Reverse total shoulder replacement versus anatomical total shoulder replacement for osteoarthritis: population based cohort study using data from the National Joint Registry and Hospital Episode Statistics for England.

OBJECTIVES: To answer a national research priority by comparing the risk-benefit and costs associated with reverse total shoulder replacement (RTSR) and anatomical total shoulder replacement (TSR) in patients having elective primary shoulder replacement for osteoarthritis. DESIGN: Population based cohort study using data from the National Joint Registry and Hospital Episode Statistics for England. SETTING: Public hospitals and publicly funded procedures at private hospitals in England, 2012-20. PARTICIPANTS: Adults aged 60 years or older who underwent RTSR or TSR for osteoarthritis with intact rotator cuff tendons. Patients were identified from the National Joint Registry and linked to NHS Hospital Episode Statistics and civil registration mortality data. Propensity score matching and inverse probability of treatment weighting were used to balance the study groups. MAIN OUTCOME MEASURES: The main outcome measure was revision surgery. Secondary outcome measures included serious adverse events within 90 days, reoperations within 12 months, prolonged hospital stay (more than three nights), change in Oxford Shoulder Score (preoperative to six month postoperative), and lifetime costs to the healthcare service. RESULTS: The propensity score matched population comprised 7124 RTSR or TSR procedures (126 were revised), and the inverse probability of treatment weighted population comprised 12 968 procedures (294 were revised) with a maximum follow-up of 8.75 years. RTSR had a reduced hazard ratio of revision in the first three years (hazard ratio local minimum 0.33, 95% confidence interval 0.18 to 0.59) with no clinically important difference in revision-free restricted mean survival time, and a reduced relative risk of reoperations at 12 months (odds ratio 0.45, 95% confidence interval 0.25 to 0.83) with an absolute risk difference of -0.51% (95% confidence interval -0.89 to -0.13). Serious adverse events and prolonged hospital stay risks, change in Oxford Shoulder Score, and modelled mean lifetime costs were similar. Outcomes remained consistent after weighting. CONCLUSIONS: This study's findings provide reassurance that RTSR is an acceptable alternative to TSR for patients aged 60 years or older with osteoarthritis and intact rotator cuff tendons. Despite a significant difference in the risk profiles of revision surgery over time, no statistically significant and clinically important differences between RTSR and TSR were found in terms of long term revision surgery, serious adverse events, reoperations, prolonged hospital stay, or lifetime healthcare costs.

Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID-19 Pandemic.

OBJECTIVE: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control. RESULTS: More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. CONCLUSION: Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.

Impact of Prolonged Sport Stoppage on Knee Injuries in High School Athletes: An Ecological Study.

CONTEXT: In March 2020, public health concerns resulted in school closure throughout the United States. The prolonged sport cessation may affect knee injury risk in high school athletes. The purpose of this study was to describe and compare risk of knee injuries in high school athletes during 2019-2020 and 2020-2021 academic years, and stratify by gender, severity, mechanism of injury, injury type, and knee anatomic region. DESIGN: Historical-prospective cohort study. METHODS: This historical-prospective cohort study included 176 schools in 6 states matched by sport participation in control and COVID years from July 1, 2019 to June 30, 2021. Injury rates per 1000 athletes per year were calculated with 95% confidence intervals. A negative binomial regression was performed to assess potential differences in knee injuries between academic years. RESULTS: 94,847 and 72,521 high school athletes participated in the 2019-2020 (19-20) and 2020-2021 (20-21) seasons. Knee injury risk was higher in the 20-21 season (19-20: 28.89% [27.82-29.96]; 20-21: 33.82% [32.50-35.14]). Risk increased for male athletes from 2019-2020 to 2020-2021 (19-20: 29.42% [28.01-30.83]; 20-21: 40.32% [38.89-41.75]). Female knee injury risk was similar between years (19-20: 25.78% [24.29-27.27]; 20-21: 26.03% [24.31-27.75]). Knee injuries increased by a ratio of 1.2 ([95% CI, 1.1-1.3], P < .001) during 2020-2021. CONCLUSIONS: Knee injury risk and relative risk increased among males in 2020-2021. Results indicate changes in knee injury risk following return from COVID shelter in place among high school athletes and implicate potential negative downstream effects of interrupted sports training and participation on high school injury risk.

Association between ethnic background and COVID-19 morbidity, mortality and vaccination in England: a multistate cohort analysis using the UK Biobank.

OBJECTIVES: Despite growing evidence suggesting increased COVID-19 mortality among people from ethnic minorities, little is known about milder forms of SARS-CoV-2 infection. We sought to explore the association between ethnic background and the probability of testing, testing positive, hospitalisation, COVID-19 mortality and vaccination uptake. DESIGN: A multistate cohort analysis. Participants were followed between 8 April 2020 and 30 September 2021. SETTING: The UK Biobank, which stores medical data on around half a million people who were recruited between 2006 and 2010. PARTICIPANTS: 405 541 subjects were eligible for analysis, limited to UK Biobank participants living in England. 23 891 (6%) of participants were non-white. PRIMARY AND SECONDARY OUTCOME MEASURES: The associations between ethnic background and testing, testing positive, hospitalisation and COVID-19 mortality were studied using multistate survival analyses. The association with single and double-dose vaccination was also modelled. Multistate models adjusted for age, sex and socioeconomic deprivation were fitted to estimate adjusted HRs (aHR) for each of the multistate transitions. RESULTS: 18 172 (4.5%) individuals tested positive, 3285 (0.8%) tested negative and then positive, 1490 (6.9% of those tested positive) were hospitalised, and 129 (0.6%) tested positive at the moment of hospital admission (ie, direct hospitalisation). Finally, 662 (17.4%) died after admission. Compared with white participants, Asian participants had an increased risk of negative to positive transition (aHR 1.24 (95% CI 1.02 to 1.52)), testing positive (95% CI 1.44 (1.33 to 1.55)) and direct hospitalisation (1.61 (95% CI 1.28 to 2.03)). Black participants had an increased risk of hospitalisation following a positive test (1.71 (95% CI 1.29 to 2.27)) and direct hospitalisation (1.90 (95% CI 1.51 to 2.39)). Although not the case for Asians (aHR 1.00 (95% CI 0.98 to 1.02)), black participants had a reduced vaccination probability (0.63 (95% CI 0.62 to 0.65)). In contrast, Chinese participants had a reduced risk of testing negative (aHR 0.64 (95% CI 0.57 to 0.73)), of testing positive (0.40 (95% CI 0.28 to 0.57)) and of vaccination (0.78 (95% CI 0.74 to 0.83)). CONCLUSIONS: We identified inequities in testing, vaccination and COVID-19 outcomes according to ethnicity in England. Compared with whites, Asian participants had increased risks of infection and admission, and black participants had almost double hospitalisation risk, and a 40% lower vaccine uptake.

Genetic risk, adherence to healthy lifestyle and acute cardiovascular and thromboembolic complications following SARS-COV-2 infection.

Current understanding of determinants for COVID-19-related cardiovascular and thromboembolic (CVE) complications primarily covers clinical aspects with limited knowledge on genetics and lifestyles. Here, we analysed a prospective cohort of 106,005 participants from UK Biobank with confirmed SARS-CoV-2 infection. We show that higher polygenic risk scores, indicating individual's hereditary risk, were linearly associated with increased risks of post-COVID-19 atrial fibrillation (adjusted HR 1.52 [95% CI 1.44 to 1.60] per standard deviation increase), coronary artery disease (1.57 [1.46 to 1.69]), venous thromboembolism (1.33 [1.18 to 1.50]), and ischaemic stroke (1.27 [1.05 to 1.55]). These genetic associations are robust across genders, key clinical subgroups, and during Omicron waves. However, a prior composite healthier lifestyle was consistently associated with a reduction in all outcomes. Our findings highlight that host genetics and lifestyle independently affect the occurrence of CVE complications in the acute infection phrase, which can guide tailored management of COVID-19 patients and inform population lifestyle interventions to offset the elevated cardiovascular burden post-pandemic.

Random effects modelling versus logistic regression for the inclusion of cluster-level covariates in propensity score estimation: A Monte Carlo simulation and registry cohort analysis.

Purpose: Surgeon and hospital-related features, such as volume, can be associated with treatment choices and outcomes. Accounting for these covariates with propensity score (PS) analysis can be challenging due to the clustered nature of the data. We studied six different PS estimation strategies for clustered data using random effects modelling (REM) compared with logistic regression. Methods: Monte Carlo simulations were used to generate variable cluster-level confounding intensity [odds ratio (OR) = 1.01-2.5] and cluster size (20-1,000 patients per cluster). The following PS estimation strategies were compared: i) logistic regression omitting cluster-level confounders; ii) logistic regression including cluster-level confounders; iii) the same as ii) but including cross-level interactions; iv), v), and vi), similar to i), ii), and iii), respectively, but using REM instead of logistic regression. The same strategies were tested in a trial emulation of partial versus total knee replacement (TKR) surgery, where observational versus trial-based estimates were compared as a proxy for bias. Performance metrics included bias and mean square error (MSE). Results: In most simulated scenarios, logistic regression, including cluster-level confounders, led to the lowest bias and MSE, for example, with 50 clusters × 200 individuals and confounding intensity OR = 1.5, a relative bias of 10%, and MSE of 0.003 for (i) compared to 32% and 0.010 for (iv). The results from the trial emulation also gave similar trends. Conclusion: Logistic regression, including patient and surgeon-/hospital-level confounders, appears to be the preferred strategy for PS estimation.

Upper Quarter Injury Rates and Risk in United States High School Athletes Prior To and During the Prolonged Sport Stoppage.

Background: Upper quarter injuries are a serious problem in high school sports. The distinctive differences in males and females and within sports concerning specific upper quarter body parts necessitates the need to evaluate these injuries across these groups. The COVID-19 pandemic has created an opportunity to evaluate the potential added burden abrupt and prolonged sport stoppage had on upper quarter injury risk. Hypothesis/Purpose: To 1) describe and compare upper quarter injury rates and risk in high school athletes in the 2019-2020 and 2020-2021 academic school years; 2) examine injuries by gender, sport, injury type, and location of injury. Methods: An ecological study of the athletes from 176 high schools over six states, matching high schools between 2019-2020 (19-20) and 2020-2021 (20-21) years was performed. Injuries were reported by at least one high school athletic trainer assigned to each school into a centralized database and data collected from July 1, 2019, to June 30, 2021. Injury rates were calculated per 1,000 athletes per academic year. Interrupted time series models assessed the incidence ratio between academic years. Results: A total of 98,487 athletes from all sports participated in 19-20 and 72,521 in 20-21. Upper quarter injury rates increased in from 19-20 [41.9 (40.6, 43.1)] to 20-21 [50.7 (48.1, 51.3)]. Upper quarter injury risk [1.5 (1.1, 2.2)] was greater in 20-21 compared to 19-20. Females did not demonstrate increased injury rates between 19-20 [31.1 (29.4, 32.7)] to 20-21 [28.1 (26.4, 30.0)]. Males reported increased injury rates from 19-20 [50.3 (48.5, 52.2)] to 20-21 [67.7 (65.2, 70.2)]. Increased injury for the shoulder, elbow, and hand were reported in 20-21. Collision, field, and court upper quarter injury rates were increased in 20-21. Discussion: Upper quarter injury rates and injury risk were greater during the 2020-2021 school year than in the prior year. Males demonstrated increased upper quarter injury rates, while females did not. Return to play protocols for high school athletes should be considered following abrupt sport stoppage. Level of Evidence: 2.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The impact of COVID-19 certification mandates on the number of cases of and hospitalizations with COVID-19 in the UK: A difference-in-differences analysis.

Background: Mandatory COVID-19 certification, showing proof of vaccination, negative test, or recent infection to access to public venues, was introduced at different times in the four countries of the UK. We aim to study its effects on the incidence of cases and hospital admissions. Methods: We performed Negative binomial segmented regression and ARIMA analyses for four countries (England, Northern Ireland, Scotland and Wales), and fitted Difference-in-Differences models to compare the latter three to England, as a negative control group, since it was the last country where COVID-19 certification was introduced. The main outcome was the weekly averaged incidence of COVID-19 cases and hospital admissions. Results: COVID-19 certification led to a decrease in the incidence of cases and hospital admissions in Northern Ireland, as well as in Wales during the second half of November. The same was seen for hospital admissions in Wales and Scotland during October. In Wales the incidence rate of cases in October already had a decreasing tendency, as well as in England, hence a particular impact of COVID-19 certification was less obvious. Method assumptions for the Difference-in-Differences analysis did not hold for Scotland. Additional NBSR and ARIMA models suggest similar results, while also accounting for correlation in the latter. The assessment of the effect in England itself leads one to believe that this intervention might not be strong enough for the Omicron variant, which was prevalent at the time of introduction of COVID-19 certification in the country. Conclusions: Mandatory COVID-19 certification reduced COVID-19 transmission and hospitalizations when Delta predominated in the UK, but lost efficacy when Omicron became the most common variant.

Higher rates of concussion following COVID-19 infection in high school athletes.

OBJECTIVE: To compare concussion rates (CRs) over one academic year in high school athletes with and without a COVID-19 infection prior to concussion. METHODS: Illness and concussion were prospectively reported for male and female high school athletes across six states over one academic year in the Players Health Rehab surveillance system. Concussion was truncated to 60 days following recovery and return to sport from COVID-19. CRs were estimated per 1000 athletes per academic year and stratified by those who tested positive for COVID-19 infection (with COVID-19) and those who did not (no COVID-19). Poisson regression analyses estimated rate ratio (RR) of concussion controlling for state, gender and an offset of the log athlete participation (with COVID-19 and no COVID-19). RESULTS: Of 72 522 athletes, 430 COVID-19 infections and 1273 concussions were reported. The CR was greater in athletes who reported COVID-19 (CR=74.4/1000 athletes/year, 95% CI 49.6 to 99.3) compared with those who did not (CR=17.2, 95% CI 16.3 to 18.2). Athletes with recent COVID-19 had a threefold higher rate of concussion (RR=3.1, 95% CI 2.0 to 4.7). CONCLUSION: Athletes returning from COVID-19 had higher CRs than those who did not experience COVID-19. This may be related to ongoing COVID-19 sequelae or deconditioning related to reduced training and competition load during the illness and when returning to sport. Further research is needed to understand the association of recent COVID-19 infection and concussion in order to inform preventive strategies.

Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe.

Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma.Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions.Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients.Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .

Influence of High School Socioeconomic Status on Athlete Injuries during the COVID-19 Pandemic: An Ecological Study.

Background: It is presently unclear how the cessation of high school sport has affected injury incidence at different socioeconomic levels. The COVID-19 pandemic may have disproportionately affected athletes of lower socioeconomic status, potentially increasing injury risk in this population. Purpose: To 1) Describe athlete injury incidence prior to and during the 2019-2020 and 2020-2021 school years in high school athletes by socioeconomic status; 2) Investigate the association between socioeconomic status and injury incidence in high school athletes. Study Design: Ecological Study. Methods: High schools were matched between the 2019-2020 and 2020-2021 school years. All athletes from all sports were included. High school socioeconomic status was determined by the school district median household income. Socioeconomic strata were defined as <$30,000, $30,000-50,000, $50,001-100,000, and >$100,000. Injury incidence proportion with 95% confidence interval (95% CI) was calculated for each academic year. Mixed effects negative binomial models with robust errors were performed to assess the association between the incidence proportion ratio and high school median household income. Six states and 176 high schools were included (2019-2020: 98,487 athletes; 2020-2021: 72,521 athletes). Results: Injury incidence increased in three of four socioeconomic strata during the 2020-2021 year (<$30,000: 2019-2020: 15.6 (13.1-18.1), 2020-2021: 26.3 (23.1-29.6); $30,000-50,000: 2019-2020: 7.8 (7.1-8.6), 2020-2021: 14.9 (13.8-15.9); $50,001-100,000: 2019-2020: 15.1 (14.7-15.4), 2020-2021: 21.3 (20.9-21.8); >$100,000: 2019-2020: 18.4 (18.1-18.8), 2020-2021: 17.3 (16.8-17.7)). An association was observed between injury incidence ratio and log median high school household income in 2019-2020 [1.6 (1.1-2.5)] but not 2020-2021 [1.1 (0.8-1.6)] school years. Conclusions: Athletes from lower socioeconomic high schools reported increased injury incidence compared to higher socioeconomic high schools during the 2020-2021 academic school year. These results highlight the increased COVID-19 pandemic vulnerability in athletes from lower socioeconomic high schools. High school sport stakeholders should consider how abrupt sport stoppage can affect lower socioeconomic athletes. Level of Evidence: 2.

Genetic risk and incident venous thromboembolism in middle-aged and older adults following COVID-19 vaccination.

BACKGROUND: COVID-19 vaccination has been associated with increased venous thromboembolism (VTE) risk. However, it is unknown whether genetic predisposition to VTE is associated with an increased risk of thrombosis following vaccination. METHODS: Using data from the UK Biobank, which contains in-depth genotyping and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants. We prospectively assessed associations between PRS and incident VTE immediately after first- and the second-dose vaccination and among historical unvaccinated cohorts during the pre- and early pandemic. We estimated hazard ratios (HR) for PRS-VTE associations using Cox models. RESULTS: Of 359 310 individuals receiving one dose of a COVID-19 vaccine, 160 327 (44.6%) were males, and the mean age at the vaccination date was 69.05 (standard deviation [SD] 8.04) years. After 28- and 90-days' follow-up, 88 and 299 individuals developed VTE, respectively, equivalent to an incidence rate of 0.88 (95% confidence interval [CI] 0.70-1.08) and 0.92 (0.82-1.04) per 100 000 person-days. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (1.15-1.73) in 28 days and 1.36 (1.22-1.52) in 90 days). Similar associations were found in the historical unvaccinated cohorts. CONCLUSIONS: The strength of genetic susceptibility with post-COVID-19-vaccination VTE is similar to that seen in historical data. Additionally, the observed PRS-VTE associations were equivalent for adenovirus- and mRNA-based vaccines. These findings suggest that, at the population level, the VTE that occurred after the COVID-19 vaccination has a similar genetic etiology to the conventional VTE.

Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19.

Importance: The risk of venous thromboembolism (VTE) in ambulatory COVID-19 is controversial. In addition, the association of vaccination with COVID-19-related VTE and relevant clinical and genetic risk factors remain to be elucidated. Objective: To quantify the association between ambulatory COVID-19 and short-term risk of VTE, study the potential protective role of vaccination, and investigate clinical and genetic risk factors for post-COVID-19 VTE. Design, Setting, and Participants: This population-based cohort study of patients with COVID-19 from UK Biobank included participants with SARS-CoV-2 infection that was confirmed by a positive polymerase chain test reaction result between March 1, 2020, and September 3, 2021, who were then propensity score matched to COVID-19-naive people during the same period. Participants with a history of VTE who used antithrombotic drugs (1 year before index dates) or tested positive in hospital were excluded. Exposures: First infection with SARS-CoV-2, age, sex, ethnicity, socioeconomic status, obesity, vaccination status, and inherited thrombophilia. Main Outcomes and Measures: The primary outcome was a composite VTE, including deep vein thrombosis or pulmonary embolism, which occurred 30 days after the infection. Hazard ratios (HRs) with 95% CIs were calculated using cause-specific Cox models. Results: In 18 818 outpatients with COVID-19 (10 580 women [56.2%]; mean [SD] age, 64.3 [8.0] years) and 93 179 matched uninfected participants (52 177 women [56.0%]; mean [SD] age, 64.3 [7.9] years), the infection was associated with an increased risk of VTE in 30 days (incidence rate of 50.99 and 2.37 per 1000 person-years for infected and uninfected people, respectively; HR, 21.42; 95% CI, 12.63-36.31). However, risk was substantially attenuated among the fully vaccinated (HR, 5.95; 95% CI, 1.82-19.5; interaction P = .02). In patients with COVID-19, older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 1.87 (95% CI, 1.50-2.33) per 10 years, 1.69 (95% CI, 1.30-2.19), and 1.83 (95% CI, 1.28-2.61), respectively. Further, inherited thrombophilia was associated with an HR of 2.05 (95% CI, 1.15-3.66) for post-COVID-19 VTE. Conclusions and Relevance: In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.

Subsequent Musculoskeletal Injury Incidence Are Similar Between General Infection and COVID-19 Among High School Athletes in the Unites States Despite Higher Illness Incidence During Academic Years 2019-2020 and 2020-2021.

OBJECTIVES: To describe overall illness and COVID-19- specific illness in high school athletes in the 2019-2020 and 2020-2021 academic school years, and to describe and assess the risk of musculoskeletal injury following general infection and after COVID-19. DESIGN: Ecological study. METHODS: High schools (6 states; 176 high schools) were matched between the 2019-2020 and 2020-2021 academic school years, based on 2020-2021 high school sport participation. Illness and injury data were collected from the high school athletic trainers. Illness was stratified by overall illness, general infection, and COVID-19. Injuries following moderate or severe infections or COVID-19 were recorded. Illness and injury incidence rate per 100 athletes per year, with 95% confidence intervals (95% CIs), were calculated. Negative binomial models comparing injury following general infections and COVID-19 infections were calculated. RESULTS: A total of 98 487 and 72 521 athletes participated in the 2019-2020 and 2020-2021 years. Illness incidence rate was less in the 2019-2020 academic school year [0.30 (95% CI: 0.27, 0.34)] than the 2020-2021 academic school year [1.1 (1.0-1.2)], resulting in a difference of 0.8 (95% CI: 0.7, 0.9). COVID-19 incidence rate was 0.52 (0.47-0.58) in the 2020-2021 year. Injury following general infection incidence rate was 27.9 injuries (21.4-34.5) per 100 athletes in 2019-2020, and 22.5 injuries (19.3-25.7) per 100 athletes in 2020-2021. There was no difference in injury risk following general infection and COVID-19 [rate ratio: 1.2 (95% CI: 0.7, 2.4)]. CONCLUSIONS: The incidence rate for all illnesses in high school athletes was slightly (0.8) greater in the 2020-2021 academic compared to the 2019-2020 year. Most of the incidence increase was due to infections and COVID-19. Subsequent injury incidence following moderate and severe infections were similar between years and between general infections and COVID-19. J Orthop Sports Phys Ther 2022;52(8):546-553. Epub: 19 June 2022. doi:10.2519/jospt.2022.11200.

The Impact of Statewide Limitations of Practice on High School Injury Incidence During the COVID-19 Season: An Ecological Study.

BACKGROUND: Abrupt training stoppage can increase injury incidence and risk following return to sport. The rate of coronavirus disease 2019 (COVID-19) infections in the general population has resulted in the abrupt stoppage of high school education and sport. The objective of this study was to (1) compare injury incidence proportion (IP) and excess injury in high school athletes before and during the COVID-19 pandemic; and (2) stratify by identified gender. HYPOTHESIS: The COVID-19 academic year will demonstrate increased injury incidence, and injury incidence will be similar between genders. STUDY DESIGN: Ecological. LEVEL OF EVIDENCE: Level 2. METHODS: High schools (6 states; 176 high schools) were matched between prepandemic and pandemic years. Injury IP with 95% confidence interval (CI) was calculated. Interrupted time series models with robust errors were performed to assess the IP ratio and excess injury incidence between prepandemic and pandemic academic calendar years. RESULTS: A total of 98,487 athletes participated in high school sport in the prepandemic year and 72,521 athletes in the pandemic year; 15,477 injuries were reported in the prepandemic year compared with 14,057 injuries during the pandemic year. Injury IP (CI) was 15.7 (15.5-15.9) and 19.4 (19.1-19.7) for the prepandemic and pandemic years, respectively. Injury incidence ratio increased by 1.3 (1.2-1.5) between the prepandemic and pandemic years. Excess injuries were 1812 greater in the pandemic year compared with the prepandemic year. Female and male athlete incidence ratios were similar. CONCLUSION: Prolonged sport stoppage due to the COVID-19 pandemic resulted in increased injury incidence compared with the previous high school academic year. CLINICAL RELEVANCE: High school sports stakeholders should consider longer periods of ramp up for training in lieu of future sport stoppages compared with usual preseason training. These data may also have more generalizable implications to other abrupt sport and physical activity stoppage scenarios such as earthquakes and hurricanes.

Development and external validation of prediction models for adverse health outcomes in rheumatoid arthritis: A multinational real-world cohort analysis.

BACKGROUND: Identification of rheumatoid arthritis (RA) patients at high risk of adverse health outcomes remains a major challenge. We aimed to develop and validate prediction models for a variety of adverse health outcomes in RA patients initiating first-line methotrexate (MTX) monotherapy. METHODS: Data from 15 claims and electronic health record databases across 9 countries were used. Models were developed and internally validated on Optum® De-identified Clinformatics® Data Mart Database using L1-regularized logistic regression to estimate the risk of adverse health outcomes within 3 months (leukopenia, pancytopenia, infection), 2 years (myocardial infarction (MI) and stroke), and 5 years (cancers [colorectal, breast, uterine] after treatment initiation. Candidate predictors included demographic variables and past medical history. Models were externally validated on all other databases. Performance was assessed using the area under the receiver operator characteristic curve (AUC) and calibration plots. FINDINGS: Models were developed and internally validated on 21,547 RA patients and externally validated on 131,928 RA patients. Models for serious infection (AUC: internal 0.74, external ranging from 0.62 to 0.83), MI (AUC: internal 0.76, external ranging from 0.56 to 0.82), and stroke (AUC: internal 0.77, external ranging from 0.63 to 0.95), showed good discrimination and adequate calibration. Models for the other outcomes showed modest internal discrimination (AUC < 0.65) and were not externally validated. INTERPRETATION: We developed and validated prediction models for a variety of adverse health outcomes in RA patients initiating first-line MTX monotherapy. Final models for serious infection, MI, and stroke demonstrated good performance across multiple databases and can be studied for clinical use. FUNDING: This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Comparative effectiveness of the BNT162b2 and ChAdOx1 vaccines against Covid-19 in people over 50.

Although pivotal trials with varying populations and study methods suggest higher efficacy for mRNA than adenoviral Covid-19 vaccines, not many studies have directly compared vaccine effectiveness in the population. Here, we conduct a head-to-head comparison of BNT162b2 versus ChAdOx1 against Covid-19. We analyse 235,181 UK Biobank participants aged 50 years or older and vaccinated with one or two doses of BNT162b2 or ChAdOx1. People are followed from the vaccination date until 18/10/2021. Inverse probability weighting is used to minimise confounding and the Cox models to derive hazard ratio. We find that, compared with one dose of ChAdOx1, vaccination with BNT162b2 is associated with a 28% (95% CI, 12-42) decreased risk of SARS-CoV-2 infection. Also, two doses of BNT162b2 vs ChAdOx1 confers 30% (95% CI, 25-35) and 29% (95% CI, 10-45) lower risks of both infection and hospitalisation during the study period when the Delta variant is dominant. Furthermore, the comparative protection against the infection persists for at least six months among the fully vaccinated, suggesting no differential waning between the two vaccines. These findings can inform evidence-based Covid-19 vaccination campaigns and booster strategies.

Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.

Purpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.

Fracturas de cadera en pacientes tratados con fármacos antipsicóticos. Estudio de cohortes históricas en Cataluña / Hip fractures in patients treated with antipsychotic drugs. Study of retrospective cohorts in Catalonia

Objetivo: Evaluar la incidencia de fractura de cadera en pacientes con tratamiento antipsicótico, comparándola con la de individuos que no han sido tratados con antipsicóticos.Diseño: Estudio de cohortes históricas de pacientes tratados con fármacos antipsicóticos (TAP) y pacientes sin tratamiento conocido (no TAP). El periodo de observación fue 2006-2014.Emplazamiento: Todos los equipos de atención primaria de Cataluña del Instituto Catalán de la Salud (ICS).Participantes: Pacientes mayores de 44 años con TAP de al menos 3 meses de duración. Cohorte control: selección aleatoria de pacientes no TAP emparejando por comorbilidades basales, sexo, edad y prescripción de fármacos (excluyendo psicofármacos). Se analiza un total de 22.010 pacientes.Mediciones principales Tasa de incidencia (×1.000 personas-año [PY]) de fractura de cadera en cada grupo (TAP y no TAP). Modelos de regresión de Cox para estimar riesgos ajustados (hazard ratio [HR]) añadiendo los psicofármacos como covariables. Resultados: La tasa de incidencia de fractura de cadera fue mayor en los pacientes TAP (5,83 frente a 3,58 fracturas por 1.000 PY), y es mayor en todos los estratos según sexo, edad y tipo de diagnóstico. El riesgo de sufrir una fractura de cadera fue un 60% mayor (HR: 1,60; IC95%: 1,34-1,92) en el grupo TAP que en el grupo no TAP. El riesgo fue mayor en el grupo con esquizofrenia (HR: 3,57; IC95%: 1,75-7,30), seguido del trastorno bipolar (HR: 2,61; IC95%: 1,39-4,92) y depresión (HR: 1,51; IC95%: 1,21-1,88). Conclusiones: Los pacientes con tratamiento antipsicótico presentan más riesgo de fractura de cadera que los que no han sido tratados con antipsicóticos.

ObjectiveTo evaluate the incidence of hip fracture in patients with antipsychotic treatment, comparing it with that of individuals who have not been treated with antipsychotics.DesignRetrospective cohort study of patients treated with antipsychotic drugs (TAP) and patients without known treatment (non-TAP). The observation period was 2006–2014.SiteAll primary care teams in Catalonia of the Catalan Health Institute (ICS).ParticipantsPatients older than 44 years with TAP lasting at least 3 months. Control cohort: random selection of non-TAP patients matching for baseline comorbidities and other variables. A total of 22,010 are analyzed.Main measurements Incidence rate (1000× person-years: PY) of hip fracture in each group (TAP and non-TAP). Cox regression models to estimate adjusted risks (hazard ratio: HR).ResultsThe hip fracture incidence rate was higher in TAP patients (5.83 vs 3.58 fractures per 1000 PY), and is higher in all strata according to sex, age and type of diagnosis. The risk of suffering a hip fracture was 60% higher (HR: 1.60 95% CI: 1.34–1.92) in the TAP group than in the non-TAP group. The risk was higher in the group with schizophrenia (HR: 3.57 95% CI: 1.75–7.30), followed by bipolar disorder (HR: 2.61; 95% CI: 1.39–4.92) and depression (HR: 1.51; 95% CI: 1.21–1.88).ConclusionsPatients with antipsychotic treatment have a higher risk of hip fracture than those who have not been treated with antipsychotics.