Hopes, concerns, satisfaction and regret in a precision medicine trial for childhood cancer: a mixed-methods study of parent and patient perspectives.

BACKGROUND: Paediatric precision oncology aims to match therapeutic agents to driver gene targets. We investigated whether parents and patients regret participation in precision medicine trials, particularly when their hopes are unfulfilled. METHODS: Parents and adolescent patients completed questionnaires at trial enrolment (T0) and after receiving results (T1). Parents opted-in to an interview at T1. Bereaved parents completed a questionnaire 6-months post-bereavement (T1B). We analysed quantitative data with R and qualitative data thematically with NVivo, before integrating all data for interpretation. RESULTS: 182 parents and 23 patients completed T0; 108/182 parents and 8/23 patients completed T1; 27/98 bereaved parents completed T1B; and 45/108 parents were interviewed. At enrolment, participants held concurrent hopes that precision medicine would benefit future children and their child. Participants expressed concern regarding wait-times for receipt of results. Most participants found the trial beneficial and not burdensome, including bereaved parents. Participants reported high trial satisfaction (median scores: parents: 93/100; patients: 80/100). Participants expressed few regrets (parent median scores: parents: 10/100; bereaved parents: 15/100; patient regret: 2/8 expressed minimal regret). CONCLUSIONS: Even when trial outcomes did not match their hopes, parents and patients rarely regretted participating in a childhood cancer precision medicine trial. These data are critical for integrating participants' views into future precision medicine delivery.

Slipped Capital Femoral Epiphysis in Children without Obesity.

OBJECTIVE: To evaluate rates and characteristics of slipped capital femoral epiphysis (SCFE) in children who are not obese to prevent missed diagnoses and subsequent complications. STUDY DESIGN: A multicenter, retrospective review identified all patients with SCFE from January 1, 2003 to December 31, 2012. Patients were excluded if they received previous surgery at an outside institution, had no recorded height and weight, or had medical co-morbidity associated with increased risk of SCFE. Body mass index (BMI) percentile for age was calculated and categorized for each patient (patients without obesity vs with obesity). RESULTS: In total, 275 patients met inclusion criteria. Average BMI was 91.2 percentile (range: 8.4-99.7). Thirteen percent (34 patients) were considered "normal weight" (BMI 5%-85%), 17% (48 patients) were considered "overweight" (BMI 85%- 95%), and 70% (193 patients) were considered "obese" (BMI >95%). Average BMI percentile was higher in male than female patients (93.2 ± 12.7 vs 88.5 ± 21.4, P = .034). Patients without obesity were older compared with patients with obesity (12.2 ± 1.7 vs 11.7 ± 1.6 years, P = .015). Fewer patients without obesity were seen at the hospital in the southwest. The southwest had fewer patients without obesity than the northeast (18.3% vs 36.1%, P = .002). Patients without obesity were more likely to present with a severe slip as graded by Wilson percent displacement (27.2% vs 11.4%, P = .007) and an unstable slip (32.9% vs 14.7%, P = .001). CONCLUSION: Rates of nonobese SCFE in this study are higher than reported in the previous literature. Normal weight patients with SCFE are more likely to be older, female, and present with a severe and unstable SCFE.

Responses to a cancer diagnosis: a qualitative patient-centred interview study.

PURPOSE: A cancer diagnosis is an emotive and challenging time for patients. This study aimed to systematically explore patients' accounts of experiencing their cancer diagnosis. The purpose of this article is to offer a typology of patient responses to receiving a cancer diagnosis as a means through which to affirm the range of patients' experiences and to guide clinicians' practice. METHODS: Qualitative semi-structured interviews were conducted between 2015 and 2017 with 80 patients living with cancer: 34 females and 46 males, aged between 31 and 85, diagnosed with a range of cancer types, stages and treatment trajectories, from two metropolitan hospitals on the east coast of Australia. Interview data were analysed thematically, using the framework approach. RESULTS: A typology of responses to the cancer diagnosis was derived from the analysis and included (1) the incongruent diagnosis, unexpected because it did not 'fit' with the patient's 'healthy' identity; (2) the incidental diagnosis, arising from seemingly unrelated or minor medical investigations; (3) the validating diagnosis, as explanation and confirmation of previously unexplained symptoms, pain or feelings; (4) the life context diagnosis, where the cancer diagnosis was positioned relative to other challenging life events, or as relatively inconsequential compared with the hardship of others. CONCLUSIONS: A diagnosis of cancer is not always (or only) experienced by patients with shock and despair. Diagnosis is perceived and experienced in diverse ways, shaped by broader social or life contexts, and with important implications for the clinical encounter and communication from an oncology perspective.

Pediatric Femoral Shaft Fractures: A Multicenter Review of the AAOS Clinical Practice Guidelines Before and After 2009.

BACKGROUND: To determine if the AAOS clinical practice guidelines (CPG) for the treatment of pediatric femoral shaft fractures (2009) changed treatment, we analyzed pediatric femoral shaft fractures at 4 high-volume, geographically separated, level-1 pediatric trauma centers over a 10-year period (2004 to 2013). METHODS: Consecutive series of pediatric femoral shaft fractures (ages, birth to 18 y) treated at the 4 centers were reviewed. Treatment methods were analyzed by age and treatment method for each center and in aggregate. RESULTS: Of 2646 fractures, 1476 (55.8%) were treated nonoperatively and 1170 fractures operatively. Of the operative group, flexible intramedullary nails (IMN) were used for 568 patients (21.5%), locked intramedullary nails (LIMNs) for 309 (11.7%), and plating for 188 (7.1%). In total, 105 fractures were treated with external fixation or skeletal traction. Analysis before and after the CPG publication revealed a significant increase in the use of interlocked IMNs in patients younger than 11 years (0.5% before, 3.8% after; P<0.001). Over the same time period there was an increase in surgical management, regardless of technique, for patients younger than 5 years (6.4% before, 8.4% after; P=0.206). There were considerable differences in treatment among centers: 74% of fractures treated with plating were from a single center (center A), which also contributed 68% of patients younger than 5 years treated with plating; center B had the highest rate (41%) of flexible IMN in children younger than 5 years; center C had the highest rate (63%) of LIMN in children younger than 11 years; and center D treated the fewest patients outside the CPG guidelines. CONCLUSIONS: Following publication of the AAOS CPG, there was a significant increase in the use of LIMNs in patients younger than 11 years old and a trend toward surgical treatment in patients younger than 5 years. The considerable variability among centers in treatment methods and adherence to the CPG highlights the need for further outcome studies to better define optimal treatment methods and perhaps update the AAOS CPG guidelines. LEVEL OF EVIDENCE: Level III-therapeutic.

Pulseless Supracondylar Humerus Fracture With Anterior Interosseous Nerve or Median Nerve Injury-An Absolute Indication for Open Reduction?

BACKGROUND: Optimal management for a pulseless supracondylar humerus fracture associated with anterior interosseous nerve (AIN) or median nerve injury is unclear. The purpose of this study was to determine the incidence of pulseless supracondylar humerus fractures associated with AIN or median nerve injury, to assess open versus closed surgical management, to determine factors associated with the need for neurovascular intervention, and to report the outcome. METHODS: A retrospective review was performed at 4 pediatric trauma hospitals on all patients who sustained a Gartland III or IV supracondylar humerus fracture with the combination of absent distal palpable pulses and AIN or median nerve injury between 2000 and 2014. Choice of treatment, details regarding preoperative and postoperative exam findings, follow-up course, and outcome were recorded. RESULTS: A total of 71 patients met inclusion criteria; 52 patients (73%) underwent closed reduction (CR); 19 patients (27%) underwent open reduction (OR) and early antecubital fossa exploration. The index procedure of CR plus percutaneous pinning was sufficient treatment in 50 (of 52, 96%) patients with only 2 requiring reoperation. One patient developed compartment syndrome approximately 9 hours after CRPP (13.5 h after time of injury) and underwent emergent fasciotomies. Of the 19 patients who underwent OR and early exploration, 6 needed vascular procedures, 5 required detethering of entrapped surrounding fibrous tissues. Forty patients were diagnosed with median nerve palsy versus 31 diagnosed with AIN palsy. There was no significant difference between patients presenting with median nerve versus AIN palsy, with similar rates of need for OR (10/40; 25% vs. 9/31; 29%), rate of compartment syndrome (3/40; 7.5% vs. 3/31; 9.7%), need for reoperation (4/40; 10% vs. 6.5%), and ultimate resolution of nerve palsy (4/36; 20.1% vs. 3/30; 10%). Compartment syndrome developed in 6 (of 71, 8.5%) patients and was associated with poor perfusion status on presentation and delayed time from injury to surgery. In patients with at least 3-month neurological follow-up, 59 (of 61, 97%) patients had complete resolution of nerve palsy. CONCLUSIONS: Although previous authors have suggested a pulseless SCH fx with an associated AIN or median nerve injury should be treated with exploration and OR, 70% (50/71) of the patients in this series were treated with a CR. In this series, both AIN and median nerve palsies among patients presenting with pulseless extremity and Gartland III or IV SCH fracture, offer similar rates of OR, risk of compartment syndrome, and resolution of nerve palsy. LEVEL OF EVIDENCE: Level IV.

Incidence, Risk Factors, and Definition for Nonunion in Pediatric Lateral Condyle Fractures.

INTRODUCTION: Lateral condyle fractures are a common pediatric elbow injury. Nonunion is a known complication of this injury but its incidence and causative risk factors are unknown. Further, a clear and consistent definition of nonunion for pediatric lateral condyle fractures does not exist. The purpose of this study is to determine the rate of nonunion, the risk factors associated with it and to provide a clear definition. METHODS: A retrospective chart review of all pediatric lateral condyle fractures treated at an urban, tertiary pediatric care center between 2001 and 2014. Data collected included demographics, Weiss classification, type of treatment, follow-up, time from injury to surgery and complications. For patients with nonunions, additional treatments and final range of motion were also recorded. A nonunion was defined as lack of callus with fragment migration by 8 weeks after initiation of treatment. RESULTS: A total of 530 patients were identified of which 500 were available for review. There were 7/500 (1.4%) nonunions in the cohort. Nonunion occurred in 1.4% (2/140) of type I fractures, 0% (0 /178) of type II fractures, and 3% (5/168) of type III fractures. The only significant risk factor for nonunion was the presence of a type III fracture (P=0.05). Five patients with nonunion underwent revision surgery with a partially threaded cannulated cancellous screw. All of these patients went on to union. Four of the 5 patients had their screws removed after union. CONCLUSION: Nonunion after pediatric lateral condyle fracture is rare and is defined by lack of any callus with fragment migration at 8 weeks. The only significant risk factor for nonunion development was the presence of a type III fracture. Revision surgery with a partially threaded screw achieved union in all cases. LEVEL OF EVIDENCE: Level IV-retrospective case review.

Continuing Delay in the Diagnosis of Slipped Capital Femoral Epiphysis.

OBJECTIVE: To evaluate whether the time from symptom onset to diagnosis of slipped capital femoral epiphysis (SCFE) has improved over a recent decade compared with reports of previous decades. STUDY DESIGN: Retrospective review of 481 patients admitted with a diagnosis of SCFE at three large pediatric hospitals between January 2003 and December 2012. RESULTS: The average time from symptom onset to diagnosis of SCFE was 17 weeks (range, 0-to 169). There were no significant differences in time from symptom onset to diagnosis across 2-year intervals of the 10-year study period (P = .94). The time from evaluation by first provider to diagnosis was significantly shorter for patients evaluated at an orthopedic clinic (mean, 0 weeks; range, 0-0 weeks) compared with patients evaluated by a primary care provider (mean, 4 weeks; range, 0-52 weeks; r = 0.24; P = .003) or at an emergency department (mean, 6 weeks, range, 0-104 weeks; r = 0.36; P = .008). Fifty-two patients (10.8%) developed a second SCFE after treatment of the first affected side. The time from the onset of symptoms to diagnosis for the second episode of SCFE was significantly shorter (r = 0.19; P < .001), with mean interval of 11 weeks (range, 0-104 weeks) from symptom onset to diagnosis. There were significantly more cases of mildly severe SCFE, as defined by the Wilson classification scheme, in second episodes of SCFE compared with first episodes of SCFE (OR, 4.44; P = .001). CONCLUSION: Despite reports documenting a lag in time to the diagnosis of SCFE more than a decade ago, there has been no improvement in the speed of diagnosis. Decreases in both the time to diagnosis and the severity of findings for the second episode of SCFE suggest that the education of at-risk children and their families (or providers) may be of benefit in decreasing this delay.

Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis.

BACKGROUND: When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis. OBJECTIVE: To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis. MATERIALS AND METHODS: Using multiplanar imaging techniques, measures of vertebral cross-sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight. RESULTS: Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 ± 0.81 vs. 7.40 ± 0.99 cm(2); P = 0.0007) and 13.9% (8.22 ± 0.84 vs. 9.55 ± 1.61 cm(2); P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 ± 0.85 vs. 7.31 ± 0.62 mm and 9.09 ± 0.87 vs. 7.61 ± 1.00 mm for girls and boys respectively; both P ≤ 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index. CONCLUSION: We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights - two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis.

Do Age and Weightbearing Radiographs Affect Lateral Joint Space and Fibular Height Measurements in Patients With Discoid Lateral Meniscus?

BACKGROUND: Several radiographic parameters have been associated with a discoid lateral meniscus. However, limited information is available regarding the radiographic findings of a discoid meniscus in the pediatric population. PURPOSE: To determine the effect of age and weightbearing (WB) on radiographic parameters associated with discoid lateral menisci in pediatric patients. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Radiographs of pediatric patients with arthroscopically confirmed lateral discoid menisci were compared with age-, side-, and sex-matched individuals with confirmed normal menisci. Radiographic parameters of lateral joint space width (LJSW) and fibular head height (FHH) were measured by 3 physicians. RESULTS: Significant differences were found between the discoid and control groups when LJSW (P = .002) and FHH (P < .001) were compared. Interrater reliability was good for LJSW (intraclass correlation coefficient [ICC], 0.635) and excellent for FHH (ICC, 0.759). WB radiographs were noted to have better interrater reliability compared with non-WB radiographs for LJSW (ICC, 0.729 vs 0.514, respectively) but had reduced interrater reliability for FHH (ICC, 0.625 vs 0.868, respectively). Subgroup analysis with age stratification indicated that FHH was significantly decreased (indicative of a high fibular head) in the discoid group for all age groups (P < .001 for <10 years and 10-14 years; P = .030 for >14 years); however, LJSW was significantly different only in patients older than 14 years. CONCLUSION: Increased LJSW and FHH were associated with discoid lateral menisci and showed satisfactory interrater reliability. Radiographic evaluation for potential discoid meniscus in pediatric and adolescent patients may be improved by use of fibular height to indicate the presence of a discoid lateral meniscus across age groups, while lateral joint space may be more reliable for older patients.

Preventing Distal Junctional Kyphosis by Applying the Stable Sagittal Vertebra Concept to Selective Thoracic Fusion in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Multicenter retrospective review. OBJECTIVE: To assess the effectiveness of using the stable sagittal vertebra (SSV) for selecting the lowest instrumented vertebrae (LIV) to prevent distal junctional kyphosis (DJK) in selective thoracic fusions. SUMMARY OF BACKGROUND DATA: Cho et al. reported that including the SSV in a fusion decreased the rate of DJK in thoracic hyperkyphosis. METHODS: A retrospective review was performed of patients from two pediatric hospitals with adolescent idiopathic scoliosis who underwent selective posterior thoracic fusion with the LIV at L2 or above from 2000 to 2012. Patients with less than 2 years' follow-up were excluded. The primary outcome measure was DJK, defined radiographically as ≥10° between the superior end plate of the LIV and the inferior end plate of the vertebra below on a standing lateral radiograph. We investigated the SSV, which was defined as the vertebral level at which 50% of the vertebral body was in front of the posterior sacral vertical line (PSVL) on a standing lateral radiograph. This particular definition was referred to as SSV. RESULTS: A total of 113 patients met the inclusion criteria. Mean age was 14.4 years. Mean Cobb angle was 58°. The overall rate of DJK was 7% (8/113). When the LIV was superior to SSV, the rate of DJK was 17% (8/46) versus 0% (0/67) when the LIV was at or inferior to SSV (p=.01). The rates of DJK for patients with the LIV one, two, and three levels above SSV were 17% (4/24), 7% (1/14), and 43% (3/7), respectively. There was no significant association between preoperative or postoperative maximum kyphosis, thoracic kyphosis, thoracolumbar kyphosis, pelvic incidence, sagittal balance or coronal balance, and development of DJK. CONCLUSION: Although LIV selection is complex, choosing the LIV at or below the SSV is a simple rule that minimizes the risk of DJK. LEVEL OF EVIDENCE: Level IV.

Antibiotic optimisation in 'the bush': Local know-how and core-periphery relations.

The growing global concern around antimicrobial mis-use and proliferating resistance has resulted in increasing interest in optimising antibiotics, particularly in hospitals. While the agenda to tighten antibiotic use has been critically explored in metropolitan settings, the dynamics of rural and remote settings have remained largely unexplored. Drawing on 30 interviews with doctors, nurses, and pharmacists in a remote Australian hospital, we focus on the pertinence of setting, and its importance for contextualising and potentially achieving antibiotic optimisation. Building on previous work on the dynamics of locale and core-periphery relations, here we consider how antimicrobial practice is deeply embedded in experiences of being on the geographical periphery, and crucially, at the periphery of (established) knowledge.

Compartment syndrome in infants and toddlers.

PURPOSE: To study the cause, diagnosis, treatment and outcome of acute compartment syndrome in infants and toddlers aged <3 years. METHODS: Fifteen patients aged <3 years with acute compartment syndrome were identified from two large pediatric trauma centers over a fifteen-year period. All children underwent fasciotomy. The mechanism of injury, time of injury, time to diagnosis, compartment pressures, time to fasciotomy, and outcome at the time of the latest follow-up were recorded. RESULTS: Nine (60 %) of fifteen patients developed compartment syndrome secondary to trauma, four (4/15, 27 %) due to infection, and two (2/15, 13 %) due to intravenous infiltration. The average time from injury or hospital admission to fasciotomy was 31.8 h (range 2.9-136.3 h). In general, the functional outcome was excellent at the latest follow-up with thirteen (13/15, 87 %) patients having an excellent outcome. No cases of Volkmann's ischemia were noted at the time of fasciotomy, even when performed as late as 5 days after injury. CONCLUSIONS: Compared to the general pediatric population, the diagnosis of compartment syndrome in infants and toddlers may be further delayed, i.e., >24 h after injury. Despite delays in diagnosis and time to treatment, the present study shows that outcomes in infants and toddlers remain favorable even when fasciotomy is performed 48-72 h after injury. LEVEL OF EVIDENCE: Case series, level IV.

Removal of Infected Posterior Spinal Implants: Be Prepared to Transfuse.

STUDY DESIGN: Single-center retrospective review of spinal deformity patients undergoing removal of infected posterior spinal fusion implants over a 10-year period. OBJECTIVE: To evaluate the intraoperative blood loss and perioperative complications of implant removal in posterior spinal fusions. SUMMARY OF BACKGROUND DATA: To our knowledge, no studies examine blood loss or complications associated with removal of infected spinal implants in spinal deformity. METHODS: A retrospective review of 28 consecutive cases of infected posterior spinal fusion implant removal from 2003 to 2012 was performed. Exclusion criteria were patients with ≤6 levels of instrumentation, a partial removal of implants or a bleeding disorder. RESULTS: The average estimated blood loss was 465 mL (range 100-1,505 mL). Average estimated blood volume was 3,814 mL (range 1,840-9,264 mL). The average percentage of estimated blood loss was 14.2% (range 1.9%-43.5%). On postoperative labs obtained at the conclusion of the procedure, there was an average loss in hematocrit of 6.6 from preoperative values. Seventy-one percent of patients (20/28) received a blood transfusion; 39% (11/28) of these received a transfusion intraoperatively and 54% (15/28) received a transfusion postoperatively. Forty-six percent of patients (13/28) experienced an associated medical complication in the postoperative period. Among these 13, there were 16 total complications, with the most common being seizures (4/16), pneumonia (2/16), and sepsis (2/16). Average hospital stay was 14 days (range 4-52). CONCLUSION: Seventy-one percent of patients undergoing removal of infected spinal implants received a blood transfusion. We recommend having blood products available when removing posterior spinal instrumentation >6 levels. Patients and families should be counseled on the high risk of complications and expected hospital stay in these cases. LEVEL OF EVIDENCE: Level III.

Culturally and linguistically diverse patient participation in glioma research.

Marginal communities, such as culturally and linguistically diverse (CALD) patients, have significantly lower rates of recruitment, accrual, and retention in cancer clinical trials. A combination of language and cultural barriers means that trial participation from CALD communities remains at suboptimal levels, which in turn favors research findings that are biased towards therapeutic effects or toxicities within the context of non-CALD populations. Here we outline some key challenges and implications for CALD patient participation in glioma research in countries such as Australia, where English is the language of governance and health services implementation. We highlight multistakeholder interventions to improve both investigator recruitment and participation of CALD communities in future glioma research, particularly in this era when global migration has come of age. Enhancing research participation of CALD communities ensures not only wider understanding of genetic heterogeneity to improve glioma outcomes but also equity in access to care.