Risk of carpal tunnel syndrome among patients with osteoarthritis: a US population-based study.

BACKGROUND: Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. METHODS: Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. RESULTS: After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21-7.49) in the OA cohort and 1.44 (95% CI 1.38-1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54-4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. CONCLUSIONS: OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS.

Association of Remdesivir Treatment With Mortality Among Hospitalized Adults With COVID-19 in the United States.

Importance: SARS-CoV-2, which causes COVID-19, poses considerable morbidity and mortality risks. Studies using data collected during routine clinical practice can supplement randomized clinical trials to provide needed evidence, especially during a global pandemic, and can yield markedly larger sample sizes to assess outcomes for important patient subgroups. Objective: To evaluate the association of remdesivir treatment with inpatient mortality among patients with COVID-19 outside of the clinical trial setting. Design, Setting, and Participants: A retrospective cohort study in US hospitals using health insurance claims data linked to hospital chargemaster data from December 1, 2018, to May 3, 2021, was conducted among 24 856 adults hospitalized between May 1, 2020, and May 3, 2021, with newly diagnosed COVID-19 who received remdesivir and 24 856 propensity score-matched control patients. Exposure: Remdesivir treatment. Main Outcomes and Measures: All-cause inpatient mortality within 28 days of the start of remdesivir treatment for the remdesivir-exposed group or the matched index date for the control group. Results: A total of 24 856 remdesivir-exposed patients (12 596 men [50.7%]; mean [SD] age, 66.8 [15.4] years) and 24 856 propensity score-matched control patients (12 621 men [50.8%]; mean [SD] age, 66.8 [15.4] years) were included in the study. Median follow-up was 6 days (IQR, 4-11 days) in the remdesivir group and 5 days (IQR, 2-10 days) in the control group. There were 3557 mortality events (14.3%) in the remdesivir group and 3775 mortality events (15.2%) in the control group. The 28-day mortality rate was 0.5 per person-month in the remdesivir group and 0.6 per person-month in the control group. Remdesivir treatment was associated with a statistically significant 17% reduction in inpatient mortality among patients hospitalized with COVID-19 compared with propensity score-matched control patients (hazard ratio, 0.83 [95% CI, 0.79-0.87]). Conclusions and Relevance: In this retrospective cohort study using health insurance claims and hospital chargemaster data, remdesivir treatment was associated with a significantly reduced inpatient mortality overall among patients hospitalized with COVID-19. Results of this analysis using data collected during routine clinical practice and state-of-the-art methods complement results from randomized clinical trials. Future areas of research include assessing the association of remdesivir treatment with inpatient mortality during the circulation of different variants and relative to time from symptom onset.

Real-World Evidence of Axicabtagene Ciloleucel for the Treatment of Large B Cell Lymphoma in the United States.

Axicabtagene ciloleucel (axi-cel) is a standard-of-care for patients with relapsed or refractory (r/r) large B cell lymphoma who have received 2 or more lines of prior therapy. Patients receiving axi-cel in the real world could have broader a demographic, disease, and treatment profile compared with that of the cohort in the pivotal ZUMA-1 trial. The present study was conducted to evaluate the outcomes of axi-cel therapy in the real-world setting. A total of 1297 patients receiving commercial axi-cel between 2017 and 2020 were selected from the Center for International Blood and Marrow Transplant Research's data registry, of whom 739 (57%) would have been ineligible for inclusion in the ZUMA-1 cohort. Efficacy and safety outcomes were described for the entire cohort and by ZUMA-1 eligibility. Their associations with age, Eastern Cooperative Oncology Group Performance Score, and comorbidities were evaluated using multivariable logistic and Cox regressions. At a median follow-up of 12.9 months, the overall response rate (ORR) was 73%, with a 56% complete response (CR) rate. Median overall survival (OS) and progression-free survival (PFS) were 21.8 months (95% confidence interval [CI], 17.4 to 28.8 months) and 8.6 months (95% CI, 6.5 to 12.1 months), respectively. Duration of response (DOR) was comparable in the ZUMA-1 ineligible patients and ZUMA-1 eligible patients (62% by 1 year [95% CI, 57% to 66%] versus 67% [95% CI, 62% to 72%]). Patients age ≥65 years had favorable ORR (odds ratio [OR], 1.39; 95% CI, 1.05 to 1.83) despite having a higher risk of cytokine release syndrome (CRS) (OR, 1.41; 95% CI, 1.02 to 1.94) and immune effector cell-associated neurotoxicity syndrome (ICANS) (OR, 1.77; 95% CI, 1.39-2.26). Eastern Cooperative Oncology Group Performance Score ≥2 was associated with inferior efficacy outcomes (OR for ORR, 0.32; 95% CI, 0.18-0.56; hazard ratio [HR] for OS, 3.27; 95% CI, 2.37 to 4.52) and higher incidence of ICANS (OR, 2.63; 95% CI, 1.40 to 4.93). The patients ineligible for ZUMA-1 still had a durable response with axi-cel. Elderly patients had favorable efficacy outcomes despite higher rates of CRS and ICANS. Patient selection for standard-of-care axi-cel should consider comorbidities and risk-to-benefit ratio rather than be based strictly on ZUMA-1 eligibility.

COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Estimation of new HIV diagnosis rates among high-risk, PrEP-eligible individuals using HIV surveillance data at the Metropolitan Statistical Area level in the United States.

INTRODUCTION: New HIV diagnoses have fallen in the past decade due to increased HIV testing, earlier diagnosis, earlier antiretroviral treatment, improved linkage to care and engagement in care, and the recent increased uptake of pre-exposure prophylaxis (PrEP). We propose a novel method to compute the rate of new HIV diagnoses at the Metropolitan Statistical Area (MSA) level in the US to support the evaluation of comprehensive treatment and prevention efforts over time. METHODS: The number of new HIV diagnoses, number of individuals with a PrEP indication and aggregated person-time exposed to PrEP during the years 2012 to 2017 were used to compute a new HIV diagnosis rate for people at risk of HIV excluding those already on PrEP for the 105 MSAs in the US with published HIV surveillance data. In our calculation of person-time with a PrEP indication, time-at-risk excluded time on PrEP and time after an HIV diagnosis. We used a multivariate Poisson regression model to estimate HIV diagnosis rates by year and location. RESULTS: From 2012 to 2017, the aggregate HIV diagnoses rate among high-risk individuals with an indication for PrEP in the 105 MSAs decreased from 4.14 per 100 person-years (PY) (95% CI 4.10 to 4.19) to 3.26 per 100 PY (95% CI 3.22 to 3.30). For the 25 US MSAs that overlapped with an ongoing large randomized clinical trial of PrEP in men who have sex with men (MSM), the HIV diagnosis rate from 2012 to 2017 decreased from 4.86 per 100 PY (95% CI 4.80 to 4.93) to 3.61 per 100 PY (95% CI 3.56 to 3.66), a decline that was more rapid than in non-study MSAs (IRR for trial site 1.19, 95% CI 1.18 to 1.20). CONCLUSIONS: We propose a model to estimate the background HIV diagnosis rate in people at risk for HIV and with a PrEP indication in US MSAs (excluding those on PrEP) using publically available surveillance data which can evaluate trends over time. Data generated using this methodology could be used by policy makers and local HIV prevention specialists to evaluate and monitor their prevention efforts for the population at risk in their communities.

Effects of an intensive behavioral weight loss intervention consisting of caloric restriction with or without physical activity on common carotid artery remodeling in severely obese adults.

OBJECTIVE: Obesity increases cardiovascular disease risk and adversely affects vascular structure and function. Few studies have evaluated the vascular effects of non-surgical weight reduction in the severely obese. We hypothesized that weight loss and improvements in cardiometabolic factors would reduce common carotid artery intima-media thickness (CIMT) and inter-adventitial diameter (AD) in severely obese adults. METHODS: We performed carotid ultrasound and measured cardiometabolic factors in 90 severely obese participants (body mass index (BMI)≥35 kg/m(2), age 30-55) at baseline and 6 months in a randomized clinical trial of dietary intervention with (n=45) or without (n=45) physical activity. RESULTS: The achieved weight loss (mean=8%) did not differ significantly by intervention group (P=0.10) and resulted in a 0.07 mm mean decrease in AD (P=0.001). AD change was positively correlated with changes in BMI, waist circumference, abdominal visceral and subcutaneous fat, and body fat mass, and AD decreased more in men (P<0.05 for all). After multivariable adjustment, changes in BMI (P=0.03) and abdominal subcutaneous fat (P=0.04) were significant determinants of AD change. Although CIMT did not decrease significantly overall (-0.008 mm, P=0.16), individuals who lost at least 5% of their body weight experienced a significant mean reduction in CIMT of 0.02 mm (P=0.002). CIMT change was positively correlated with changes in BMI, waist circumference, fat-free mass, leptin, and insulin (P<0.05 for all). After multivariable adjustment, insulin reduction remained a significant determinant of CIMT decrease (P=0.03). CONCLUSION: A 6 month intensive behavioral intervention can significantly reverse metabolic and vascular abnormalities in severely obese adults.