prevalence is difficult to accurately quantify. Severity ranges from mild instability in a reduced hip to complete hip dislocation. The Pavlik harness is one of the most commonly used orthoses for the nonoperative management of DDH, with success rates of 95% to 100% reported for management of hip instability.1,2 However, infants with hips dislocated at rest continue to have the poorest prognosis, regardless of management.3–7 In these cases, the dislocated hip can either be reducible or irreducible during a clinical examination. Those hips that are irreducible present particular challenges to treatment, with harness treatment failure rates reported in 37% to 100% of patients.3–7 Harness failure typically necessitates surgical intervention in the form of closed or open reduction in order to achieve concentric reduction of the hip.

examination. Those hips that are irreducible present particular challenges to treatment, with harness treatment failure rates reported in 37% to 100% of patients.3–7 Harness failure typically necessitates surgical intervention in the form of closed or open reduction in order to achieve concentric reduction of the hip. The variability in incidence, diagnosis, and treatment outcomes of DDH reported in the literature highlights the lack of standardized screening and management protocols and emphasizes the need for stronger supporting evidence. Some of this variability arises due to the broad spectrum of DDH pathology. Most previous studies are single center, retrospective and have no radiologic confirmation of hip position. To address this knowledge gap, we established a multicentre prospective observational study of children who have been diagnosed with hips dislocated at rest. This study excludes all teratological hips, whereby dislocation is secondary to other causes (neuromuscular, syndromic, chromosomal abnormalities, sacral agenesis, myelodysplasia, arthrogyposis). Therefore, all hips in this study are primarily dislocated and fall within the true definition of DDH. The purpose of this study was to examine variations in treatment modalities for infants diagnosed below 6 months of age with dislocated irreducible (D/I) hips at rest. This study aimed to identify variables associated with increased risk of treatment failure for this particularly challenging patient cohort.

The variability in incidence, diagnosis, and treatment outcomes of DDH reported in the literature highlights the lack of standardized screening and management protocols and emphasizes the need for stronger supporting evidence. Some of this variability arises due to the broad spectrum of DDH pathology. Most previous studies are single center, retrospective and have no radiologic confirmation of hip position. To address this knowledge gap, we established a multicentre prospective observational study of children who have been diagnosed with hips dislocated at rest. This study excludes all teratological hips, whereby dislocation is secondary to other causes (neuromuscular, syndromic, chromosomal abnormalities, sacral agenesis, myelodysplasia, arthrogyposis). Therefore, all hips in this study are primarily dislocated and fall within the true definition of DDH. The purpose of this study was to examine variations in treatment modalities for infants diagnosed below 6 months of age with dislocated irreducible (D/I) hips at rest. This study aimed to identify variables associated with increased risk of treatment failure for this particularly challenging patient cohort. METHODS The multicenter hip dysplasia database prospectively enrolled consented infants with dislocated hips at rest from 7 centers across North America, Europe, and Australia with Ethics Board Approval from each participating institution.7 All hips were Ortolani negative on clinical examination. Only those that had radiologic confirmation of D/I status were included. This required an USS demonstrating a dislocated femoral head at rest with failure of enlocation on dynamic testing, or a plain radiograph with the hip in a high dislocated position (IHDI grade III/IV8). As this is a prospective observational study, all assessments were carried out in accordance with individual surgeon/center protocol. Consequently the sonographic examination was performed by the pediatric orthopaedic surgeon at some centers and by the pediatric radiologist at others. All practitioners have DDH as a subspeciality of their practice, thus the level is “expert.” All hips with a neuromuscular or syndromic cause for the dislocation (ie, a teratological hip) do not fall within the definition of true DDH, and were therefore excluded. This included excessively premature infants. This study focused on the cohort of patients below 6 months of age with the most severely affected hips—dislocated but irreducible. The database was analyzed from its inception in August 2010 to April 2016 for all D/I hips. Baseline data, treatment strategies, outcomes, and complications were compared. Only patients with at least 20 months of follow-up were included in analysis, as per initial study criteria of 2 year follow-up ±4 months.

educible. The database was analyzed from its inception in August 2010 to April 2016 for all D/I hips. Baseline data, treatment strategies, outcomes, and complications were compared. Only patients with at least 20 months of follow-up were included in analysis, as per initial study criteria of 2 year follow-up ±4 months. Primary outcome was successful reduction, defined as a reduction obtained while in Pavlik harness and maintained after removal, with no requirement for further intervention in the follow-up period. Failure of Pavlik treatment was deemed as abandonment of the harness before achieving a concentric reduction for any reason. Outcomes depending on age at diagnosis, hip laterality, sex, type of treatment, and contralateral hip status were explored. Statistical analysis was performed using Excel and Graphpad Prism v6 with significance defined as P<0.05. Continuous variables were compared with unpaired t test and categorical variables were compared by χ2 test. Patients treated by an alternate method were analyzed descriptively.

ntralateral hip status were explored. Statistical analysis was performed using Excel and Graphpad Prism v6 with significance defined as P<0.05. Continuous variables were compared with unpaired t test and categorical variables were compared by χ2 test. Patients treated by an alternate method were analyzed descriptively. RESULTS Patient Inclusions At review, 412 hips in 327 infants diagnosed below 6 months of age were included in the database with potential for at least 20 months of follow-up. Of these cases, 78 hips in 69 patients were confirmed as D/I clinically (by negative Ortolani test) and radiographically. However, 17 patients (19 hips) were lost to follow-up before 20 months so have been excluded from analysis. Therefore, 59 hips in 52 patients (41 female, 11 male) met inclusion criteria for this study. Mean chronological age at diagnosis was 1.9 months (range, 0.1 to 5.9 mo). There were 33 unilateral left, 12 unilateral right and 7 bilateral cases, 40 left and 19 right hips in total. Radiologic confirmation of hip status was made by ultrasound in 56/59 hips, whereby the femoral head had <10% coverage at rest9 and did not improve/enlocate sonographically on dynamic testing. Radiographic diagnosis was made in 3/59 hips (3 patients aged 3.7, 4.9, and 5.9 mo). These were IHDI grade III/IV hips and were clinically Ortolani negative. Pavlik harness was the initial method of treatment for 46/59 hips (40/52 patients). One patient (2 hips) had Pavlik treatment after failed Denis-Browne brace. The Pavlik harness and alternative management groups are analyzed separately below.

Radiologic confirmation of hip status was made by ultrasound in 56/59 hips, whereby the femoral head had <10% coverage at rest9 and did not improve/enlocate sonographically on dynamic testing. Radiographic diagnosis was made in 3/59 hips (3 patients aged 3.7, 4.9, and 5.9 mo). These were IHDI grade III/IV hips and were clinically Ortolani negative. Pavlik harness was the initial method of treatment for 46/59 hips (40/52 patients). One patient (2 hips) had Pavlik treatment after failed Denis-Browne brace. The Pavlik harness and alternative management groups are analyzed separately below. Non-Pavlik Harness Management Although Pavlik harness was the primary method of treatment for the majority of cases, and is the primary focus of this paper, alternative treatment methods were used for 13 hips (12 patients, Table 1). Specifically, 3 hips (2 patients) had alternative braces applied first and 10 patients were treated by primary open or closed reduction surgery. All reductions were successfully maintained through follow-up. Surgical patients were diagnosed at a mean age of 4.0 months (range, 1.4 to 5.9) while mean age at surgery was 7.5 months (range, 3.2 to 11.7). TABLE 1 Patients With D/I Hips Managed by Alternative First-line Treatments to Pavlik Harness

Non-Pavlik Harness Management Although Pavlik harness was the primary method of treatment for the majority of cases, and is the primary focus of this paper, alternative treatment methods were used for 13 hips (12 patients, Table 1). Specifically, 3 hips (2 patients) had alternative braces applied first and 10 patients were treated by primary open or closed reduction surgery. All reductions were successfully maintained through follow-up. Surgical patients were diagnosed at a mean age of 4.0 months (range, 1.4 to 5.9) while mean age at surgery was 7.5 months (range, 3.2 to 11.7). TABLE 1 Patients With D/I Hips Managed by Alternative First-line Treatments to Pavlik Harness Pavlik Harness Management In total, 48 D/I hips in 41 infants were treated in Pavlik harness, including the patient treated following failure of the Denis-Browne splint. All infant Pavlik harness programmes commenced with full time wear (23 or 24 h/d). All centers used repeated clinical and sonographic assessment at ~2 week intervals to monitor hip position and provide Pavlik harness adjustments. Weaning regimes and total length of harness duration varied among centers according to local guidelines. There were 32 left and 16 right hips, including 7 patients with bilateral D/I hips. Of the 48 D/I hips, 27 were treated successfully in Pavlik harness (56.3%). Total time in Pavlik harness ranged from 43 to 106 days. Intercentre variation exists in duration and weaning regimes, though all centers started with full time wear (23 or 24 h/d). Some patients received continued treatment in a Rhino Cruiser brace beyond their time in Pavlik harness. The remaining 21/48 hips (43.7%) failed Pavlik harness treatment, requiring alternative management to achieve reduction. Two patients (3 hips) had Pavlik harness abandoned due to femoral nerve palsy (that subsequently resolved with harness removal) and the remainder due to failure to achieve reduction. Pavlik treatment in this group was abandoned early due to risk of avascular necrosis (AVN) and acetabular wear from persistently dislocated hips in harness. However, in one case continued sonographic improvement was demonstrated and Pavlik treatment was continued for 69 days. Subanalysis according to laterality, contralateral hip status, sex, and age is stratified below.

e to risk of avascular necrosis (AVN) and acetabular wear from persistently dislocated hips in harness. However, in one case continued sonographic improvement was demonstrated and Pavlik treatment was continued for 69 days. Subanalysis according to laterality, contralateral hip status, sex, and age is stratified below. Patient Demographics Patients successfully treated by Pavlik (27 hips) were a mean of 1.2 months old at diagnosis (range, 0.1 to 4.0) while those failing Pavlik (21 hips) were a mean of 1.6 months (range, 0.1 to 4.0). This age difference in age was not statistically significant (P=0.22). Likewise, patient sex had no bearing on the chance of successful Pavlik treatment (P=0.61). Affected Hip Laterality Laterality had a statistically significant effect on outcome. Specifically, 22/32 left D/I hips were successfully concentrically reduced by Pavlik harness treatment (68.8%). In contrast, only 5/16 right hips (31.2%) were comparably reduced (P=0.01). Contralateral Hip Status The contralateral hip was abnormal in 20/41 patients (48.8%), 7 of whom had bilateral D/I hips (14 hips). These 7 patients were all treated by Pavlik harness. Successful reduction was achieved in both hips of 2 patients, the left hip of 1 patient, and in neither hips of 4 patients. These 9 persistently dislocated hips were treated with closed or open reductions. The contralateral hip was involved to a lesser degree in another 13 patients. Specifically, 8 contralateral hips were reducibly dislocated (D/R), 2 were dislocatable, and 3 were dysplastic.

Contralateral Hip Status The contralateral hip was abnormal in 20/41 patients (48.8%), 7 of whom had bilateral D/I hips (14 hips). These 7 patients were all treated by Pavlik harness. Successful reduction was achieved in both hips of 2 patients, the left hip of 1 patient, and in neither hips of 4 patients. These 9 persistently dislocated hips were treated with closed or open reductions. The contralateral hip was involved to a lesser degree in another 13 patients. Specifically, 8 contralateral hips were reducibly dislocated (D/R), 2 were dislocatable, and 3 were dysplastic. Contralateral hip status did not appear to be correlated with successful reduction in Pavlik harness (P=0.32). Subanalysis of the bilateral D/I hips in comparison with those patients with a normal or lesser affected contralateral hip trended toward a difference in treatment success; however, larger numbers will be needed to demonstrate significance of this result (P=0.07).

d with successful reduction in Pavlik harness (P=0.32). Subanalysis of the bilateral D/I hips in comparison with those patients with a normal or lesser affected contralateral hip trended toward a difference in treatment success; however, larger numbers will be needed to demonstrate significance of this result (P=0.07). Management Following Failed Pavlik Treatment In total, 21 D/I hips failed Pavlik harness treatment. Alternative braces were subsequently used to treat 5 hips, all unilateral. One patient had a Denis-Browne brace applied which achieved reduction. The remaining 4 patients were switched to a Rhino brace, achieving reduction in one case. The 19 hips that failed all harness treatment (Pavlik/Rhino) were subsequently successfully treated with closed (7 hips) or open (12 hips) reduction. The average age at surgery was 7.5 months (range, 3.2 to 11.7) and the average time between brace abandonment and surgery was 4.0 months (range, 0 to 11.0). All surgical decision making was by the treating surgeon, using their own techniques, under general anesthetic. All procedures were performed by pediatric orthopaedic surgeons whose subspeciality is DDH. Subanalyis of these outcomes is beyond the scope of this paper.

nment and surgery was 4.0 months (range, 0 to 11.0). All surgical decision making was by the treating surgeon, using their own techniques, under general anesthetic. All procedures were performed by pediatric orthopaedic surgeons whose subspeciality is DDH. Subanalyis of these outcomes is beyond the scope of this paper. Patient Follow-up All hips included in this study had at least 20 months of clinical and radiographic follow-up from diagnosis (median, 25.9 mo; range, 20.0 to 58.0). All hips were radiographically classified by IHDI grade at final follow-up, with 53/59 hips IHDI grade 1 and 6/59 IHDI grade 2.8 A higher acetabular index (AI) was found in hips failing to reduce in Pavlik [mean, 26.0 degrees; range, 10 to 40 degrees, 95% confidence interval (CI), 23.2-28.7] compared with those successfully treated (mean, 20.0 degrees; range, 12 to 25 degrees; CI, 18.6-21.4). No difference was found in comparison with those treated by alternative methods (mean, 24.5 degrees; 95% CI, 20.9-28.2). No patient had subsequent surgery for residual acetabular dysplasia within the follow-up period.

compared with those successfully treated (mean, 20.0 degrees; range, 12 to 25 degrees; CI, 18.6-21.4). No difference was found in comparison with those treated by alternative methods (mean, 24.5 degrees; 95% CI, 20.9-28.2). No patient had subsequent surgery for residual acetabular dysplasia within the follow-up period. Complications Five patients experienced complications: 2 patients (3 hips) developed femoral nerve palsy in Pavlik, resulting in 2 subsequent successful closed reductions and 1 successful open reduction. Four patients developed AVN—2 managed in Pavlik and 2 managed by initial closed reduction and spica casting. AVN was diagnosed at 14 and 22 months of age in the closed reduction patients. In the patients managed by Pavlik, AVN was diagnosed at 18 months of age for 1 patient following 3 weeks of unsuccessful Pavlik harness treatment aged 3 months and a closed reduction aged 11 months. The other patient was 24 months old when AVN was diagnosed, having had femoral nerve palsy in Pavlik harness, followed by a staged successful open reduction aged 11 months. DISCUSSION This study is the largest cohort of patients to date with D/I hips. This is the most severe form of DDH, but the 56.3% success rate reported here is one of the highest success rates in the literature for this particular diagnosis.3–6 Pavlik harness treatment has been demonstrated to be a safe and sensible first-line treatment for these infants, but should be undertaken only when supported by close clinical and sonographic monitoring in experienced hands. Families should also be counselled accordingly.

he literature for this particular diagnosis.3–6 Pavlik harness treatment has been demonstrated to be a safe and sensible first-line treatment for these infants, but should be undertaken only when supported by close clinical and sonographic monitoring in experienced hands. Families should also be counselled accordingly. Contrary to previous evidence in infants below 6 months old,3,4,6 age has not been shown here to be correlated with success/failure. Pavlik harnesses for D/I hips were used successfully in infants up to the age of 4 months in this study, with age at harness initiation showing no statistical association with treatment success. As an observational study, treatment was according to each practicing surgeon at each contributing center. We intended to examine all patients enrolled in the study who were diagnosed with an irreducibly dislocated hip under 6 months of age. After identifying this cohort of patients, the observation of treatment in this group was that no infant diagnosed over 4 months was initially trialled in a Pavlik harness. Two infants in this group aged between 4 and 6 months were treated with primary surgery, as per the decision of the surgeon.

under 6 months of age. After identifying this cohort of patients, the observation of treatment in this group was that no infant diagnosed over 4 months was initially trialled in a Pavlik harness. Two infants in this group aged between 4 and 6 months were treated with primary surgery, as per the decision of the surgeon. Affected hip laterality did appear associated to Pavlik success (P=0.01). Right hips fared worse than left, raising questions on the nature of the right hip pathology. In DDH, left hips are more commonly affected than right, most likely due to the most common intrauterine position being left occiput anterior. In this position, the left hip lies adducted against the maternal sacrum, potentially placing it at greater risk for dislocation.10 Fetal positioning, such as the right occiput anterior position in which the right hip lies against the sacrum, may underlie the potential reason why right D/I hips are more sinister than left. This finding warrants further investigation. This cohort contained more female than male individuals, consistent with existing literature.2 Some authors believe that male individuals are harder to treat,11 but the current study does not support that in the D/I hip spectrum (male vs. female Pavlik harness success rate P=0.61, Table 1).

Affected hip laterality did appear associated to Pavlik success (P=0.01). Right hips fared worse than left, raising questions on the nature of the right hip pathology. In DDH, left hips are more commonly affected than right, most likely due to the most common intrauterine position being left occiput anterior. In this position, the left hip lies adducted against the maternal sacrum, potentially placing it at greater risk for dislocation.10 Fetal positioning, such as the right occiput anterior position in which the right hip lies against the sacrum, may underlie the potential reason why right D/I hips are more sinister than left. This finding warrants further investigation. This cohort contained more female than male individuals, consistent with existing literature.2 Some authors believe that male individuals are harder to treat,11 but the current study does not support that in the D/I hip spectrum (male vs. female Pavlik harness success rate P=0.61, Table 1). There is conflicting evidence whether bilateral dislocated hips are harder to treat than unilateral.3,6,12 However, this study has not found statistical significance to support this belief specifically for D/I hips. For unilateral D/I cases, the status of the contralateral hip was not found to influence success rates (P=0.32). This comparison held true whether the contralateral hip was reducibly dislocated, dislocatable, dysplastic, or normal. Bilateral D/I hips had a lower chance of successful reduction in Pavlik harness compared with unilateral D/I hips, though this did not reach significance (P=0.07). However, numbers were small and further study is required.

true whether the contralateral hip was reducibly dislocated, dislocatable, dysplastic, or normal. Bilateral D/I hips had a lower chance of successful reduction in Pavlik harness compared with unilateral D/I hips, though this did not reach significance (P=0.07). However, numbers were small and further study is required. Femoral nerve palsy was a reason for the Pavlik harness needing to be abandoned. Although few studies have specifically examined femoral nerve palsy in dislocated hips, one retrospective study reported that this complication is more likely in the more severe grades of DDH.13 In addition, there is a lack of studies examining incidence of femoral nerve palsy following brace treatment specifically in dislocated hips, as Murnaghan and colleagues include hips across the entire DDH spectrum. Therefore, femoral nerve palsy incidence in dislocated hips may be an underappreciated iatrogenic complication. In this regard, 2 of 41 infants (5%) affected in this cohort may actually be a commendably low incidence in this severe DDH group.

ips, as Murnaghan and colleagues include hips across the entire DDH spectrum. Therefore, femoral nerve palsy incidence in dislocated hips may be an underappreciated iatrogenic complication. In this regard, 2 of 41 infants (5%) affected in this cohort may actually be a commendably low incidence in this severe DDH group. AVN of the femoral head (Pavlik harness disease) is almost exclusively in those hips that are dislocated initially. However, the alternative to a Pavlik harness is surgical reduction. Closed reduction has invariably higher AVN rates in this patient group than the proportions observed in this paper with Pavlik harness treatment. All cases of AVN recorded in the larger study database to dae arose following either closed or open reduction. We recognize that some of these patients had previously undergone failed harness treatment, and as such, cannot discount the possibility that AVN may have been at least partially due to said harness. However, in our analyses of these surgical patient cohorts, the development of AVN did not seem to be associated with prior bracing attempts. These analyses are admittedly preliminary with small numbers and limited follow-up.

cannot discount the possibility that AVN may have been at least partially due to said harness. However, in our analyses of these surgical patient cohorts, the development of AVN did not seem to be associated with prior bracing attempts. These analyses are admittedly preliminary with small numbers and limited follow-up. This study is limited by having patient follow-up data to a median of only 2 years. Although no patient has required subsequent surgery for residual dysplasia, dysplasia may persist or appear beyond this age and many centers may perform this surgery, if needed, around the age of 4 to 5 years.2 This would therefore fall beyond the timeframe of this study. Extended follow-up is required to gain a complete understanding of treatment success. However, there are early indications of promise within this group of patients. Specifically, IHDI radiograph scores at 2 years are either grade 1 or 2 and only 4 patients have an AI >30 degrees, with the highest AI being 40 degrees. Although all studies have a standardized infant position for radiographs, we recognize the difficulty in infant positioning which may increase error in measurement. The Pavlik treatment failure group was found to have a significantly higher AI at final follow-up. AVN rate is possibly under-reported as follow-up is currently too short for some growth disturbance to appear. This study is further limited by those 17 of 69 patients lost to follow-up. These were largely due to patients emigrating.

reatment failure group was found to have a significantly higher AI at final follow-up. AVN rate is possibly under-reported as follow-up is currently too short for some growth disturbance to appear. This study is further limited by those 17 of 69 patients lost to follow-up. These were largely due to patients emigrating. A recognized limitation of this study, consistent with the nature of multicentre observational studies, is the lack of standardized surgical technique between surgeons and across centers. We cannot control for differences in technique between surgeons, thus all studies resulting from these data should be considered effectiveness studies not efficacy studies. This is the largest prospective study to date on D/I hips, with a cohort of 52 patients (59 hips). However, these numbers are still small and there may be type 2 errors in all tests where no difference was found, such as with bilateral D/I hips (P=0.07). We also cannot exclude the possibility of type 1 errors for the effect of hip laterality. The follow-up is insufficient to determine the long-term complication rate of any of these treatment methods; consequently, these results should be viewed as hypothesis-generating for future studies. Success rates have been compared within groups, but ideally regression analysis is required to generate true predictors of success in treatment modalities, for which much larger numbers of failed treatment are required.

t methods; consequently, these results should be viewed as hypothesis-generating for future studies. Success rates have been compared within groups, but ideally regression analysis is required to generate true predictors of success in treatment modalities, for which much larger numbers of failed treatment are required. Clinical examination of hip stability is not fully reliable.14,15 This study only included patients who had radiologic confirmation of an irreducible dislocation, unlike previous studies on D/I hips.3–6 Therefore, 18 hips (15 patients) were excluded for this reason. A further 10 hips in 9 patients were D/I on clinical examination, but were found to be reducible on ultrasound. These were also excluded and support the evidence for imperfect reliability of clinical examinations.

n, unlike previous studies on D/I hips.3–6 Therefore, 18 hips (15 patients) were excluded for this reason. A further 10 hips in 9 patients were D/I on clinical examination, but were found to be reducible on ultrasound. These were also excluded and support the evidence for imperfect reliability of clinical examinations. There are a number of studies in the DDH literature that examine the success rate of Pavlik harness treatment for hip dislocations. Typically, these studies are examining infants with a mixed spectrum of DDH severity. Irreducible dislocations have been included in some of these studies we reference in the introduction.3–6 Therefore, there is past clinical precedent, despite an incomplete understanding of the true success/failure rate specifically in this cohort. With an orthotic, hips are held in the protective position of abduction and flexion, rather than extension. This was neatly demonstrated by Salter16 in his porcine studies. Over time the hip can be observed to reduce. This is observed by weekly sonographic assessments and the position can be noted to improve. Failure to improve/reduce is a reason to abandon harness, and this decision is typically made in the first week or so. The specific intent behind using an orthosis as first-line management would be that if there is a potential for successful reduction, and minimal adverse effects of a failed attempt, then more complex and invasive surgical treatment can be avoided for at least some of these patients.

cally made in the first week or so. The specific intent behind using an orthosis as first-line management would be that if there is a potential for successful reduction, and minimal adverse effects of a failed attempt, then more complex and invasive surgical treatment can be avoided for at least some of these patients. There still remains considerable variation in treatment strategies across and within centers treating DDH. These discrepancies make direct comparison more challenging. Hips treated by alternative methods to a Pavlik harness (11 hips) are included in this study in a descriptive manner only. On the basis of this study alone, recommendations cannot be made on these treatment methods. Furthermore, variability exists in Pavlik harness regimes. Timing of application, duration, weaning, and whether the treatment is guided by serial ultrasound or clinical examination may all have implications on management of DDH. This study does not yet have sufficient power to explore these variables in this particular patient group. Despite these limitations, this study is the largest cohort of D/I hips to be analyzed and has stratified factors to help guide treatment. The use of Pavlik harness as a first-line management for D/I hips is supported, with success demonstrated up to 4 months of age. The right D/I hip was shown to be particularly difficult to treat and failure of Pavlik treatment is associated with higher residual AI’s. Ongoing recruitment and follow-up within the multicenter database will allow further examination of this very difficult patient group.

th success demonstrated up to 4 months of age. The right D/I hip was shown to be particularly difficult to treat and failure of Pavlik treatment is associated with higher residual AI’s. Ongoing recruitment and follow-up within the multicenter database will allow further examination of this very difficult patient group. ACKNOWLEDGMENTS Additional contributing members of the IHDI Study Group are: Nicole Williams, Bruce Foster, Peter Cundy, Travis Matheney, James Kasser, Young-Jo Kim, Pablo Castaneda, Wudbhav Sankar, Vidyadhar Upasani, Scott Mubarak, John Wedge, Unni Narayanan, Colin Moseley, Ernie Sink. Supported by International Hip Dysplasia Institute. The authors declare no conflicts of interest.

Letterer-Siwe disease, Hand-Schuller-Christian disease, and eosinophilic granuloma, previously believed to be 3 different diseases, are now known to be different presentations of a single disease process [Langerhans cell histiocytosis (LCH)] distinguished by the clonal proliferation of Langerhans cells.1,2 Many reports on patients with LCH of the spine are well described in the literature, and the clinical findings were first reported by Calve in 1925. The incidence of LCH with spine lesions in children is ∼20% to 30%.3 However, vertebral collapse commonly occurs in pediatric LCH patients and induces local kyphosis of the sagittal alignment at the affected site during early stages. Spontaneous recovery of the compression fracture is a characteristic of this disease. Most previous studies have focused on the results at discontinuous timing including onset and final visit. Few reports have demonstrated in detail the longitudinal assessment for vertebral remodeling. Therefore, this study aimed to investigate the longitudinal changes in the affected vertebrae and the adjacent disk and vertebrae in children with spinal LCH, aged below 8 years, within the first 7 years after disease onset.

. Few reports have demonstrated in detail the longitudinal assessment for vertebral remodeling. Therefore, this study aimed to investigate the longitudinal changes in the affected vertebrae and the adjacent disk and vertebrae in children with spinal LCH, aged below 8 years, within the first 7 years after disease onset. METHODS We recruited 13 patients (9 girls and 4 boys) including 16 affected vertebrae. All patients were aged below 8 years. They were diagnosed with LCH by histologic assessment via biopsy. Biopsy is not always necessary to diagnose this condition. However, in this study, we recruited only patients with pathologic diagnosis via biopsy to maintain a high accuracy of diagnosis for research purposes. Children with C1 lesions were excluded from this study. The average age at first visit was 3.6 years (range, 1.4 to 7.8 y), and the average follow-up period was 10.2 years (range, 5 to 21 y). A single lesion was observed in 5 patients, whereas multiple lesions were observed in the remaining 8 patients who received chemotherapeutic treatment, including 2 patients with organ involvement. Nine patients used a brace for 3 months to 6 years, and 4 patients were treated with supervised neglect. Vertebral lesions involved L2 in 3 cases; T12, L1, or L5 in 2 cases; and C4, C5, C7, T5, T8, T9, or L3 in 1 case.

ning 8 patients who received chemotherapeutic treatment, including 2 patients with organ involvement. Nine patients used a brace for 3 months to 6 years, and 4 patients were treated with supervised neglect. Vertebral lesions involved L2 in 3 cases; T12, L1, or L5 in 2 cases; and C4, C5, C7, T5, T8, T9, or L3 in 1 case. First, we measured the ratios of the height of the affected vertebra and one vertebra above the affected one to that of the second vertebra above the affected one (AA/A2, CA/C2, PA/P2, A1/A2, C1/C2, and P1/P2), as the indices of the collapse and reconstitution of the affected vertebra and the influence of adjacent vertebra. Next, we measured the ratio of the height of the center of the adjacent disk to that of the one disk above it (DD) and the local kyphosis angle to define the transformation of the adjacent disk and the shift in the sagittal alignment. We made these radiographic measurements using sagittal x-ray films obtained with the patient in a standing position (Fig. 1). In addition, we assessed the influence of chemotherapy and brace treatment on the recovery of vertebral collapse using CA/C2.

mation of the adjacent disk and the shift in the sagittal alignment. We made these radiographic measurements using sagittal x-ray films obtained with the patient in a standing position (Fig. 1). In addition, we assessed the influence of chemotherapy and brace treatment on the recovery of vertebral collapse using CA/C2. FIGURE 1 Radiographic measurements. AA/A2 indicates the ratio of the height of the anterior wall of the affected vertebra to that of the 2 above vertebra; A1/A2, the ratio of the height of the anterior wall of the 1 above vertebra to that of the 2 above vertebra; CA/C2, the ratio of the height of the center of the affected vertebra to that of the 2 above vertebra; C1/C2, the ratio of the height of the center of the 1 above vertebra to that of the 2 above vertebra; DD, the ratio of the adjacent disk (D1) to the one above disk (D2); LKA, local kyphosis angle; PA/P2, the ratio of the height of the posterior wall of the affected vertebra to that of the 2 above vertebra; P1/P2, the ratio of the height of the posterior wall of the 1 above vertebra to that of the 2 above vertebra. We examined patient data until 7 years after disease onset as the data for this period had only few missing entries. Statistical differences between first visit and other timings were analyzed using the Wilcoxon signed-rank test. A probability value of <0.05 was considered statistically significant. Data analysis was performed using SPSS package version 24 (IBM Corporation, Armonk, NY).

a for this period had only few missing entries. Statistical differences between first visit and other timings were analyzed using the Wilcoxon signed-rank test. A probability value of <0.05 was considered statistically significant. Data analysis was performed using SPSS package version 24 (IBM Corporation, Armonk, NY). RESULTS Tables (Supplemental Digital Content 1,http://links.lww.com/BPO/A186) show the data of the collapsed vertebra, local kyphosis angle, and the adjacent structures. The Index of Vertebral Collapse and Local Kyphosis In the affected vertebra, the posterior wall height remained in the collapse phase and the most severe collapse was noted not at the first visit but 1 year after disease onset. The recovery speed of the anterior wall tended to be faster than that of the center. The rate of reconstitution accelerated at 2 years or later. However, complete reconstitution was not achieved at the final visit (7 years after onset). Patients acquired lordosis alignment within the first 3 years. Patients who received chemotherapy had a tendency to show a lower rate of vertebral collapse of the affected vertebra and the faster recovery (P<0.05 at 5 and 6 y after onset) (Supplemental Digital Content 2, http://links.lww.com/BPO/A187). There was no statistical difference between the patients with and without brace treatment (Supplemental Digital Content 3, http://links.lww.com/BPO/A188).

ertebral collapse of the affected vertebra and the faster recovery (P<0.05 at 5 and 6 y after onset) (Supplemental Digital Content 2, http://links.lww.com/BPO/A187). There was no statistical difference between the patients with and without brace treatment (Supplemental Digital Content 3, http://links.lww.com/BPO/A188). The Index of the Transformation of the Adjacent Structures The height of the adjacent disk increased during a severe collapse phase of the affected vertebra. In addition, the height of adjacent vertebra increased in the same phase. Figure 2 shows the schema of the reconstitution of spinal LCH in this series (Fig. 3). FIGURE 2 The schema of the reconstitution of spinal Langerhans cell histiocytosis at the lumbar site. After disease onset, the transformations of the adjacent structures occurred to recover the spinal alignment. As the affected vertebra reconstituted, the augmentation of the adjacent disk and vertebra gradually diminished. FIGURE 3 Case presentation. Spinal Langerhans cell histiocytosis at L1 in a 3-year-old girl. A, First visit: the affected vertebra showed severe collapse and caused local kyphosis. The heights of the adjacent disks had already increased. B, After 2 years, the affected vertebra had shown a tendency to recover and the heights of the adjacent disks and vertebrae were increased. C, At final visit (12 y old), the height of the affected vertebra was comparable to the other healthy vertebra. The heights of adjacent disks and vertebrae were almost normal.

sed. B, After 2 years, the affected vertebra had shown a tendency to recover and the heights of the adjacent disks and vertebrae were increased. C, At final visit (12 y old), the height of the affected vertebra was comparable to the other healthy vertebra. The heights of adjacent disks and vertebrae were almost normal. DISCUSSION The vertebral height in children with spinal LCH gradually recovered, despite the almost complete collapse of the affected vertebra at disease onset.4,5

sed. B, After 2 years, the affected vertebra had shown a tendency to recover and the heights of the adjacent disks and vertebrae were increased. C, At final visit (12 y old), the height of the affected vertebra was comparable to the other healthy vertebra. The heights of adjacent disks and vertebrae were almost normal. DISCUSSION The vertebral height in children with spinal LCH gradually recovered, despite the almost complete collapse of the affected vertebra at disease onset.4,5 Several treatments for bony LCH lesions have been reported including supervised observation, steroid injections, curettage with/without a bone graft, chemotherapy, and irradiation. With a variety of treatment options, most of the patients responded well, and there is no evidence suggesting that one treatment is more advantageous than another.6 In the present study, the patients who were treated with chemotherapy tended to show a lower percentage of vertebral collapse at an early stage and faster recovery. To the best of our knowledge, there is no study reporting the effect of chemotherapy on the recovery of collapsed vertebrae. We believe that bed rest may be one of the factors preventing vertebral collapse because chemotherapy requires in-hospital treatment. The other factor may be the site of the affected vertebra. The nonchemotherapy cases included 3 vertebrae in thoracic spine. The resilience of cervical and lumbar vertebrae, which represent lordosis alignment, was better than that of thoracic vertebrae, which represent kyphosis alignment. However, the small sample size is a limitation of this study, and we need further research to explain this result. Specifically, for the treatment of spinal LCH, most physicians seem to consider immobilization with a brace as the initial treatment. Several studies have reported that immobilization is adequate for most patients.7 We agreed with Greenlee et al’s8 suggestion that the brace can be removed after the pain is resolved. Although we tried to compare outcomes between the groups with and without brace treatment in this series, there was no significant difference in the reconstitution of the affected vertebrae and the spinal alignment. Thus, we believe that there are no advantages of long-term use of braces.

ed after the pain is resolved. Although we tried to compare outcomes between the groups with and without brace treatment in this series, there was no significant difference in the reconstitution of the affected vertebrae and the spinal alignment. Thus, we believe that there are no advantages of long-term use of braces. Several studies have reported that the best reconstitution of vertebral height was noted after skeletal maturity, and adolescence or at least 4 years before the development of skeletal maturity is an appropriate time for vertebral remodeling.9,10 Raab et al11 reported that the degree of reconstitution does not change based on the involved site: cervical, thoracic, or lumbar portion. In our study, 13 of 16 affected vertebrae were located at the physiological lordosis site (cervical and lumbar portion). The collapse of the affected vertebra was most severe 1 year after disease onset. Then, the affected vertebra gradually recovered. Finally, overall results of this series headed toward lordosis alignment. Meanwhile, the final recovery height of the affected vertebrae reported in previous studies9–11 was better than that reported in this study. Therefore, our results only indicate reconstitution at the early stage of the disease (only 7 years after onset).

overall results of this series headed toward lordosis alignment. Meanwhile, the final recovery height of the affected vertebrae reported in previous studies9–11 was better than that reported in this study. Therefore, our results only indicate reconstitution at the early stage of the disease (only 7 years after onset). Local kyphosis also improved in the same manner. Intriguingly, the recovery speed from kyphosis to lordosis was faster than the recovery speed of the affected vertebral height. Thus, we investigated the transformation of the adjacent disks and vertebrae. As a result, 1 and 2 years after onset, the period with the maximum collapse of the affected vertebra, the heights of not only the adjacent disk but also the adjacent vertebra increased. We could not determine whether it was overgrowth or an augmentation change. We often see the similar phenomenon in early-onset scoliosis children with implanted growing rods, who show vertebral body growth by the growth-stimulating effect of the distraction force that the growing rod produces based on Hueter-Volkmann principle.12–15 Similarly, considering that the final alignment in this series leads toward lordosis alignment, there is a possibility of a small effect of reduced axial pressure or the relative distraction force at the adjacent site of the collapsed vertebrae. We need more bioengineering studies in the future to validate this hypothesis. After the onset, the transformations of the adjacent structures occurred as if to augment the spinal alignment. These transformations affected the positive realignment of the sagittal balance at the earlier stage of the disease. Then, based on the reconstitution of the affected vertebra, the augmentation of the adjacent disk and vertebra gradually diminished. There are no reports that have discussed the changes of the adjacent disks and vertebrae in detail.

d the positive realignment of the sagittal balance at the earlier stage of the disease. Then, based on the reconstitution of the affected vertebra, the augmentation of the adjacent disk and vertebra gradually diminished. There are no reports that have discussed the changes of the adjacent disks and vertebrae in detail. In this study, the average age at disease onset was 3.6 years. Moreover, very young children have better bone remodeling potential. Greenlee et al8 suggested that younger patients have greater potential for recovery of vertebral height. However, Levine et al13 reported varying degrees of reconstitution of vertebral height and noted no correlation between age and the degree of reconstitution. With regard to this point, the results of the present study remained controversial. Hence, further studies are needed to determine the transformation of the adjacent disk and vertebrae among adolescents. Supplementary Material SUPPLEMENTARY MATERIAL Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.pedorthopaedics.com. The authors have no financial relationship to disclose. The authors declare no conflicts of interest.

Encompassing a spectrum from mild dysplasia to frank dislocation, developmental dysplasia of the hip (DDH) is one of the most common developmental deformities of the lower extremities and one of the leading causes of future osteoarthritis and hip arthroplasty.1,2 The goal of treatment is to achieve a stable, concentric reduction to facilitate normal femoral head development and continued acetabular growth and remodeling.2–4 For those infants who fail initial nonsurgical management, or those who present late, treatment often involves closed reduction (CR) and spica casting.2,5 Although this procedure is generally successful,2 concerns persist about the risk for iatrogenic avascular necrosis (AVN) of the femoral head and its associated impact on long-term outcomes and function.3,6–8 Other adverse outcomes may include redislocation and the need for further corrective surgery to address residual dysplasia.2,5

rocedure is generally successful,2 concerns persist about the risk for iatrogenic avascular necrosis (AVN) of the femoral head and its associated impact on long-term outcomes and function.3,6–8 Other adverse outcomes may include redislocation and the need for further corrective surgery to address residual dysplasia.2,5 Although a variety of demographic and baseline characteristics have been proposed to influence outcomes, conflicting reports have often been described for each. Because of the mixed results following a failure of reduction, as well as the long-term negative impact of AVN, the role of CR in the management of DDH is increasingly being questioned. There is, however, a relative dearth of prospectively collected data guiding such decision-making. Therefore, the purpose of this multicenter study group was to establish a representative cohort of dislocated hips that may be followed prospectively to ascertain accurate long-term success and complications rates following CR for infantile DDH. For this investigation, the authors sought to determine early-term outcomes following CR, as well as potential risk factors for failure of therapy and the future development of AVN.

ed hips that may be followed prospectively to ascertain accurate long-term success and complications rates following CR for infantile DDH. For this investigation, the authors sought to determine early-term outcomes following CR, as well as potential risk factors for failure of therapy and the future development of AVN. METHODS The data for this study were queried from a prospectively collected database of a multicenter, international study group [International Hip Dysplasia Institute (IHDI)]. Institutional review board approval was obtained by all sites before patient enrollment. At each encounter, contributing surgeons collected and uploaded all relevant patient information and pertinent clinical details to a central database, including most recent hip radiographs. This deidentified database was then queried between 2009 and December 2014 to identify all patients below 18 months of age at initial diagnosis who were treated with CR for DDH. All hips were frankly dislocated by ultrasound (≤35% femoral head coverage)9,10 and/or radiograph (IHDI grade ≥3)11 at the time of CR. Bilateral hips were counted separately. Fourteen hips were excluded for <12 months radiographic follow-up postreduction. As demonstrated in Figure 1, patients treated with open reduction at any time following the index CR were noted and separated from the final cohort FIGURE 1 CONSORT (Consolidated Standards of Reporting Trials) diagram showing patients evaluated, excluded, and enrolled by stage, along with primary and secondary outcomes at latest radiographic follow-up.

METHODS The data for this study were queried from a prospectively collected database of a multicenter, international study group [International Hip Dysplasia Institute (IHDI)]. Institutional review board approval was obtained by all sites before patient enrollment. At each encounter, contributing surgeons collected and uploaded all relevant patient information and pertinent clinical details to a central database, including most recent hip radiographs. This deidentified database was then queried between 2009 and December 2014 to identify all patients below 18 months of age at initial diagnosis who were treated with CR for DDH. All hips were frankly dislocated by ultrasound (≤35% femoral head coverage)9,10 and/or radiograph (IHDI grade ≥3)11 at the time of CR. Bilateral hips were counted separately. Fourteen hips were excluded for <12 months radiographic follow-up postreduction. As demonstrated in Figure 1, patients treated with open reduction at any time following the index CR were noted and separated from the final cohort FIGURE 1 CONSORT (Consolidated Standards of Reporting Trials) diagram showing patients evaluated, excluded, and enrolled by stage, along with primary and secondary outcomes at latest radiographic follow-up. The database was designed to collect patient information and clinical details for each included hip from the time of initial consultation through most recent follow-up. All radiographic measurements, except AVN, were utilized as originally entered by the treating surgeon. The presence or absence of AVN by most recent follow-up was determined by independent, blinded assessment of follow-up radiographs by 3 authors from 3 different institutions (W.N.S., K.M., C.T.P.); group consensus was reached for any discrepancies. Each reviewer based their designations on the Salter criteria,12–14 but for the purposes of this manuscript each hip was only classified with a simple “yes” versus “no” for radiographic evidence of AVN to reduce subtype variability (Figs. 2A–C). Secondary outcomes included residual dysplasia (acetabular index and IHDI grade11), redislocation rate, and the need for further corrective surgery. Failure of CR was defined as either an open reduction at any time following the index reduction and/or an IHDI grade 3 or 4 hip at most recent radiographic follow-up.

–C). Secondary outcomes included residual dysplasia (acetabular index and IHDI grade11), redislocation rate, and the need for further corrective surgery. Failure of CR was defined as either an open reduction at any time following the index reduction and/or an IHDI grade 3 or 4 hip at most recent radiographic follow-up. FIGURE 2 A, AP view of the right hip demonstrating a normal-appearing hip 36 months following closed reduction. B, AP view of the right hip demonstrating epiphyseal fragmentation 23 months following closed reduction, which was classified as AVN. C, AP view of the left hip 18 months following closed reduction demonstrating absence of the ossific nucleus and broadening of the femoral neck, which was also classified as AVN. AP indicates anteroposterior; AVN, avascular necrosis. Statistical Analysis Comparative analyses were performed using the Fisher exact/χ2 tests, Student t tests/Mann-Whitney U test, or ANOVA. Multivariate regression was used to assess outcomes when controlling for given patient characteristics and/or clinical details. Categorical variables are reported as frequency and percentage; continuous variables are presented with a measure of central tendency (mean or median) and spread (SD or range). All comparative analyses were 2-tailed with α set at 0.05. Statistical analysis was performed using Stata (StataCorp, College Station, TX).

ls. Categorical variables are reported as frequency and percentage; continuous variables are presented with a measure of central tendency (mean or median) and spread (SD or range). All comparative analyses were 2-tailed with α set at 0.05. Statistical analysis was performed using Stata (StataCorp, College Station, TX). RESULTS A total of 78 patients (87 hips) across 7 institutions were evaluated. Median age at initial CR was 8 months (range, 1 to 20 mo; Fig. 1). Of these, 8 hips (9%) could not be successfully closed reduced on initial attempt. Hips that were irreducible on clinical and/or ultrasonographic exam were more likely to have an unsuccessful initial CR. We found no other significant differences between those that were and were not able to be successfully closed reduced (Table 1). TABLE 1 Baseline Characteristics and Details of Initial Operative Management

RESULTS A total of 78 patients (87 hips) across 7 institutions were evaluated. Median age at initial CR was 8 months (range, 1 to 20 mo; Fig. 1). Of these, 8 hips (9%) could not be successfully closed reduced on initial attempt. Hips that were irreducible on clinical and/or ultrasonographic exam were more likely to have an unsuccessful initial CR. We found no other significant differences between those that were and were not able to be successfully closed reduced (Table 1). TABLE 1 Baseline Characteristics and Details of Initial Operative Management Among infants with an initially successful CR (n=79; 91%), 34% were previously treated in brace (Pavlik harness and/or rigid abduction orthosis) for a median of 3 weeks (range, 1 to 25 wk). An adductor tenotomy was performed in 85% of infants, a psoas release in 14%, and prereduction traction in 13%. When used, prereduction traction was for an average duration of 1 week. For those with preoperative ultrasound (n=32, 41%), median femoral head coverage was 10% (range, 0% to 40%), and median α angle was 48 degrees (range, 22 to 60 degrees). For those with preoperative radiographs (n=57, 72%), the proportion of infants with a prereduction IHDI grade of 1, 2, 3, or 4 was 0%, 12%, 56%, and 32%, respectively. An ossific nucleus was present in 56% of hips. Following the initially successful CR, 90% of hips were placed into a hip spica cast (median 12 wk; range, 4 to 30 wk), and 10% were placed directly into a Denis Browne splint (median 26 wk; range, 9 to 53 wk). Of those treated with spica casting, 68% of hips were treated to some extent with a postcasting abduction orthosis (eg, Rhino cruiser, broomsticks, Denis Browne splint, etc.).

o a hip spica cast (median 12 wk; range, 4 to 30 wk), and 10% were placed directly into a Denis Browne splint (median 26 wk; range, 9 to 53 wk). Of those treated with spica casting, 68% of hips were treated to some extent with a postcasting abduction orthosis (eg, Rhino cruiser, broomsticks, Denis Browne splint, etc.). At most recent follow-up (median 22 mo; range, 12 to 36 mo), 7/79 initially successful CRs (9%) went on to fail (6 requiring open reduction; 1 with an IHDI grade of 3) (Table 2). The failures occurred at a median of 4 months (range, 1 to 6 mo) following the index reduction. Within our limited numbers, the likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). There was a nonsignificant trend toward fewer adductor releases (57% vs. 88%, P=0.065) and higher initial IHDI grades in hips that failed initial reduction. TABLE 2 Failure Following an Initially Successful Closed Reduction

At most recent follow-up (median 22 mo; range, 12 to 36 mo), 7/79 initially successful CRs (9%) went on to fail (6 requiring open reduction; 1 with an IHDI grade of 3) (Table 2). The failures occurred at a median of 4 months (range, 1 to 6 mo) following the index reduction. Within our limited numbers, the likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). There was a nonsignificant trend toward fewer adductor releases (57% vs. 88%, P=0.065) and higher initial IHDI grades in hips that failed initial reduction. TABLE 2 Failure Following an Initially Successful Closed Reduction At most recent follow-up, 67/72 (93%) hips were IHDI grade 1 and 5/72 (7%) were grade 2. According to consensus review of the radiographs, 18/72 (25%) of hips developed radiographic evidence of AVN (Table 3). The risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus at the time of reduction (P=0.496), previous treatment in brace (P=0.662), or prereduction traction (P=1.000). Hips that developed AVN had a significantly longer duration of postreduction spica casting (median 15 wk vs. 12 wk, P=0.011). There was a nonsignificant trend toward increased AVN with higher initial IHDI grade. TABLE 3 Presence of Radiographic AVN for All Hips With Successful CR at Final Follow-up

At most recent follow-up, 67/72 (93%) hips were IHDI grade 1 and 5/72 (7%) were grade 2. According to consensus review of the radiographs, 18/72 (25%) of hips developed radiographic evidence of AVN (Table 3). The risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus at the time of reduction (P=0.496), previous treatment in brace (P=0.662), or prereduction traction (P=1.000). Hips that developed AVN had a significantly longer duration of postreduction spica casting (median 15 wk vs. 12 wk, P=0.011). There was a nonsignificant trend toward increased AVN with higher initial IHDI grade. TABLE 3 Presence of Radiographic AVN for All Hips With Successful CR at Final Follow-up At latest follow-up, mean acetabular index was 25 degrees (±6 degrees), and was unaffected by any baseline characteristics or treatment details, including the presence of AVN on final radiographs (P=0.220). The Spearman correlations revealed no statistically significant linear association between age at CR and final acetabular index (P=0.553). During the follow-up period, 8/72 successfully reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/BPO/A87). Hips treated with further corrective surgery were older at the time of CR (median 14 mo vs. 8 mo, P=0.003), more likely to have an ossific nucleus present (100% vs. 52%, P=0.017), and less likely to have been treated with a prereduction brace (0% vs. 36%, P=0.049). Hips with AVN were not more likely to undergo further corrective surgery (P=1.000). Increasing severity of initial disease as measured by IHDI grade did not appear to affect the rate of further corrective surgery for residual dysplasia (P=0.362).

ely to have been treated with a prereduction brace (0% vs. 36%, P=0.049). Hips with AVN were not more likely to undergo further corrective surgery (P=1.000). Increasing severity of initial disease as measured by IHDI grade did not appear to affect the rate of further corrective surgery for residual dysplasia (P=0.362). DISCUSSION As one of the primary treatment options for infants with DDH, CR typically includes examination under anesthesia, arthrogram with/without an adductor tenotomy, and postreduction immobilization of the affected hip (eg, spica cast). Although largely successful, CR may also lead to a number of adverse complications, including AVN and loss of reduction. Most outcome data for CRs, however, are based on retrospective series. Specifically, a systematic review by Novais et al15 evaluating both open and closed management of DDH noted that “the majority of studies included were rated as being of poor methodologic quality” and that “higher quality evidence is needed to better understand” the potential risk factors for future AVN.

ective series. Specifically, a systematic review by Novais et al15 evaluating both open and closed management of DDH noted that “the majority of studies included were rated as being of poor methodologic quality” and that “higher quality evidence is needed to better understand” the potential risk factors for future AVN. In addition to establishing a representative multicenter cohort that can be followed prospectively, the purpose of this investigation was to report early outcomes following CR for DDH. At early-term follow-up (median 22 mo; range, 12 to 36 mo), our cohort had a 91% initial success rate with a 25% incidence of AVN, a 9% incidence of redislocation following an initially successful CR, and an 11% incidence of further corrective surgery. Interestingly, the likelihood of either loss of reduction or the development of AVN was unaffected by a number of characteristics frequently cited to negatively influence early outcomes, including femoral head reducibility before CR, previous orthotic bracing, age, or presence of the ossific nucleus at the time of reduction. Conversely, infants that were older at the time of CR were more likely to need further corrective surgery. Importantly, this study’s multicenter design and primary analysis by investigators not affiliated with the treating institutions limited the publication bias inherent to any single-center, self-authored cohort.

n. Conversely, infants that were older at the time of CR were more likely to need further corrective surgery. Importantly, this study’s multicenter design and primary analysis by investigators not affiliated with the treating institutions limited the publication bias inherent to any single-center, self-authored cohort. Osteonecrosis is one of the most concerning complications following CR. In recent studies (published since 2000), the incidence of AVN following CR varies widely between 2% and 36%,4,5,13,14,16–27 with Cooper et al2 noting that this disparity is “largely caused by differences in the definitions of AVN and the timing of follow-up.” Comparing closed versus open treatment, Novais et al15 reported in their recent meta-analysis an incidence of significant AVN (grade ≥2) of 8% following CR versus 19% following OR, with Clarke et al19 reporting a similar pattern of 7% and 14%, respectively. Here, our reported incidence of AVN was 25% at a median follow-up of approximately 2 years. Although some have suggested that prolonged follow-up for 10 to 12 years is necessary to ascertain the true incidence of AVN,3,6,7 others argue that follow-up beyond 2 years will not identify additional cases.14,28–30 A variety of classification criteria have also been used, and many authors differentially include low-grade changes.2 This variation in AVN definitions and lengths of follow-up highlight the importance of establishing a prospective cohort that can be followed longitudinally to determine accurate data.

al cases.14,28–30 A variety of classification criteria have also been used, and many authors differentially include low-grade changes.2 This variation in AVN definitions and lengths of follow-up highlight the importance of establishing a prospective cohort that can be followed longitudinally to determine accurate data. Multiple potential risk factors for AVN have been reported, with the presence of the ossific nucleus at the time of reduction remaining one of the most controversial. Although some authors argue that the ossific nucleus is protective against AVN,17,19,27,31 others note no such effect.18,23,24,26,29 Relatedly, whereas some have linked older age at reduction to a higher incidence of AVN but a lower rate of severe disease,3,7,18,32 others have noted that age at reduction has no effect on AVN risk.4,6,15,24,29,31 In this cohort, neither age at reduction nor the presence of an ossific nucleus was associated with the presence of AVN. Consistent with prior studies, sex, bilateral disease, family history, previous treatment with Pavlik harness/abduction orthosis, and the performance of an adductor tenotomy also did not impact disease frequency.3,6,13,17,21,29,31 Although a trend was appreciated, the limited number of patients with prereduction radiographs may have constrained our findings regarding the severity of initial dislocation (as measured by IHDI grade), which prior reports suggest may influence AVN risk.3,18,32 We did note an increased length of spica cast immobilization following CR in those who developed AVN versus those who did not. Whereas this difference was statistically significant, its clinical significance is unclear. It is possible that longer periods of casting were an indirect reflection of greater disease severity, or that there is an intrinsic ill effect on perfusion from prolonged immobilization of an infantile hip.

those who did not. Whereas this difference was statistically significant, its clinical significance is unclear. It is possible that longer periods of casting were an indirect reflection of greater disease severity, or that there is an intrinsic ill effect on perfusion from prolonged immobilization of an infantile hip. Achieving, and maintaining, a concentric reduction of the hip is one of the primary drivers of future acetabular growth and development.4,33,34 Although potential overlap is likely, rates of failed initial reduction across the literature vary between 6% and 25%,2,13,16,20,25,35,36 and rates of loss of reduction from 0% to 18%.5,13,16,20,23–25,35–37 In this cohort, 91% of hips were successfully reduced on the initial attempt, with 9% going on to fail CR at latest follow-up. Importantly, however, rates of failed initial reduction are likely to vary considerably based upon the treating surgeon’s threshold for proceeding directly to open reduction. Nevertheless, our results fall within the lower half of the previously reported ranges, suggesting reasonable success may be achieved following CR.

portantly, however, rates of failed initial reduction are likely to vary considerably based upon the treating surgeon’s threshold for proceeding directly to open reduction. Nevertheless, our results fall within the lower half of the previously reported ranges, suggesting reasonable success may be achieved following CR. Several factors have been proposed to increase risk of residual dysplasia following CR. In this study, we chose to measure residual dysplasia in 2 ways: objective acetabular measurements (acetabular index and IHDI grade) and the incidence of further corrective surgery. Regarding the former, no patient-specific factors in this cohort were predictive of worsened acetabular index, including prereduction IHDI grade, age at reduction, or final AVN status. Regarding the latter, 11% of hips in this study were treated with a subsequent acetabuloplasty and/or femoral osteotomy, although that rate will likely rise with continued follow-up. In comparison, rates of further corrective surgery across the literature range as high as 57% to 100%,19,22,38 with the majority of published studies identifying a frequency ≤35%.5,16,21,23,25,36,37,39 In contrast to the acetabular index, we did observe that increased age at the time of CR predicted a higher rate of further corrective surgery, which is consistent with Luhmann et al’s37 observation that delaying CR may increase the need for later intervention.

tudies identifying a frequency ≤35%.5,16,21,23,25,36,37,39 In contrast to the acetabular index, we did observe that increased age at the time of CR predicted a higher rate of further corrective surgery, which is consistent with Luhmann et al’s37 observation that delaying CR may increase the need for later intervention. This study has a number of limitations. First, longer follow-up may lead to different values for AVN, acetabular dysplasia, and further corrective surgery. The purpose of this study was to report early results from a prospective cohort of infants undergoing CR. Certainly, we aim to follow this cohort longitudinally to provide long-term success and complication rates. Second, AVN is difficult to unilaterally define, as there are a variety of different classification systems in use across the literature. Given the potential for these variations to impact the reported frequency of AVN within our database, we chose to retrospectively assess AVN using a blinded panel of surgeons each applying the Salter criteria in a yes/no manner, a step the authors felt was imperative to improve the accuracy and consistency of our findings. Third, due to the large number of surgeons contributing to the database, there is considerable variation in treatment practices. Regardless, the authors view this heterogeneity as a strength in that it more accurately reflects real-world practice. Fourth, given the smaller number of hips with certain conditions and/or outcomes, the P-values in our tables should be interpreted with caution. Fifth, we did not measure abduction angle in postreduction immobilization, which has been suggested to influence AVN rates,26,40 as practice variation in postoperative imaging and treatment limited the availability of such data. Finally, the quality of our results is dependent on the completeness and accuracy of data reporting by the individual centers, which is a limitation of any multicenter database study.

ggested to influence AVN rates,26,40 as practice variation in postoperative imaging and treatment limited the availability of such data. Finally, the quality of our results is dependent on the completeness and accuracy of data reporting by the individual centers, which is a limitation of any multicenter database study. In conclusion, this prospective, multicenter cohort of infants undergoing CR for DDH demonstrated a 9% failure rate after initially successful reduction and a 25% rate of AVN at early-term follow-up. In this study, older age at the time of CR and longer immobilization in a spica cast were predictive of needing further corrective surgery for residual dysplasia and developing osteonecrosis, respectively. No other patient-specific factors related to history, treatment, or outcome were associated with the future development of either AVN, residual dysplasia, or failed reduction. Further follow-up of this cohort will be necessary to establish accurate long-term success and complication rates following CR for infantile DDH. Supplementary Material SUPPLEMENTARY MATERIAL Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.pedorthopaedics.com. Funding was received from the International Hip Dysplasia Institute for research support and study coordination. The authors declare no conflicts of interest.

The geometric relationship between femoral version and neck-shaft angle is important for understanding the morphology and biomechanics involved in hip function.1 Previous studies by Drs Walker and Goldsmith2 tremendously increased the understanding of the morphological changes seen in the developing fetal hip but did not properly address the difference between apparent measures and actual measurements in the coronal and transverse planes.3 This led to the faulty conclusion that there is no change in coronal alignment during gestation. Liu et al4 emphasizes the difference between apparent and actual measurements in the coronal and transverse planes by differentiating between true neck/shaft angle (tNSA) and apparent neck/shaft angle (aNSA) as well as inclination and version. The tNSA is measured with the femoral neck perpendicular to the viewer. The same applies to inclination. As such, both provide anatomic angles in the coronal and transverse planes, respectively. aNSA and version both present the femoral neck axis obliquely to the viewer (unless version is 0 in the former case and the neck/shaft angle is 90 degrees in the later). This makes it impossible to precisely measure coronal and transverse plane anatomy because the length of the neck will be distorted in these projected views.

d version both present the femoral neck axis obliquely to the viewer (unless version is 0 in the former case and the neck/shaft angle is 90 degrees in the later). This makes it impossible to precisely measure coronal and transverse plane anatomy because the length of the neck will be distorted in these projected views. For example, version is one of the factors that determine hip rotation. However, version cannot be used to represent inclination unless the femoral neck is perpendicular to the femoral shaft (Fig. 1). In any other configuration, the trajectory of the femoral neck out of the transverse plane artificially shortens the projection seen in the transverse plane. Equating version and inclination in such a case would overestimate the inclination. To directly measure inclination, one would have to abduct the femur until the axis of the femoral neck aligned with the transverse plane allowing the full length of the femoral neck to be appreciated (Fig. 2). When schematized, the difference between determining femoral version and femoral inclination involves the angle at which the camera captures the femur such that the version view is exactly parallel to the femoral shaft, whereas the inclination view is directly perpendicular to the femoral neck (Fig. 3). The difference between the 2 views can be appreciated when considering how proximal femoral landmarks appear on these views as depicted by the numbers also in Figure 3. Such a correction is of clinical importance in guiding surgeons on how much to “drop the hand” in the dorsal/ventral direction when placing hardware into the femoral neck.

en the 2 views can be appreciated when considering how proximal femoral landmarks appear on these views as depicted by the numbers also in Figure 3. Such a correction is of clinical importance in guiding surgeons on how much to “drop the hand” in the dorsal/ventral direction when placing hardware into the femoral neck. FIGURE 1 As it appears in Liu et al, (A) demonstrates 2 femurs and the positioning of the viewer to measure version on a transverse plane perpendicular to the long axis of the femur. B, Version measured in the transverse plane with one line parallel to the bicondylar plane and the other parallel to the femoral neck axis. FIGURE 2 As it appears in Liu et al, (A) demonstrates 2 femurs abducted until the femoral neck axis lies entirely in the transverse plane. B, The inclination measured as the angle between the bicondylar plane and the femoral neck axis. Because the viewpoint is adjusted so that length of the femoral neck is fully appreciated, inclination is not affected by the neck-shaft angle. aNSA indicates apparent neck/shaft angle. FIGURE 3 A schematic representation of the difference in measuring femoral version and femoral inclination. Landmarks in the proximal femur including the femoral head (1), femoral neck (2), greater trochanter (3), and femoral shaft (4) are annotated on all views presented. Left—inclination view: the shaft of the femur is abducted until the femoral neck is perpendicular to the viewer. Right—version view: the shaft of femur is parallel to the beam of the camera, so it is invisible to the viewer. The femoral neck is oblique to the viewer.

oral shaft (4) are annotated on all views presented. Left—inclination view: the shaft of the femur is abducted until the femoral neck is perpendicular to the viewer. Right—version view: the shaft of femur is parallel to the beam of the camera, so it is invisible to the viewer. The femoral neck is oblique to the viewer. As regards neck-shaft angles, aNSA is affected by version. Ideally, the femoral neck-shaft angle would be measured with the axes of the femoral shaft and neck in the coronal plane, describing a femur with 0 degrees of version. As version increases, the projected length of the femoral neck is shortened leading to an increase in the projected neck-shaft angle. For the purposes of discussion, neck-shaft angle measured off the coronal projection of the femur will be called the “apparent” NSA while the angle corrected for version will be called the “true” NSA (Fig. 4). FIGURE 4 As it appears in Liu et al, (A) demonstrates 2 femurs resting in the anatomic position. The apparent neck-shaft angle is measured in the coronal plane. B, Rotates the femurs so that the femoral neck is fully in the coronal plane. Because the femurs are rotated in this manner, version is eliminated. The full length of the femoral neck is appreciated and it is possible to measure the true neck-shaft angle directly.

rent neck-shaft angle is measured in the coronal plane. B, Rotates the femurs so that the femoral neck is fully in the coronal plane. Because the femurs are rotated in this manner, version is eliminated. The full length of the femoral neck is appreciated and it is possible to measure the true neck-shaft angle directly. The relationship between inclination, version, aNSA, and tNSA have been investigated in the setting of femoral derotation osteotomies4 but have not been previously described in the literature with regard to morphology of the developing fetal hip. We will reinterpret the classic work of Walker and Goldsmith by accounting for version, inclination, aNSA, and tNSA. In this way, we can describe both the apparent as well as the actual, anatomic relationships seen during gestation.

usly described in the literature with regard to morphology of the developing fetal hip. We will reinterpret the classic work of Walker and Goldsmith by accounting for version, inclination, aNSA, and tNSA. In this way, we can describe both the apparent as well as the actual, anatomic relationships seen during gestation. METHODS Walker and Goldsmith, in their paper entitled “Morphometric study of the fetal development of the human hip joint2,” acquired 140 fetuses (66 male, 74 female) from the Pathology and Anatomy Departments in Canada and the United States that were the products of elective abortions (62.2%), stillbirths (23.7%), or death during the perinatal period (14.1%). Their specimens ranged from 12 to 42 weeks of age and had no evidence of malformation, minimal maceration, and normal hip morphology by gross examination and under ×10 magnification. In their analysis of age on the developing hip, they measured femoral torsion and the aNSAs of developing femurs with 9 and 10 representative specimens shown in figures 10 and 11 of their paper respectively (Fig. 5). All femurs shown in those figures were right femurs. Femoral version and aNSAs of the specimens that are shown in those 2 figures were measured twice by 4 investigators ranging from medical student to attending. Note that the full set of specimens were not used, instead the study focused on the representative images provided. Inclination and tNSAs were calculated by mathematically manipulating formulas as outlined by Liu and colleagues:

2 figures were measured twice by 4 investigators ranging from medical student to attending. Note that the full set of specimens were not used, instead the study focused on the representative images provided. Inclination and tNSAs were calculated by mathematically manipulating formulas as outlined by Liu and colleagues: FIGURE 5 Walker and Goldsmith’s representative sample of developing fetal femoral version and neck-shaft angle. From Walker and Goldsmith,2 with permission from the Yale Journal of Biology and Medicine. Changes in version, inclination, aNSAs, and tNSAs over time were analyzed by Student t test with α=0.05. Interobserver and intraobserver reliability was determined by Pearson’s R coefficient. RESULTS In congruity with previous work by Walker and Goldsmith, aNSA did not significantly change over development [95% confidence interval (CI), −1.83 to 3.33 degrees, P=0.59] while version increased by an average of 40 degrees (95% CI, +36.57 to +44.93 degrees, P<0.001). However, the tNSA significantly decreased over time by an average of −7.5 degrees (95% CI, −10.20 to −4.58 degrees, P=0.002) and the inclination increased by an average of 32 degrees (95% CI +30.57 to 33.72 degrees, P<0.001). The interobserver Pearson coefficient R=0.98 and the intraobserver Pearson coefficient R=0.99.

However, the tNSA significantly decreased over time by an average of −7.5 degrees (95% CI, −10.20 to −4.58 degrees, P=0.002) and the inclination increased by an average of 32 degrees (95% CI +30.57 to 33.72 degrees, P<0.001). The interobserver Pearson coefficient R=0.98 and the intraobserver Pearson coefficient R=0.99. DISCUSSION The purpose of this study was to elaborate on the findings of Walker and Goldsmith with regard to the morphology of the developing fetal hip. To better understand the changes in the developing joint, one must consider the 3-dimensional relationships between femoral version, inclination, and neck-shaft angle and how such relations are traditionally not fully accounted for when directly measuring off of transverse or coronal projections of the femur on standard radiographs with the femur in the anatomic position.

nt, one must consider the 3-dimensional relationships between femoral version, inclination, and neck-shaft angle and how such relations are traditionally not fully accounted for when directly measuring off of transverse or coronal projections of the femur on standard radiographs with the femur in the anatomic position. Version should not be used as a substitute for inclination unless the femoral neck and shaft are perpendicular, placing the femoral neck fully in the transverse plane. Any deviation of the femoral neck out of the transverse plane in the superior or inferior direction would lead to a shortening of the projection of the femoral neck in the transverse plane and an overestimation of inclination. Readers who have not previously been introduced to this concept may benefit from an in-depth review of Liu et al4 where these concepts are presented in detail. In addition, the direct measurement of the neck-shaft angle on a radiograph is most likely an overestimation of the actual neck-shaft angle. As version increases, the projection of the femoral neck in the coronal plane is also shortened leading to an increase in the aNSA, therefore overestimating tNSA.

ented in detail. In addition, the direct measurement of the neck-shaft angle on a radiograph is most likely an overestimation of the actual neck-shaft angle. As version increases, the projection of the femoral neck in the coronal plane is also shortened leading to an increase in the aNSA, therefore overestimating tNSA. After accounting for these spatial relationships, we examined the representative developing fetal femurs displayed in Walker and Goldsmith’s study. Our findings are consistent with theirs with respect to a significant increase in version and no significant change in aNSA during fetal development. Elaborating on their findings, we concluded that the 40 degrees change in version in the presence of no change in the aNSA is comprised of a significant −7.5 degrees change in tNSA and a +32 degrees change in inclination. When interobserver and intraobserver observations were plotted against each other, the Pearson Coefficients were R=0.98 and 0.99, respectively, indicating this set of observations was reliable among different observers and repeat observations. One potential weakness of the study is that only a selected sample rather than the full set of specimens were measured; however, the extremely high degree of correlation as well as the small SDs reported in the original paper suggest that additional measurements would closely replicate the findings detailed here.

ions. One potential weakness of the study is that only a selected sample rather than the full set of specimens were measured; however, the extremely high degree of correlation as well as the small SDs reported in the original paper suggest that additional measurements would closely replicate the findings detailed here. In conclusion, Walker and Goldsmith made classic observations concerning changes in hip morphology from 12 weeks of gestational age to term. They demonstrated changes in both the coronal and transverse morphology of the femur over time, but the existence of that reality and its extent are lost on a reader who is not well versed in the difference between aNSA and tNSA, version and inclination. These 4 concepts are useful for tracking anatomic as well as apparent changes in the shape of the developing hip joint.5–7 The authors declare no conflicts of interest.