The impact of inversions across 33,924 families with rare disease from a national genome sequencing project.

Detection of structural variants (SVs) is currently biased toward those that alter copy number. The relative contribution of inversions toward genetic disease is unclear. In this study, we analyzed genome sequencing data for 33,924 families with rare disease from the 100,000 Genomes Project. From a database hosting >500 million SVs, we focused on 351 genes where haploinsufficiency is a confirmed disease mechanism and identified 47 ultra-rare rearrangements that included an inversion (24 bp to 36.4 Mb, 20/47 de novo). Validation utilized a number of orthogonal approaches, including retrospective exome analysis. RNA-seq data supported the respective diagnoses for six participants. Phenotypic blending was apparent in four probands. Diagnostic odysseys were a common theme (>50 years for one individual), and targeted analysis for the specific gene had already been performed for 30% of these individuals but with no findings. We provide formal confirmation of a European founder origin for an intragenic MSH2 inversion. For two individuals with complex SVs involving the MECP2 mutational hotspot, ambiguous SV structures were resolved using long-read sequencing, influencing clinical interpretation. A de novo inversion of HOXD11-13 was uncovered in a family with Kantaputra-type mesomelic dysplasia. Lastly, a complex translocation disrupting APC and involving nine rearranged segments confirmed a clinical diagnosis for three family members and resolved a conundrum for a sibling with a single polyp. Overall, inversions play a small but notable role in rare disease, likely explaining the etiology in around 1/750 families across heterogeneous clinical cohorts.

Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study.

OBJECTIVE: To determine if patients that develop lingering neurologic symptoms of fatigue and "brain fog" after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology. DESIGN: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function. RESULTS: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion. CONCLUSIONS: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19. (www. CLINICALTRIALS: gov; NCT04860869).

Saturation genome editing of DDX3X clarifies pathogenicity of germline and somatic variation.

Loss-of-function of DDX3X is a leading cause of neurodevelopmental disorders (NDD) in females. DDX3X is also a somatically mutated cancer driver gene proposed to have tumour promoting and suppressing effects. We perform saturation genome editing of DDX3X, testing in vitro the functional impact of 12,776 nucleotide variants. We identify 3432 functionally abnormal variants, in three distinct classes. We train a machine learning classifier to identify functionally abnormal variants of NDD-relevance. This classifier has at least 97% sensitivity and 99% specificity to detect variants pathogenic for NDD, substantially out-performing in silico predictors, and resolving up to 93% of variants of uncertain significance. Moreover, functionally-abnormal variants can account for almost all of the excess nonsynonymous DDX3X somatic mutations seen in DDX3X-driven cancers. Systematic maps of variant effects generated in experimentally tractable cell types have the potential to transform clinical interpretation of both germline and somatic disease-associated variation.

Community Water Fluoridation and Rate of Pediatric Fractures.

BACKGROUND: The effect of community water fluoridation on bone fragility and fracture has been inconclusive in the literature. The null hypothesis of this study was that no association was observed between water fluoride level and risk of fracture in children. METHODS: Community fluoridation data were obtained from the Centers for Disease Control and Prevention while data on fracture rates were obtained from the PearlDiver database. The rate of fracture type for each state was then compared with state-level fluoridation data using Pearson correlation coefficients and Wilcoxon rank-sum tests. RESULTS: Positive correlations were found between the percentage of state water fluoridation and fracture rates for both bone forearm fracture (BBFFx) and femur fracture. Fluoride levels had positive correlations with fracture rates for all fracture types. Increased fracture rates were found between states in the highest quartiles of percentage of state water fluoridation and fluoride water levels for supracondylar humerus fracture and BBFFx. CONCLUSIONS: A higher level of water fluoridation was associated with higher rates of supracondylar humerus fracture and BBFFx in children aged 4 to 10 years. These findings do not imply causality, but they suggest that additional investigation into the effect of fluoride on pediatric bone health may be indicated.

Posterior Fixation Without Debridement for Vertebral Body Osteomyelitis and Discitis: A 10-Year Retrospective Review.

BACKGROUND: Surgical treatment of vertebral osteomyelitis, discitis, and epidural abscesses is indicated in the setting of failure of antibiotic therapy, neurological deficits, epidural abscess, or spinal instability/deformity. Historically, surgical treatment mandated aggressive debridement and spinal stabilization. However, there is growing evidence that direct debridement may not be necessary and may contribute to morbidity. The purpose of this study was to evaluate the efficacy of posterior instrumentation without debridement in treating spinal infections. METHODS: A retrospective medical record review was performed to identify patients treated with posterior instrumentation for spontaneous spinal infections. Success of treatment was determined based on postoperative ambulatory status, surgical complications, and need for revision surgery. RESULTS: Twenty-seven patients treated with posterior-only long-segmented rigid fixation without formal debridement of infected material were included. The most common indications for surgical intervention included spinal instability (67%), neurologic compromise (67%), and failure of prolonged antibiotic treatment (63%). There were no recurrent deep infections in 21 of 22 patients who had long-term follow-up. Four patients required revision surgery, and 3 additional patients requested elective hardware removal. Postoperatively, 70% were ambulatory with no assistive devices postoperatively. CONCLUSIONS: Vertebral osteomyelitis/discitis are challenging medical problems. Single-stage long-segment fusion without formal debridement combined with antibiotics is effective in the management of spontaneous spinal infections. CLINICAL RELEVANCE: The present study suggests that acute instrumentation without anterior debridement is associated with a resolution of infection and improvements in neurologic deficits in patient with spontaneous spine infections.

Chain length impact on the retro Diels-Alder mediated release of gemcitabine from hybrid nanoparticles towards pancreatic cancer therapy.

Previously reported gold coated iron oxide nanoparticles (Au-IONP's) have demonstrated their effectiveness as drug delivery vehicles for gemcitabine conjugated to a thermally labile Diels-Alder linker containing a chain of 4 carbon atoms (TTLD4) for the treatment of pancreatic cancer. Heat generated via laser irradiation of Au-IONPs facilitated retro Diels-Alder mediated release in a burst release profile where approximately half of all total release over 180 min occurred within the first 5 min. Two analogues of TTLD4, which differ only in linker chain length (TTLD3 & TTLD6) were synthesised and conjugated to Au-IONP's. Heat-mediated release of gemcitabine at 45 °C over 180 min from these formulations was confirmed to be based on linker length, which was 94%, 76% and 45% for TTLD3, TTLD4 and TTLD6, respectively. Drug loading of the Diels-Alder linkers in a 5:1 Drug/Au-IONP w/w ratio appears to favour those containing an even number of carbons TTLD4 (76%) & TTLD6 (57%) over TTLD3 (25%), possibly due to the linker likely being positioned perpendicular to the Au-IONP surface because of the 120 °C-C bond.

Elastomeric Porous Poly(glycerol sebacate) Methacrylate (PGSm) Microspheres as 3D Scaffolds for Chondrocyte Culture and Cartilage Tissue Engineering.

Cartilage defects can be difficult to treat; therefore, tissue engineering of cartilage is emerging as a promising potential therapy. One interesting area of research explores the delivery of cells to the cartilage defect via scaffold-based cell delivery vehicles and microsurgery. This study explores the use of novel poly(glycerol sebacate) methacrylate (PGSm)-polymerised high internal phase emulsion (polyHIPE) microspheres as scaffolds with embedded cells for cartilage tissue engineering. Porous microsphere scaffolds (100 µm-1 mm diameter) were produced from emulsions consisting of water and a methacrylate-based photocurable resin of poly(glycerol sebacate). These resins were used in conjunction with a T-junction fluidic device and an ultraviolet (UV) curing lamp to produce porous microspheres with a tuneable size. This technique produced biodegradable PGSm microspheres with similar mechanical properties to cartilage. We further explore these microspheres as scaffolds for three-dimensional culture of chondrocytes. The microspheres proved to be very efficient scaffolds for primary chondrocyte culture and were covered by a dense extracellular matrix (ECM) network during the culture period, creating a tissue disk. The presence of glycosaminoglycans (GAGs) and collagen-II was confirmed, highlighting the utility of the PGSm microspheres as a delivery vehicle for chondrocytes. A number of imaging techniques were utilised to analyse the tissue disk and develop methodologies to characterise the resultant tissue. This study highlights the utility of porous PGSm microspheres for cartilage tissue engineering.

Return to the Operating Room for Unplanned Pin Removal After Percutaneous Pinning of Supracondylar Humerus Fractures: A Retrospective Review.

BACKGROUND: Pin migration is a common complication associated with closed reduced and percutaneous pinning (CRPP) of supracondylar humerus fractures (SCHF) in children. Though this complication occurs frequently, little work has been done to elicit circumstances surrounding this complication. The purpose of this study was to evaluate patients with SCHF treated with percutaneous pins who needed to return to the operating room for pin removal. METHODS: This was a multicenter study involving children treated at 6 pediatric tertiary care centers between 2010 and 2020. Retrospective chart review was performed to identify children aged 3 to 10 years of age with a diagnosis of a SCHF. Current Procedural Terminology (CPT) codes were used to identify patients who underwent CRPP of their injuries. CPT codes for deep hardware removal requiring procedural sedation or anesthesia were used to identify patients who needed to return to the operating room for hardware removal. RESULTS: Between 2010 and 2020, 15 out of 7862 patients who were treated for SCHF at our 6 participating study centers experienced pin migration requiring a return to the operating room for pin removal, yielding a complication rate of 0.19%. Twelve (80%) of these injuries were Wilkins modification of the Gartland classification Type III, while the remaining injuries were Type II. 2-pin fixation constructs were used in nine (60%) children; 3-pin fixation constructs were used in 6 (40%) children. Pin migration was noted 23.2±7.0 days postoperatively at clinic follow-up. Four patients were noted to have multiple pins buried at follow-up. Four patients required 1-centimeter incisions for exposure of the buried pins, while surgeons were able to remove the buried pin with just a needle driver and blunt dissection in the remainder of patients. CONCLUSIONS: Pin migration is a common complication of closed reduction and percutaneous pinning of SCHF. There is variation in pin site management to prevent migration in the absence of underlying risk factors. LEVEL OF EVIDENCE: Level III.

Decision Making and Cost in Healthcare: The Patient Perspective.

Unsustainable spending and unsatisfactory outcomes have prompted a reanalysis of healthcare policy towards value. Several strategies have been proposed as part of this effort including cost sharing plans to shift costs to patients and gain-sharing models to shift risk to health systems. The patient perspective is rarely elicited in policy formation despite efforts to increase patient-centered care. We conducted a prospective study of 118 patients presenting to hand clinic to assess patient perspective of who should constrain treatment options (patient, physician, insurance company, hospital) and be responsible for costs in scenarios of clinical equipoise. We found that patients believed that insurance companies and hospitals should not constrain which treatment options are available to a patient and that physicians and patients should together influence the availability of treatment options. Patients were willing to cost share with insurance companies when choosing more expensive treatments or in the setting of non-life-threatening diseases. In addressing rising healthcare costs, patient perspectives can inform policies designed to increase value. Asking patients to cost share when choosing a more expensive treatment option in the setting of clinical equipoise could be a strategy for health systems to increase value. Level of Evidence: III (Journal of Surgical Orthopaedic Advances 32(1):023-027, 2023).

Nonsteroidal Anti-inflammatory Drugs in the Acute Post-operative Period Are Associated With an Increased Incidence of Pseudarthrosis, Hardware Failure, and Revision Surgery Following Single-level Spinal Fusion.

STUDY DESIGN: Retrospective study. SUMMARY OF BACKGROUND DATA: Research has shown that the use of NSAIDs and COX-2 inhibitors increases the risk of pseudoarthrosis following spinal fusion surgery. Pseudoarthrosis can lead to complications such as chronic pain and the need for additional surgeries. OBJECTIVE: The purpose of this study was to examine the relationship between NSAID and COX-2 inhibitor use and pseudarthrosis, hardware complications, and revision surgeries in patients undergoing posterior spinal instrumentation and fusion. METHODS: We queried the PearlDiver database using CPT and ICD-10 codes to identify patients between the ages of 50 and 85 who underwent posterior spinal instrumentation between 2016 and 2019 and experienced pseudarthrosis, hardware failure, or revision surgery. Information regarding age, Charlson Comorbidity Index, tobacco use, osteoporosis, and obesity were extracted from the database along with COX-2 or NSAID use during the first 6-week post-surgery period. Logistic regression was used to identify associations while adjusting for confounders. RESULTS: There were 178,758 patients included in the cohort; 9,586 experienced pseudarthrosis (5.36%), 2828 (1.58%) experienced hardware failure, and 10,457 (5.85%) patients underwent revision fusion surgery. Of these patients 23,602 (13.2%) filled NSAID and 5278 (2.95%) filled COX-2 prescriptions. A significantly higher proportion of patients using NSAIDs experienced pseudarthrosis, hardware failure, and revision surgery compared to patients not taking NSAIDs. COX-2 inhibitors were also associated with a significantly higher rate of pseudarthrosis, hardware failure, and revision surgery. Postoperative ketorolac use was not associated with these complications. Regression models demonstrated that both NSAIDs and COX-2 inhibitors were associated with statistically higher pseudarthrosis, hardware failure, and revision surgery rates. CONCLUSIONS: Both NSAID and COX-2 inhibitor use in the early post-surgical period may be associated with increased rates of pseudarthrosis, hardware failure, and revision surgery in patients undergoing posterior spinal instrumentation and fusion.

Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland.

BACKGROUND: Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits. METHODS: We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland. Standardized phenotypic data were collected, and exome sequencing and microarray analyses were performed to investigate novel genetic causes. We developed an iterative variant analysis pipeline and reported candidate variants to clinical teams for validation and diagnostic interpretation to inform communication with families. Multiple regression analyses were performed to evaluate factors affecting the probability of diagnosis. RESULTS: A total of 13,449 probands were included in the analyses. On average, we reported 1.0 candidate variant per parent-offspring trio and 2.5 variants per singleton proband. Using clinical and computational approaches to variant classification, we made a diagnosis in approximately 41% of probands (5502 of 13,449). Of 3599 probands in trios who received a diagnosis by clinical assertion, approximately 76% had a pathogenic de novo variant. Another 22% of probands (2997 of 13,449) had variants of uncertain significance in genes that were strongly linked to monogenic developmental disorders. Recruitment in a parent-offspring trio had the largest effect on the probability of diagnosis (odds ratio, 4.70; 95% confidence interval [CI], 4.16 to 5.31). Probands were less likely to receive a diagnosis if they were born extremely prematurely (i.e., 22 to 27 weeks' gestation; odds ratio, 0.39; 95% CI, 0.22 to 0.68), had in utero exposure to antiepileptic medications (odds ratio, 0.44; 95% CI, 0.29 to 0.67), had mothers with diabetes (odds ratio, 0.52; 95% CI, 0.41 to 0.67), or were of African ancestry (odds ratio, 0.51; 95% CI, 0.31 to 0.78). CONCLUSIONS: Among probands with severe, probably monogenic, difficult-to-diagnose developmental disorders, multimodal analysis of genomewide data had good diagnostic power, even after previous attempts at diagnosis. (Funded by the Health Innovation Challenge Fund and Wellcome Sanger Institute.).

Surgeon-Estimated Blood Loss Is Discordant With Calculated Blood Loss in Acetabular and Pelvic Fracture Surgery.

OBJECTIVES: To compare blood loss as estimated by surgeon-estimated blood loss (EBL), the Gross formula, and the HB equation in open pelvic and acetabular surgery. DESIGN: Retrospective cohort study. SETTING: Single Level I academic trauma center. PATIENTS: We included 710 patients 18-89 years of age who underwent acetabular or pelvic surgery between 2008 and 2018 for the management of fracture. INTERVENTION: Surgical treatment for the management of acetabular or pelvic fracture and blood transfusion when deemed clinically appropriate in the perioperative setting. MAIN OUTCOME MEASURES: Surgeon EBL and calculated blood loss (using the Gross formula, a Gross formula derivative, and the HB equation with both Moore and Nadler blood volume estimations). RESULTS: One hundred ninety-two patients (27%) received intraoperative blood transfusions. Surgeon EBL significantly differed from all formulas except the Gross/Nadler and the modified Gross/Nadler calculations. Gross and HB calculation methods yielded similar results in the overall cohort but yielded significantly different results in the subgroup analysis. Use of a corrective transfusion factor mildly improved correlation of the Gross equation with EBL. At high levels of blood loss, surgeon EBL predictions became more discordant with calculated blood loss values. When assessing only patients who did not receive transfusions, concordance improved. CONCLUSION: Blood loss in pelvic and acetabular surgery is challenging to quantify, and this study demonstrates discordance between formula predictions and surgeon-estimated blood loss. At higher levels of blood loss, this discrepancy worsens. This exploratory study highlights the need for the development of improved methods of quantifying blood loss in orthopaedic trauma surgery. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Quality-Improvement Initiative for Expedited Partner Therapy Provision in an Obstetrics and Gynecology Office.

OBJECTIVE: To perform a quality-improvement project to increase the rate at which expedited partner therapy is offered and prescribed at our clinic, in line with Connecticut Department of Public Health regulations. METHODS: We conducted quality-improvement interventions at an urban hospital-based outpatient clinic in Hartford, Connecticut, to improve prescribing of expedited partner therapy to at least 70% of eligible patients. We defined appropriate provision of expedited partner therapy by infection type (gonorrhea or chlamydia only per Centers for Disease Control and Prevention guidelines) and method of prescription per Connecticut Department of Public Health regulations (paper prescription or in-clinic dispensing). RESULTS: Rates of appropriate provision of expedited partner therapy improved with our interventions (21.6% vs 75.5%). We found an unexpected decrease in acceptance by patients after initiation of our interventions (81.3% vs 50.5%). CONCLUSION: We achieved our goal of improvement of rates of appropriate provision of expedited partner therapy to greater than 70% and have maintained this improvement over time. Future work should investigate potential barriers to expedited partner therapy acceptance, including type of infection, the effect of Department of Public Health regulation of prescribing options, and standard workflow in patient counseling.

Patient-Reported Outcome Measurement Information System (PROMIS) Scores in Pediatric Idiopathic Toe Walkers.

BACKGROUND: Idiopathic toe walking (ITW) can result in early contact with the health care system and be distressing for patients and their families. The natural history of ITW is poorly characterized. Deciding how and when to intervene can be difficult.Patient-reported outcomes are utilized in the clinical setting to assess patient factors and indications that may better inform treatment plans. Patient-Reported Outcomes Measurement Information System (PROMIS) is an instrument designed to collect patient-reported outcomes. Minimum clinically important differences in PROMIS metrics have been established to facilitate clinical relevance and utility of these metrics. The purpose of this study was to characterize the patient perspective of ITW by utilizing the PROMIS scores. METHODS: Retrospective chart review was performed to identify children aged 5 to 17 with a diagnosis of ITW treated at a single tertiary care center between 2017 and 2020. Inclusion criteria were a diagnosis of ITW and completion of a PROMIS questionnaire. Exclusion criteria were neurologic disease, autism, and previous surgical treatment. Demographic, physical exam, treatment, and available motion analysis data were collected. PROMIS scores for the following domains were available: Mobility, Peer Relationships, and Pain Interference. RESULTS: Forty-five children were enrolled. Seventy-three percent of PROMIS scores were patient reported while the remainder were parent reported. PROMIS score means for the cohort by domain were Mobility: 45.2±8.2 ( P <0.000); Peer Relationships: 46.4±11.6 ( P =0.047); and Pain Interference: 47.4±9.5 ( P =0.67). Motion analysis data, available for 11 children, noted age-matched gait velocity negatively correlated ( rs =-0.652, P =0.03) with Peer Relationships. No correlations were found between other aspects of gait, body mass index, or limitations in dorsiflexion and PROMIS domains. Parents reported lower Mobility scores than children did. There were no other significant differences between patient-reported and parent-reported PROMIS scores. PROMIS scores did not differ significantly between those <10 years and those ≥10 years. CONCLUSION: In this cohort of 45 otherwise healthy children without other neurologic diagnoses, there are both clinically and statistically significant differences in PROMIS means between our cohort and the healthy age-matched population. These differences manifested in worse peer relationships and mobility scores. LEVEL OF EVIDENCE: Level IV.

Trends in Management of Pediatric Distal Radius Buckle Fractures.

BACKGROUND: Distal radius buckle fractures (DRBFx) represent nearly half of the pediatric wrist injuries. DRBFx are stable injury patterns that can typically be successfully managed with brief immobilization. The purpose of this study was to evaluate opinions and preferences of pediatric orthopaedic specialists regarding the management of DRBFx. METHODS: The POSNA Trauma Quality, Safety, and Value Initiative (QSVI) Committee developed a 20-question survey regarding the treatment of DRBFx in children. The survey was sent twice to all active and candidate POSNA members in June 2020 (n=1487). Questions focused on various aspects of treatment, including type and length of immobilization, follow-up, and radiographs and on potential concerns regarding patient/family satisfaction and pain control, medicolegal concerns, misdiagnosis, and mismanagement. RESULTS: A total of 317 participants completed the survey (response rate=21.3%). In all, 69% of all respondents prefer to use a removable wrist splint, with 76% of those in practice <20 years preferring removable wrist splints compared with 51% of those in practice >20 years (χ 2 =21.7; P <0.01). Overall, 85% of participants utilize shared decision-making in discussing management options with patients and their families. The majority of participants felt that the risk of complications associated with DRBFx was very low, but concern for misdiagnosis and mismanagement have required some respondents to perform closed or open reductions. CONCLUSIONS: In 2020, the majority of respondents treat DRBFx with removable splints (69%) for 3 or fewer weeks (55%), minimal follow-up (85%), and no reimaging (64%). This marks a dramatic shift from the 2012 POSNA survey when only 29% of respondents used removable splinting for DRBFx. LEVEL OF EVIDENCE: Level II.

Salmonella Osteomyelitis in a Pediatric Patient with a Proximal Humerus Fracture: A Case Report.

CASE: A 5-year-old previously healthy girl sustained a left proximal humerus fracture after a fall from a trampoline. The injury was initially treated nonoperatively, but during routine follow-up, the patient was found to have a previously unrecognized bony erosion at the fracture site. Workup was negative for neoplasm but instead demonstrated Salmonella osteomyelitis. The patient underwent debridement and treatment with antibiotics. CONCLUSION: This is an unusual presentation of a humerus fracture in a child with concomitant Salmonella osteomyelitis. Osteomyelitis is an important diagnostic consideration when considering bony erosions in the pediatric patient, even in those patients without apparent risk factors.

Outcome Metrics in the Treatment of Carpal Tunnel Syndrome: A Systematic Review.

BACKGROUND: The purpose of this systematic review was to determine the metrics used to assess outcomes after treatment for carpal tunnel syndrome. METHODS: We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines of level I and II randomized controlled trials of treatment for carpal tunnel syndrome. We searched the PubMed/MEDLINE electronic database for studies on treatment of carpal tunnel syndrome from January 2008 to January 2018. A total of 105 studies were included in the final analysis. The metrics used to assess outcomes in each studies were collected, compared, and described. RESULTS: Nearly all the studies used a patient-reported outcome measure (PROM) to assess outcomes (94%). The most common PROMs used were the Boston Carpal Tunnel Questionnaire (60%) and the Visual Analog Scale for pain (51%). Electrophysiological testing and physical examination were also commonly used to assess outcomes (50% and 46%, respectively). Cost, sleep, and return to activities of daily living were assessed in a minority of studies (1%, 1%, and 5%, respectively). CONCLUSIONS: Successful treatment of carpal tunnel syndrome is commonly defined based on a PROM, highlighting recent efforts to measure outcomes from the patient's perspective. Other patient-centered metrics such as return to work and sleep quality, however, were rarely reported, whereas objective measures such as nerve conduction studies were prevalent. Further work is needed to determine patients' preferred method of measuring outcomes after treatment for carpal tunnel syndrome to inform goal-directed decision-making and treatment.

The 12-lead electrocardiogram of the elite female footballer as defined by different interpretation criteria across the competitive season.

ABSTRACTPre-participation screening (PPS), using a 12-lead electrocardiogram (ECG), is recommended to identify athletes at risk of sudden cardiac death (SCD). ECG interpretation criteria have been developed to address the concern arising from high false-positives in athletes. There are limited ECG data in elite female footballers. The aims of this study were to (1) compare the ECG outcomes using three published ECG criteria (European Society of Cardiology [ESC], Seattle, International) in elite female footballers and (2) compare ECG data at three different stages of a competitive season. Eighty-one elite female footballers (21 ± 4 yr) completed a medical assessment, anthropometrics, resting blood pressure and a resting 12-lead ECG. Each 12-lead ECG was interpreted in accordance with (1) ESC; (2) Seattle; (3) International Criteria to determine training-related and non-training-related ECG changes. A subset of thirteen (26 ± 4 yr) footballers had repeated resting ECG tests at three time points across the competitive season. Eighty percent of females had training-related ECG patterns. Sinus bradycardia (65%) and early repolarization (42%) were the most common. Using the ESC Criteria 25% (20/81) of the athletes were considered to have an abnormal ECG, compared to 0% using the Seattle and International Criteria, mainly due to alterations in QT length criteria. There were no clinically significant differences in ECG data across a competitive season. The Seattle and International ECG Criteria significantly reduced the number of ECG false-positives in elite female footballers and the time point of PPS within a competitive season is unlikely to alter the PPS outcomes.Abbreviations: AMSSM: American Medical Society for Sports Medicine; ANOVA: Analysis of Variance; BSA: Body Surface Area; ECG: Electrocardiogram; ESC: European Society of Cardiology; FA: Football Association; FIFA: The Fédération Internationale de Football Association (FIFA); F-MARC: FIFA Medical Assessment and Research Centre; LAE: Left atrial enlargement; LVH: Left ventricular hypertrophy; PPS: Pre-participation screening; SCD: Sudden cardiac death.