Revisiting Differences in Fourth-Year Orthopaedic Away Rotation Opportunities and Fees Among Allopathic and Osteopathic Medical Students.

Introduction: Fourth-year away rotations are an important modifiable variable proven to increase students' opportunities to match into orthopaedic surgery. The purpose of this study was to determine differences in away rotation eligibility requirements and cost of rotation between allopathic and osteopathic students during the 2023 application cycle. Eligibility requirements and fees were then compared with the 2021 application cycle. Methods: A cross-sectional study was performed during the 2023 application cycle of all nonmilitary, Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery residency programs (n = 194). Each program's website, affiliated school of medicine's website, visiting student application service portal, and Residency Explorer tool were searched for eligibility criteria, associated rotation fees, and other rotation requirements. Two-sample Z tests for proportions were utilized to compare differences in programs with differing requirements for students based on academic degree type. Data were compared statistically with previously reported data from the 2021 application cycle. Results: In 2023, there were more programs that restricted osteopathic medical students from away rotations than programs that restricted allopathic medical students (12/194, 6.2% vs. 0/194, 0.0%; p < 0.001). All 12 programs were formerly ACGME-accredited before the integration into a single accreditation system. There was a decrease in the number of programs restricting osteopathic medical students from away rotations compared with the 2021 application cycle (18/194, 9.3% vs. 12/194, 6.2%; p = 0.254). Fees associated with away rotations ranged from $25 to $4,000 for both allopathic and osteopathic students. The number of programs that charged osteopathic medical students higher rotation fees than programs that charged allopathic students when compared with the 2021 application cycles decreased (1/194, 0.5% vs. 5/194, 2.6%; p = 0.049). Conclusions: While some programs continue to have away rotation eligibility requirements that prohibit osteopathic medical students from rotating, only one residency program currently charges osteopathic medical students a higher fee to rotate than allopathic medical students.

Invasion and amplification of endogenous retroviruses in Dasyuridae marsupial genomes.

Retroviruses are an ancient viral family that have globally coevolved with vertebrates and impacted their evolution. In Australia, a continent that has been geographically isolated for millions of years, little is known about retroviruses in wildlife, despite the devastating impacts of a retrovirus on endangered koala populations. We therefore sought to identify and characterise Australian retroviruses through reconstruction of endogenous retroviruses (ERVs) from marsupial genomes, in particular the Tasmanian devil due to its high cancer incidence. We screened 19 marsupial genomes and identified over 80,000 ERV fragments which we classified into eight retrovirus clades. The retroviruses were similar to either Betaretrovirus (5/8) or Gammaretrovirus (3/8) retroviruses, but formed distinct phylogenetic clades compared to extant retroviruses. One of the clades (MEBrv 3) lost an envelope but retained retrotranspositional activity, subsequently amplifying throughout all Dasyuridae genomes. Overall, we provide insights into Australian retrovirus evolution and identify a highly active ERV within Dasyuridae genomes.

The classification of hiatal shapes and their use as a marker for complexity, operative interventions, and recurrence.

BACKGROUND: Diaphragmatic reconstruction is a vital, but challenging component of hiatal hernia and antireflux surgery. Results are optimized by minimizing axial tension along the esophagus, assessed with intra-abdominal length, and radial tension across the hiatus, which has not been standardized. We categorized hiatal openings into 4 shapes, as a surrogate for radial tension, to correlate their association with operative interventions and recurrence. METHODS: We retrospectively reviewed all primary hiatal hernias (≥3 cm) repaired at a single center between 2010 and 2020. Patients with intraoperative hiatal photos with at least 1 year of follow-up were included. The hiatal openings were classified into 4 shapes: slit, inverted teardrop, "D," and oval, and ordered in this manner of hypothesized increased complexity and tension. RESULTS: A total of 239 patients were studied, with 113 (47%) having a recurrence. Age (P < .001), proportion of paraesophageal hernias (P < .001), hernia axial length (P < .001), and hiatal width (P < .001) all increased as shape progressed from slit to inverted teardrop to "D" to oval. Mesh (P = .003) and relaxing incisions (P < .001) were more commonly employed in more advanced shapes, "D" and ovals. However, recurrence (P = .88) did not correlate with hiatal shape. CONCLUSION: Four different hiatal shapes are commonly seen during hernia repair. These shapes represent a spectrum of hernia chronicity and complexity necessitating increased use of operative measures but not correlating with recurrence. Despite failing to be a direct marker for recurrence risk, hiatal shape may serve as an intraoperative tool to inform surgeons of the potential need for additional hiatal interventions.

Recent Trends in Concomitant Distal Clavicle Excision During Rotator Cuff Repair.

The purpose of this study is to evaluate trends in distal clavicle excision (DCE) in association with arthroscopic rotator cuff repair (RCR) from 2010 to 2019. The National Surgical Quality Improvement Program database was queried to identify all patients who underwent arthroscopic RCR from January 1, 2010 to December 31, 2019, and was further subdivided into procedure type: (1) isolated RCR; and (2) RCR with arthroscopic or open DCE. The proportion of each surgery type, by year and within groups, was calculated. The Cochran-Armitage test for trend was used to analyze yearly proportions of RCR with concomitant DCE. In a sample size of 19,163 patients, the proportion of RCR with DCE decreased from 51.2% to 40.8% (r = -0.830; p = 0.003). Although the results of this study suggest that surgeons are performing fewer DCEs in the setting of RCR, many DCEs are still being done. (Journal of Surgical Orthopaedic Advances 33(2):077-079, 2024).

Pain Relief Interventions in Australian Livestock Husbandry: A Review of Animal Welfare and Pain Duration.

In veterinary medicine and livestock production, ensuring good animal husbandry is vital for the physical and emotional wellbeing of animals under our care. Pain poses challenges for assessment and mitigation, especially in species unable to express pain overtly. This review examines current pain mitigation interventions in routine husbandry, focuses on the duration of pain after procedures and implications for animal welfare. Pain behaviours have been observed for days or weeks after regular husbandry procedures, and many studies have noted pain-related behaviour persisting until study finalisation, suggesting potential undocumented pain beyond study completion. Current products registered in Australia for pain mitigation in livestock primarily target immediate pain associated with procedures. The future of pain relief in livestock demands longer-acting solutions to address post-procedural pain adequately. Providing pain relief for at least 72 h post surgery is recommended, but current products require retreatment intervals to achieve this, posing practical challenges, especially in livestock. Methods of pain relief provision, such as voluntary consumption of medicated feed, transdermal medication delivery and long-acting formulations offer potential solutions for prolonged pain relief, with research ongoing in these areas. There is a need for further research and development of longer-acting pain relief to ensure optimal welfare of livestock.

WHO global research priorities for sexually transmitted infections.

Sexually transmitted infections (STIs) are widespread worldwide and negatively affect sexual and reproductive health. Gaps in evidence and in available tools have long hindered STI programmes and policies, particularly in resource-limited settings. In 2022, WHO initiated a research prioritisation process to identify the most important STI research areas to address the global public health need. Using an adapted Child Health and Nutrition Research Initiative methodology including two global stakeholder surveys, the process identified 40 priority STI research needs. The top priorities centred on developing and implementing affordable, feasible, rapid point-of-care STI diagnostic tests and new treatments, especially for gonorrhoea, chlamydia, and syphilis; designing new multipurpose prevention technologies and vaccines for STIs; and collecting improved STI epidemiologic data on both infection and disease outcomes. The priorities also included innovative programmatic approaches, such as new STI communication and partner management strategies. An additional six research areas related to mpox (formerly known as monkeypox) reflect the need for STI-related research during disease outbreaks where sexual transmission can have a key role. These STI research priorities provide a call to action for focus, investment, and innovation to address existing roadblocks in STI prevention, control, and management to advance sexual and reproductive health and wellbeing for all.

Impact of the COVID-19 Pandemic on Hospital Admission Rate, Length of Stay, and Mortality Rate for Patients with Chronic Obstructive Pulmonary Disease Exacerbation: A Retrospective Study.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of hospital admissions. Coronavirus disease 2019 (COVID-19) has large impact on patients with pulmonary diseases. The purpose of the study is to evaluate the impact of COVID-19 on patients with AECOPD. Method: Retrospective study with two cohorts, the first period included patients with AECOPD before COVID-19 pandemic; the second period included patients with AECOPD since the beginning of COVID-19 pandemic. The length of stay (LOS), number of patients requiring mechanical ventilation, and allcause mortality were calculated. Results: There was a total of 55 (44.72%) patients in the pre-COVID period compared to 68 (55.28%) patients in the COVID period. In the pre-COVID period: 14 (19.44%) had hypertension, 26(36.11%) had diabetes, 27(37.50%) had ischemic heart disease, 3(4.17%) had myocardial infarction; in the COVID period: 20 (29.41%) had hypertension, 24(35.29%) had diabetes, 27(39.71%) had ischemic heart disease, 1(1.47) had myocardial infarction. The LOS was shorter in pre-COVID period compared to COVID period, 6.51(SD 5.02) days vs 8.91(SD7.88) days with P-value of 0.042 respectively. The total number of patients needing mechanical ventilation in pre-COVID period was similar to the COVID period with P-value of 0.555. All-cause mortality number was 2 (3.64%) in the pre-COVID period compared to 6 (8.82%) in COVID period with P-value of 0.217. Conclusion: Study results revealed significant difference in length of stay for patients with AECOPD, patient in COVID period had increased LOS compared to pre-COVID period. There was no significant difference in the other parameters.

Morbidity and mortality after antireflux and hiatal hernia surgery across a spectrum of ages.

BACKGROUND: Antireflux surgery (ARS) and hiatal hernia repair (HHR) are common surgical procedures with modest morbidity. Increasing age is a risk factor for complications; however, details regarding acute morbidity are lacking. This study aimed to describe the incidence rates and types of morbidities across the spectrum of ages. METHODS: A total of 2342 consecutive cases were retrospectively reviewed from 2003 to 2020 for 30-day complications. All complications were assessed using the Clavien-Dindo (CD) grading system. Patients were divided into 5 age groups: ≤59, 60 to 69, 70 to 79, 80 to 89, and ≥90 years. RESULTS: The numbers per age group were 1100 patients aged ≤59 years, 684 patients aged 60 to 69 years, 458 patients aged 70 to 79 years, 458 patients aged 80 to 89 years, and 6 patients aged ≥90 years. A total of 427 complications (18.2%) occurred, including 2 mortalities, each in the 60- to 69-year age group and the 70- to 79-year age group, for a mortality rate of 0.2%. The complication rate increased from 13.5% (149) in patients aged ≤59 years to 35.0% (35) in patients aged ≥80 years (P = .006), with CD grades I and II accounting for >70% of complications, except in patients aged ≥80 years (57.1%). CD grades IIIa and IIIb were higher in patients aged ≥80 years (26.5% [P = .001] and 11.8% [P = .021], respectively). CD grade IVa and IVb complications were rare overall. CONCLUSION: There is a modest rate of morbidity that increases as patients age, regardless of hernia type, elective or primary surgery, with most being minor complications (CD grade≤II). Our data should help patients, referring physicians, and surgeons counsel patients regarding the effect of increasing age in ARS and HHR.

Impact of interventions to reduce nosocomial transmission of SARS-CoV-2 in English NHS Trusts: a computational modelling study.

BACKGROUND: Prior to September 2021, 55,000-90,000 hospital inpatients in England were identified as having a potentially nosocomial SARS-CoV-2 infection. This includes cases that were likely missed due to pauci- or asymptomatic infection. Further, high numbers of healthcare workers (HCWs) are thought to have been infected, and there is evidence that some of these cases may also have been nosocomially linked, with both HCW to HCW and patient to HCW transmission being reported. From the start of the SARS-CoV-2 pandemic interventions in hospitals such as testing patients on admission and universal mask wearing were introduced to stop spread within and between patient and HCW populations, the effectiveness of which are largely unknown. MATERIALS/METHODS: Using an individual-based model of within-hospital transmission, we estimated the contribution of individual interventions (together and in combination) to the effectiveness of the overall package of interventions implemented in English hospitals during the COVID-19 pandemic. A panel of experts in infection prevention and control informed intervention choice and helped ensure the model reflected implementation in practice. Model parameters and associated uncertainty were derived using national and local data, literature review and formal elicitation of expert opinion. We simulated scenarios to explore how many nosocomial infections might have been seen in patients and HCWs if interventions had not been implemented. We simulated the time period from March-2020 to July-2022 encompassing different strains and multiple doses of vaccination. RESULTS: Modelling results suggest that in a scenario without inpatient testing, infection prevention and control measures, and reductions in occupancy and visitors, the number of patients developing a nosocomial SARS-CoV-2 infection could have been twice as high over the course of the pandemic, and over 600,000 HCWs could have been infected in the first wave alone. Isolation of symptomatic HCWs and universal masking by HCWs were the most effective interventions for preventing infections in both patient and HCW populations. Model findings suggest that collectively the interventions introduced over the SARS-CoV-2 pandemic in England averted 400,000 (240,000 - 500,000) infections in inpatients and 410,000 (370,000 - 450,000) HCW infections. CONCLUSIONS: Interventions to reduce the spread of nosocomial infections have varying impact, but the package of interventions implemented in England significantly reduced nosocomial transmission to both patients and HCWs over the SARS-CoV-2 pandemic.

Thirty- and 90-Day Morbidity and Mortality by Clavien-Dindo 30 and 90 Days after Surgery for Antireflux and Hiatal Hernia.

BACKGROUND: The historic morbidity and mortality rates of anti-reflux and hiatal hernia surgery are reported as 3-21% and 0.2-0.5%, respectively. These data come from either large national/population level or small institutional studies, with the former focusing on broad 30-day outcomes while lacking granular data on complications and their severity. Institutional studies tend to focus on long-term and quality of life outcomes. Our objective is to describe and evaluate the incidence of 30 and 90-day morbidity and mortality in a large, single institution dataset. STUDY DESIGN: We retrospectively reviewed 2342 cases of anti-reflux and hiatal hernia surgery from 2003-2020 for intra-operative complications causing post-operative sequelae, as well as morbidity and mortality within 90 days. All complications were graded using the Clavien-Dindo (CD) Grading System. The highest-grade of complication was used per patient during 30-day and 31-90-day intervals. RESULTS: Out of 2342 patients, the overall 30-day morbidity and mortality rates were 18.2% (427/2342) and 0.2% (4/2342), respectively. Most of the complications were CD<3a at 13.1% (306/2342). In the 31-90-day post-operative period, morbidity and mortality rates decreased to 3.1% (78/2338) and 0.09% (2/2338). CD<3a complications accounted for 1.9% (42/2338). CONCLUSIONS: Anti-reflux and hiatal hernia surgery are safe operations with rare mortality and modest rates of morbidity. However, the majority of complications patients experience are minor (CD<3a) and are easily managed. A minority of patients will experience major complications (CD≥3a) that require additional procedures and management to secure a safe outcome. These data are helpful to inform patients of the risks of surgery, and guide physicians for optimal consent.

Inflammatory Myofibroblastic Tumor After Receiving Treatment for Non-small Cell Carcinoma.

Inflammatory pseudotumor encompasses a spectrum of both neoplastic and non-neoplastic conditions characterized by a histological pattern featuring a proliferation of cytologically bland spindle cells, accompanied by a prominent chronic inflammatory infiltrate. Within this spectrum, inflammatory myofibroblastic tumor (IMT) has emerged as a distinct entity over the past two decades, marked by unique clinical, pathological, and molecular characteristics. Typically affecting the visceral soft tissues of children and adolescents, IMT exhibits a propensity for local recurrence while posing a minimal risk of distant metastasis. They are extremely rare in adults, constituting less than 1% of adult lung tumors. Our patient, a 63-year-old female, has an intricate medical background, encompassing chronic obstructive pulmonary disease (COPD), a previous history of smoking (35 pack-years, quit a year before admission), coronary artery disease, non-obstructive hypertrophic cardiomyopathy, and obstructive sleep apnea. Presenting with a diagnostic dilemma, she recently received treatment for non-small cell carcinoma with radiation therapy, which has evolved into a swiftly advancing case of IMT.

CNVoyant: A Highly Performant and Explainable Multi-Classifier Machine Learning Approach for Determining the Clinical Significance of Copy Number Variants.

The precise classification of copy number variants (CNVs) presents a significant challenge in genomic medicine, primarily due to the complex nature of CNVs and their diverse impact on genetic disorders. This complexity is compounded by the limitations of existing methods in accurately distinguishing between benign, uncertain, and pathogenic CNVs. Addressing this gap, we introduce CNVoyant, a machine learning-based multi-class framework designed to enhance the clinical significance classification of CNVs. Trained on a comprehensive dataset of 52,176 ClinVar entries across pathogenic, uncertain, and benign classifications, CNVoyant incorporates a broad spectrum of genomic features, including genome position, disease-gene annotations, dosage sensitivity, and conservation scores. Models to predict the clinical significance of copy number gains and losses were trained independently. Final models were selected after testing 29 machine learning architectures and 10,000 hyperparameter combinations each for deletions and duplications via 5-fold cross-validation. We validate the performance of the CNVoyant by leveraging a comprehensive set of 21,574 CNVs from the DECIPHER database, a highly regarded resource known for its extensive catalog of chromosomal imbalances linked to clinical outcomes. Compared to alternative approaches, CNVoyant shows marked improvements in precision-recall and ROC AUC metrics for binary pathogenic classifications while going one step further, offering multi-classification of clinical significance and corresponding SHAP explainability plots. This large-scale validation demonstrates CNVoyant's superior accuracy and underscores its potential to aid genomic researchers and clinical geneticists in interpreting the clinical implications of real CNVs.

Industry Payments to Foot and Ankle-Trained Orthopedic Surgeons: An Analysis of the Open Payments Database From 2014 to 2019.

Introduction The authors examined if the transparency in industry payments to foot and ankle-trained orthopedic surgeons resulted in the following changes to the (1) median general payments to surgeons, (2) trend in median payments to surgeons across all subcategory payments, and (3) trend in median payments to surgeons in 11 regions of the United States. Methods A retrospective review of the Centers for Medicare and Medicaid Services (CMS) and Open Payments Database (OPD) was performed to identify all industry payments made by drug and medical device companies to orthopedic surgeons (N = 3,835) between January 1, 2014, and December 31, 2019. Descriptive statistics were calculated, and trend analyses in annual payments, number of payments to surgeons per year, payment subtypes, and regional distributions were analyzed. Results A total of 53,280 payments totaling $53,454,850.56 were made to orthopedic foot and ankle surgeons between 2014 and 2019. Mean and median payments were $1,003.28 and $60.19, respectively. Statistically significant differences in mean payment amounts were observed by year (p = 0.001) with a highly statistically significant, strong increase in the number of payments made over the six-year period (r = 0.97, p < 0.001). The greatest increases in median individual payments were observed for gifts (277.1%; r = 0.18, p = 0.05), education (250.6%; r = 0.17, p < 0.001), and royalties and licensing (72.1%; r = 0.05, p = 0.04). Statistically significant increasing trends in median payments over time were observed for the Northeast (p < 0.001) and South regions (p < 0.001). Discussion The results of this study demonstrate the increase in payments made across the six-year time period. The study demonstrates that there is a shift in the type of payments from speaker fees, entertainment, and lodging to education, gifts, honoraria, royalties, and consulting. Conclusion Since the OPD release, no significant decrease was identified in the financial relationship between foot and ankle surgeons and the industry; rather, an increase was observed. This increase in education, royalties, and consulting shows that more foot and ankle surgeons are getting involved in the industry, contrary to expectations. The partnership between industry and physicians can help to improve innovation and bring new ideas to the future of orthopedics.

Study protocol for a pragmatic randomised controlled trial of comparing enhanced acceptance and commitment therapy plus (+) added to usual aftercare versus usual aftercare only, in patients living with or beyond cancer: SUrvivors' Rehabilitation Evaluation after CANcer (SURECAN) trial.

BACKGROUND: Two million people in the UK are living with or beyond cancer and a third of them report poor quality of life (QoL) due to problems such as fatigue, fear of cancer recurrence, and concerns about returning to work. We aimed to develop and evaluate an intervention based on acceptance and commitment therapy (ACT), suited to address the concerns of cancer survivors and in improving their QoL. We also recognise the importance of exercise and vocational activity on QoL and therefore will integrate options for physical activity and return to work/vocational support, thus ACT Plus (+). METHODS: We will conduct a multi-centre, pragmatic, theory driven, randomised controlled trial. We will assess whether ACT+ including usual aftercare (intervention) is more effective and cost-effective than usual aftercare alone (control). The primary outcome is QoL of participants living with or beyond cancer measured using the Functional Assessment of Cancer Therapy: General scale (FACT-G) at 52 weeks. We will recruit 344 participants identified from secondary care sites who have completed hospital-based treatment for cancer with curative intent, with low QoL (determined by the FACT-G) and randomise with an allocation ratio of 1:1 to the intervention or control. The intervention (ACT+) will be delivered by NHS Talking Therapies, specialist services, and cancer charities. The intervention consists of up to eight sessions at weekly or fortnightly intervals using different modalities of delivery to suit individual needs, i.e. face-to-face sessions, over the phone or skype. DISCUSSION: To date, there have been no robust trials reporting both clinical and cost-effectiveness of an ACT based intervention for people with low QoL after curative cancer treatment in the UK. We will provide high quality evidence of the effectiveness and cost-effectiveness of adding ACT+ to usual aftercare provided by the NHS. If shown to be effective and cost-effective then commissioners, providers and cancer charities will know how to improve QoL in cancer survivors and their families. TRIAL REGISTRATION: ISRCTN: ISRCTN67900293 . Registered on 09 December 2019. All items from the World Health Organization Trial Registration Data Set for this protocol can be found in Additional file 2 Table S1.

Cost-effectiveness of 4CMenB vaccination against gonorrhea: importance of dosing schedule, vaccine sentiment, targeting strategy, and duration of protection.

BACKGROUND: Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination. METHODS: Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection. RESULTS: Vaccination with one or two primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering "Vaccination-according-to-Risk" (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more-restrictive strategy of "Vaccination-on-Diagnosis" (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR(2-dose) saves £7.62M(95%CrI:1.15-17.52) and gains 81.41(28.67-164.23) QALYs over 10 years; VoD(2-dose) saves £3.40M(0.48-7.71) and gains 41.26(17.52-78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by ∼30%(VoD) or ∼60%(VaR). CONCLUSIONS: At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.

The perceptual timescape: Perceptual history on the sub-second scale.

There is a high-capacity store of brief time span (∼1000 ms) which information enters from perceptual processing, often called iconic memory or sensory memory. It is proposed that a main function of this store is to hold recent perceptual information in a temporally segregated representation, named the perceptual timescape. The perceptual timescape is a continually active representation of change and continuity over time that endows the perceived present with a perceived history. This is accomplished primarily by two kinds of time marking information: time distance information, which marks all items of information in the perceptual timescape according to how far in the past they occurred, and ordinal temporal information, which organises items of information in terms of their temporal order. Added to that is information about connectivity of perceptual objects over time. These kinds of information connect individual items over a brief span of time so as to represent change, persistence, and continuity over time. It is argued that there is a one-way street of information flow from perceptual processing either to the perceived present or directly into the perceptual timescape, and thence to working memory. Consistent with that, the information structure of the perceptual timescape supports postdictive reinterpretations of recent perceptual information. Temporal integration on a time scale of hundreds of milliseconds takes place in perceptual processing and does not draw on information in the perceptual timescape, which is concerned with temporal segregation, not integration.

Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-label Study.

Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping in these patients has the potential to be highly therapeutic through restoration of full-length dystrophin expression. We conducted a 48-week open label study of casimersen and golodirsen in 3 subjects with an exon 45 or 53 duplication. Two subjects (aged 18 and 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, and cardiac function appeared stable in the 2 subjects in whom they could be evaluated. Dystrophin expression increased from 0.94 % ±0.59% (mean±SD) of normal to 5.1% ±2.9% by western blot. Percent dystrophin positive fibers also rose from 14% ±17% at baseline to 50% ±42% . Our results provide initial evidence that the use of exon-skipping drugs may increase dystrophin levels in patients with single-exon duplications.

Industry Payments to Orthopedic Surgeons Among All Subspecialties: An Analysis of the Open Payments Database From 2014 to 2019.

Introduction Since the passage of the Physician Payments Sunshine Act in 2010, the Centers for Medicare and Medicaid Services (CMS) started the National Physician Payment Transparency Program and Open Payments Database (OPD), which allowed for public access to financial disclosures between physicians and industry. Although orthopedic surgeons receive the highest average payments when compared to other specialties, there has been limited data evaluating these payments among the different orthopedic subspecialties. The purpose of this study was to analyze all industry payments made across all subspecialties among orthopedic surgeons. Methods A retrospective review of the CMS OPD was performed to identify all industry payments made by drug and medical device companies to orthopedic surgeons (N = 28,475) between January 1, 2014, and December 31, 2019. Descriptive statistics were calculated for the number, individual value, and total value of industry payments, stratified by payment type and orthopedic subspecialty. Results A total of 1,048,573 payments (approximately $1.6 billion) were made to orthopedic surgeons between 2014 and 2019. The average orthopedic surgeon received 6.14 payments per year (SD = 29.39), with a mean individual payment amount of $1,542.32. Royalties or licensing comprised the greatest proportion of open payments, followed by consulting fees. Adult reconstruction (M = $225,131.10) and spine (M = $197,404.74) received significantly greater total payments when compared to all other subspecialties (all p-values ≤ 0.001). Differences in total payments made to trauma (M = $73,789.65), sports medicine (M = $60,988.09), foot and ankle (M = $45,007.45), pediatric orthopaedics (M = $35,898.54), general orthopaedics (M = $28,405.81), and hand (M = $14,027.76) were all found to be statistically equivalent (all p--values > 0.20). Discussion Increased collaboration between physicians and industry has resulted in the rapid advancement of innovation that can have sizeable financial implications among orthopedic surgeons. There exists significant heterogeneity in open payments made to orthopedic surgeons when stratified by subspecialty. Adult reconstructive and spine surgeons were the most compensated whereas hand and general orthopaedic surgeons received the least.

Use of a meningococcal group B vaccine (4CMenB) in populations at high risk of gonorrhoea in the UK.

The meningococcal group B vaccine, 4CMenB, is a broad-spectrum, recombinant protein vaccine that is licensed for protection against meningococcal group B disease in children and adults. Over the past decade, several observational studies supported by laboratory studies have reported protection by 4CMenB against gonorrhoea, a sexually transmitted infection caused by Neisseria gonorrhoeae. Gonorrhoea is a major global public health problem, with rising numbers of diagnoses and increasing resistance to multiple antibiotics. In England, more than 82 000 cases of gonorrhoea were diagnosed in 2022, with nearly half of the cases diagnosed among gay, bisexual, and other men who have sex with men. There are currently no licensed vaccines against gonorrhoea but 4CMenB is estimated to provide 33-47% protection against gonorrhoea. On Nov 10, 2023, the UK Joint Scientific Committee on Vaccination and Immunisation agreed that a targeted programme should be initiated using 4CMenB to prevent gonorrhoea among individuals at higher risk of infection attending sexual health services in the UK. This decision was made after reviewing evidence from retrospective and prospective observational studies, laboratory and clinical data, national surveillance reports, and health economic analyses. In this Review, we summarise the epidemiology of invasive meningococcal disease and gonorrhoea in England, the evidence supporting the use of 4CMenB for protection against gonorrhoea, and the data needed to inform long-term programme planning and extension to the wider population.