OBJECTIVE:This study describes the enrollment and baseline characteristics of participants in the Lumbar Stenosis Prognostic Subgroups for Personalizing Care and Treatment Study (PROSPECTS) cohort and explores subgroups of patients presenting for nonoperative care. DESIGN:Cross-sectional study. SETTING AND SUBJECTS:We enrolled adults ≥50 years of age initiating nonoperative care for symptomatic lumbar spinal stenosis. We excluded those with serious spinal pathology, conditions limiting ambulation, and prior or planned lumbar surgery. METHODS:We collected demographics, the Patient-Reported Outcomes Measurement Information System (PROMIS) 29, pain intensity, Oswestry Disability Index, Swiss Spinal Stenosis Questionnaire, chronicity of symptoms, pain sites, comorbidities, falls, and opioid use. We used descriptive statistics to characterize the sample and latent class analysis to derive subgroups with distinct phenotypes. The best model was selected on the basis of model fit statistics, class separation, and clinical interpretability. RESULTS:We enrolled 598 participants. The mean age was 67 (SD = 9), and 61% were female. Back and leg pain had been present for ≥1 year in 65% of participants. Multiple pain sites were common, with a mean of 4.3 sites (SD = 2.2), and a majority of patients had multiple comorbidities (54%). We selected a 4-class solution as the best model from the latent class analysis. These phenotypes were described as (1) "high pain impact, low psychosocial features" (n = 233; 39%), (2) "mild pain impact, low psychosocial features" (n = 218; 36%), (3) "high pain impact, complex health needs" (n = 95; 16%), and (4) "acute, intermittent, moderate-severe leg pain with high pain impact" (n = 52; 9%). CONCLUSIONS:These phenotypes reflect distinct profiles that could inform health needs and patient-centered care. Future studies should examine longitudinal outcomes to establish their clinical utility and prognostic value.
Background New respiratory syncytial virus (RSV) vaccines have been approved in the USA for the prevention of RSV-associated lower respiratory tract disease in adults aged 60 years and older. Information on the real-world effectiveness of these vaccines is needed. Methods We used electronic health records in the Veterans Health Administration to emulate a target trial comparing a single dose of a recombinant stabilised prefusion F protein RSV vaccine versus no vaccination among veterans aged 60 years and older. We matched eligible vaccine recipients with up to four unvaccinated individuals in four monthly nested sequential trials from Sept 1 to Dec 31, 2023. Outcomes were ascertained up to March 31, 2024. The primary outcome was any positive RSV test from day 14 following the matched index date. Secondary outcomes included hospitalisation and emergency department or urgent care encounter occurring within 1 day before or after a positive RSV test. We estimated vaccine effectiveness as 100 x (1-risk ratio). Findings We included 146 852 vaccinated individuals matched to 582 936 unique control individuals, weighted equally to represent 146 852 individuals. Across the two groups, 276 039 (940%) of 293 704 veterans were male, 17 665 (60%) were female, and median age was 759 years (IQR 717-797). Over a median follow-up of 124 days (IQR 102-150), the incidence rate of documented RSV infection was 17 (95% CI 14-21) events per 1000 person-years (88 total events) in the vaccinated group and 73 (66-81) per 1000 person-years in the unvaccinated group (372 total events), and vaccine effectiveness was estimated as 781% (726-835). Among the secondary outcomes, vaccine effectiveness was estimated at 787% (722-848) against RSV-associated emergency department or urgent care encounters, and 803% (658-901) against RSV-associated hospitalisation. Interpretation RSV vaccination was effective in preventing RSV-related illness, including associated health-care use, in adults aged 60 years and older during the 2023-24 respiratory illness season, supporting current recommendations for vaccination in this population.
Introduction:Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.Objectives:We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.Methods:Using phenotypes and imputed genotypes from the UK Biobank 500k dataset, we generated a multi-trait phenotype by combining 3 BP-related phenotypes: chronic BP, dorsalgia, and intervertebral disk disorders. We performed gene-based association analysis for 3 BP-related phenotypes and multi-trait phenotype. Conditional analysis was applied to account for the effects of genetic variants outside the gene. Finally, we replicated significantly associated genes using the FinnGen database.Results:We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported. Several new genes are known to be associated with traits genetically correlated with BP or to be involved in pathways associated with BP.Conclusion:Using new powerful methods of association analysis, we identified 7 novel genes associated with BP. Our results provide new insights into the genetics of back pain.
BACKGROUND:Monovalent COVID-19 vaccines targeting the XBB.1.5 Omicron variant were introduced in September 2023. In the absence of randomized controlled trials demonstrating their efficacy, information on real-world vaccine effectiveness (VE) is needed. OBJECTIVE:To determine XBB.1.5 COVID-19 VE and the extent to which it declines over time. DESIGN:Target trial emulation. SETTING:U.S. Veterans Health Administration. PARTICIPANTS:Eligible XBB.1.5 vaccine recipients were matched 1:1 to unvaccinated persons in 7 sequential biweekly trials with enrollment from 2 October 2023 through 3 January 2024. INTERVENTION:XBB.1.5 COVID-19 vaccination versus no XBB.1.5 vaccination. MEASUREMENTS:Outcomes were ascertained through 10 May 2024 and included any positive result on a SARS-CoV-2 test from day 10 after the matched index date, subsequent hospitalization within 1 day before or 10 days after the positive result, or death within 30 days after the positive result. Vaccine effectiveness was estimated as 100 × (1 - risk ratio). RESULTS:Participants (91.3% male; mean age, 69.9 years) included 587 137 pairs of vaccinated and matched unvaccinated persons. Over a mean follow-up of 176 days (range, 118 to 211 days), VE was -3.26% (95% CI, -6.78% to -0.22%) against documented SARS-CoV-2 infection, 16.64% (CI, 6.47% to 25.77%) against SARS-CoV-2-associated hospitalization, and 26.61% (CI, 5.53% to 42.32%) against SARS-CoV-2-associated death. When estimated at 60, 90, and 120 days, respectively, VE against documented infection (14.21%, 7.29%, and 3.15%), hospitalization (37.57%, 30.84%, and 25.25%), or death (54.24%, 44.33%, and 30.25%) showed substantial waning. LIMITATION:Potential for residual confounding and incomplete capture of COVID-19 vaccination and SARS-CoV-2-related outcomes. CONCLUSION:COVID-19 vaccines targeting the XBB.1.5 variant of Omicron were not effective in preventing infection and had relatively low VE against hospitalization and death, which declined rapidly over time. PRIMARY FUNDING SOURCE:U.S. Department of Veterans Affairs.
Rationale: The prevalence of chronic respiratory disease is increased among Veterans returning from deployments to southwest Asia. Blast exposure during military deployment is common and has been proposed as a risk factor for respiratory symptoms. Methods: Using data from the multicenter Veterans Affairs Cooperative Studies Program #595, Service and Health Among Deployed Veterans (SHADE), we examined the association between blast exposures during deployment and respiratory symptoms post-deployment. Participants were randomly selected from deployment roster records and characteristics were measured at enrollment into the cohort. Blast exposure from an improvised explosive device or other explosion was self-reported using a coordinator-administered survey that included blast proximity (<30 feet) and an estimate of blast exposure frequency. Chronic bronchitis, wheeze (in the past 12 months), and dyspnea (other than with heavy exertion) were defined by established questionnaire items. Occupational and environmental deployment-related exposure to burn pits and vapor, gas, dusts, and fumes (VGDF) were quantified through a validated instrument. After adjusting for potential confounders including age, sex, race (black, white, other), and body mass index, we used multivariable hierarchical logistic models with Kenward-Roger degrees of freedom estimation to estimate the associations between blast exposure and respiratory symptoms. We created additional models including smoking status (current, former, never) and deployment-related exposures domains with known association with respiratory symptoms (burn pits and VGDF). Results: Of the 1,958 study participants, 88% were male and 963 (49.2%) reported being exposed to blasts during their deployment. 65% were <30 ft and the median frequency of blast exposure was 3 (IQR 1 to 10). Respiratory symptoms were assessed a mean (SD) 10.1 (3.6) years post-deployment. Compared to participants without any blast exposure, those with blast exposure were more frequently male, in the Army (vs. Marines or Air Force) and had longer duration of deployment. After adjusting for demographic and smoking, blast exposure was statistically significantly associated with increased odds of dyspnea, but not wheeze or chronic bronchitis (Table). After further adjustment for burn pit and VGDF exposures, the odds of dyspnea were attenuated (OR 1.46; 95% CI: 0.97 to 2.19). Conclusions: Self-reported blast exposures were highly prevalent and associated with dyspnea, however the association was attenuated after adjusting for selected deployment-related occupational/environmental exposures. Our results suggest that comprehensive assessment of exposures is needed to assess health effects after blast exposures, including possible effects of co-exposures.
