Participant Diversity in United States Randomized Controlled Trials of Antibacterials for Staphylococcus aureus Infections, 2000-2021.

BACKGROUND: Equitable representation of members from historically marginalized groups is important in clinical trials, which inform standards of care. The goal of this study was to characterize the demographics and proportional subgroup reporting and representation of participants enrolled in randomized controlled trials (RCTs) of antibacterials used to treat Staphylococcus aureus infections. METHODS: We examined randomized controlled registrational and strategy trials published from 2000-2021 to determine the sex, race, and ethnicity of participants. Participation to incidence ratios (PIRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the disease population in each group. Underrepresentation was defined as a PIR <0.8. RESULTS: Of the 87 included studies, 82 (94.2%) reported participant sex; 69 (79.3%) reported participant race; and 20 (23.0%) included ethnicity data. Only 17 (19.5%) studies enrolled American Indian/Alaskan Native participants. Median PIRs indicated that Asian and Black participants were underrepresented in RCTs compared with the incidence of methicillin-resistant S. aureus (MRSA) infections in these subgroups. Underrepresentation of Black participants was associated with a larger study size, international sites, industry sponsorship, and Phase 2/3 trials compared with Phase 4 trials (P<0.05 for each). Black participants had over 4 times the odds of being underrepresented in Phase 2/3 trials compared with Phase 4 trials (OR 4.57; 95% CI 1.14-18.3). CONCLUSIONS: Standardized reporting methods for race and ethnicity and efforts to increase recruitment of marginalized groups would help ensure equity, rigor, and generalizability in RCTs of antibacterial agents and reduce health inequities.

Intrarater and Interrater Reliability of Radiographic Characteristics in Skeletally Immature Patients With Anterior Cruciate Ligament Tears: A PLUTO Study Group Reliability Study.

BACKGROUND: Radiographic measurements of limb alignment in skeletally immature patients with anterior cruciate ligament (ACL) tears are frequently used for surgical decision-making, preoperative planning, and postoperative monitoring of skeletal growth. However, the interrater and intrarater reliability of these radiographic characteristics in this patient population is not well documented. HYPOTHESIS: Excellent reliability across 4 raters will be demonstrated for all digital measures of length, coronal plane joint orientation angles, mechanical axis, and tibial slope in skeletally immature patients with ACL tears. STUDY DESIGN: Cohort study (diagnosis). METHODS: Three fellowship-trained orthopaedic surgeons and 1 medical student performed 2 rounds of radiographic measurements on digital imaging (lateral knee radiographs and long-leg radiographs) of skeletally immature patients with ACL tears. Intrarater and interrater reliability for continuous radiographic measurements was assessed with intraclass correlation coefficients (ICCs) across 4 raters with 95% CIs for affected and unaffected side measurements. Interrater reliability analysis used an ICC (2, 4) structure and intrarater reliability analysis used an ICC (2, 1) structure. A weighted kappa coefficient was calculated for ordinal variables along with 95% CIs for both interrater and intrarater reliability. Agreement statistic interpretations are based on scales described by Fleiss, and Cicchetti and Sparrow: <0.40, poor; 0.40 to 0.59, fair; 0.60 to 0.74, good; and >0.74, excellent. RESULTS: Radiographs from a convenience sample of 43 patients were included. Intrarater reliability was excellent for nearly all measurements and raters. Interrater reliability was also excellent for nearly all reads for all measurements. CONCLUSION: Radiographic reliability of long-leg radiographs and lateral knee x-rays in skeletally immature children with ACL tears is excellent across nearly all measures and raters and can be obtained and interpreted as reliable and reproducible means to measure limb length and alignment. LEVEL OF EVIDENCE: Level III.

Assessment of Skeletal Maturity and Postoperative Growth Disturbance After Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients: A Systematic Review.

BACKGROUND: Growth disturbance is an uncommon but potentially serious complication after anterior cruciate ligament (ACL) reconstruction in skeletally immature patients. PURPOSE: To describe how the pediatric ACL literature has assessed preoperative skeletal maturity and the amount of growth remaining and to comprehensively review the incidence, reporting, and monitoring of postoperative growth disturbance. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: This review included studies reporting original research of clinical outcomes of skeletally immature patients after ACL reconstruction. Patient characteristics, surgical techniques, preoperative assessments of skeletal maturity or growth remaining, and postoperative assessments of growth disturbances were extracted. RESULTS: A total of 100 studies met inclusion criteria. All studies reported chronological age, and 28 studies (28%) assessed skeletal age. A total of 44 studies (44%) used Tanner staging, and 12 studies (12%) obtained standing hip-to-ankle radiographs preoperatively. In total, 42 patients (2.1%) demonstrated a leg length discrepancy (LLD) >10 mm postoperatively, including 9 patients (0.5%) with LLD >20 mm; furthermore, 11 patients (0.6%) with LLD underwent growth modulation. Shortening was the most common deformity overall, but overgrowth was reported more frequently in patients who had undergone all-epiphyseal techniques. Most LLDs involved the femur (83%). A total of 26 patients (1.3%) demonstrated a postoperative angular deformity ≥5°, and 9 of these patients underwent growth modulation. The most common deformities were femoral valgus (41%), tibial recurvatum (33%), and tibial varus (22%). Although standing hip-to-ankle radiographs were the most common radiographic assessment of growth disturbance, most studies inadequately reported the clinical and radiographic methods of assessment for growth disturbance. Additionally, only 35% of studies explicitly followed patients to skeletal maturity. CONCLUSION: This systematic review described significant variability in the reporting and monitoring of growth-related complications after ACL reconstruction in skeletally immature patients. The incidence of LLD and angular deformity appeared to be low, but the quality of research was not comprehensive enough for accurate assessment. REGISTRATION: CRD42019136059 (PROSPERO).

Prevalence, Patterns, and Cost of Care for Children with Cerebral Palsy Enrolled in Medicaid Managed Care.

BACKGROUND: In the United States, many children with cerebral palsy (CP) obtain health care coverage through managed Medicaid, but little is known about the current demographics or management of this high-need, complex population. OBJECTIVE: To develop U.S. population-level information about the prevalence of CP, management patterns, and costs. METHODS: Data (2013-2015) were analyzed from a managed Medicaid database with coverage of children and adolescents in 15 states. Analyses included demographic information and use of 10 prespecified CP management options often used to manage spasticity. Code-based algorithms were applied to indicate presence of spasticity and determine the likely ambulatory status. RESULTS: In this claims analysis, the prevalence estimate of CP was 1.78 per 1,000 patients. Most (69.8%) children with CP had spasticity, of which 20.8% had hemiplegia, 15.6% diplegia, 32.9% quadriplegia, and 30.5% CP unspecified. Overall, 42.4% of children with CP were not treated with any of the 10 CP management options via Medicaid. Among treated children, the most common management options were physical therapy (37.1%), orthotics (29.9%), oral baclofen (13.5%) and botulinum toxins (9.4%). Overall annualized Medicaid costs were higher for children with CP versus children in the overall database population ($22,383 vs. $1,358). Within the CP population, costs were higher for those children who were likely nonambulatory than for those who were likely ambulatory ($43,687 vs. $10,368, respectively). CONCLUSIONS: Most children with CP have spasticity, and the costs of care are high. This study highlights wide variation in the way CP is managed, with many young patients not receiving CP management options via Medicaid. DISCLOSURES: This analysis was funded by Ipsen Biopharmaceuticals and conducted by Milliman. Pulgar and Bains were employees of Ipsen Biopharmaceuticals during the conduct of this study. Chambers is a consultant for OrthoPediatrics and an employee of the University of California. Pyenson and Ferro are employees of Milliman, as was Sawhney during the analysis. Gooch, Noritz, and Wright report no conflicts of interest. Part of this work was presented as a poster at TOXINS 2017: Basic Science and Clinical Aspects of Botulinum and Other Neurotoxins, held January 18-21, 2017, in Madrid, Spain.

Antibacterial resistance leadership group: open for business.

Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.

An epidemic of methicillin-resistant Staphylococcus aureus soft tissue infections among medically underserved patients.

HYPOTHESIS: A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in soft tissue infections presents a treatment challenge. DESIGN: Retrospective analysis. SETTING: The San Francisco General Hospital Integrated Soft Tissue Infection (ISIS) Clinic. PATIENTS: Patients treated at the ISIS Clinic from July 1, 2000, to June 30, 2003. MAIN OUTCOME MEASURES: Information on patient demographics, surgical procedures, microbiologic studies, and antibiotic treatments was obtained for all patients treated in the ISIS Clinic. Microbial data and antibiotic susceptibility pattern of S aureus, treatment outcome, and antibiotic prescribed were analyzed for all evaluable patients. RESULTS: The ISIS Clinic treated 6156 unique patients for 12,012 episodes of infection. In this cohort, 5164 (84%) were either homeless or had no health insurance. More than half of the patients (58%) were injection drug users, but most had only 1 prior visit to the clinic (62%). Patients underwent a surgical procedure 7707 times (64%). Of the 837 positive cultures obtained, S aureus was recovered 695 times (83%), and 525 (63%) of the cultures contained MRSA. Therefore, a full 76% of all S aureus isolated was MRSA. In a subset analysis of 622 cultures collected prospectively from consecutive patients, 282 (45%) grew organisms, of which 256 (91%) were S aureus. MRSA represented 59% of all S aureus isolated. Homelessness and injection drug use were risk factors for infection by S aureus and MRSA. In another subgroup of patients with soft tissue infections that required admission to the hospital, MRSA was recovered from the cultures in 149 patients. In these patients with MRSA, 44 (30%) only received a beta-lactam antibiotic, inactive against MRSA, and had full resolution of their infection. CONCLUSIONS: The prevalence of MRSA soft tissue infections in the medically underserved ISIS Clinic cohort is extremely high. The transmission of the MRSA seems to be in the community. Antibiotic therapy directed at MRSA may not be needed in a large number of patients with these soft tissue infections. Studies to identify the source and cause of this MRSA outbreak are urgently needed. Clinical trials to examine the need for antibiotic therapy in soft tissue infections should be conducted.