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Background: Studies suggest that depression/anxiety form part of the multiple sclerosis (MS) prodrome. However, several biases have not been addressed. We re-examined this association after correcting for: (i) misclassification of individuals not seeking healthcare, (ii) differential surveillance of depression/anxiety in the health system, and (iii) misclassified person-time from using the date of the first MS-related diagnostic claim (i.e., a demyelinating event) as a proxy for MS onset., Methods: In this cohort study, we applied a validated algorithm to health administrative ('claims') data in British Columbia, Canada (1991-2020) to identify MS cases, and matched to general population controls. The neurologist-recorded date of MS symptom onset was available for a subset of the MS cases. We identified depression/anxiety in the 5-years preceding the first demyelinating claim using a validated algorithm. We compared the prevalence of depression/anxiety using modified Poisson regression. To account for misclassification and differential surveillance, we applied probabilistic bias analyses; for misclassified person-time, we applied time-distribution matching to the MS symptom onset date., Results: Our cohort included 9929 MS cases and 49,574 controls. The prevalence ratio for depression/anxiety was 1.74 (95 %CI: 1.66-1.81). Following correction for misclassification, differential surveillance using a detection ratio of 1.11, and misclassified person-time, the prevalence ratio increased to 3.25 (95 %CI: 1.98-40.54). When the same correction was conducted, but a detection ratio of 1.16 was applied, the prevalence ratio increased to 3.13 (95 %CI: 1.97-33.52)., Conclusions: Previous conventional analyses were biased towards the null, leading to an under-estimation of the association between depression/anxiety and MS in the prodromal period. This first application of probabilistic quantitative bias analysis within MS research demonstrates both its feasibility and utility., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fardowsa Yusuf reports financial support was provided by The Canadian Institutes of Health Research. Helen Tremlett reports financial support was provided by National Multiple Sclerosis Society. Helen Tremlett reports financial support was provided by MS Canada. Jason M Sutherland, Paul Gustafson, Feng Zhu and Yinshan Zhao report no disclosures. Fardowsa Yusuf is funded by a Fredrick Banting and Charles Best Canada Graduate Scholarship from the Canadian Institutes of Health Research (CIHR). The Michael Smith Health Research BC Scholar Award has provided support to Mohammad Ehsanul Karim. In the previous three years, MEK has received consulting fees from Biogen Inc. for consulting work that is not related to the current project. MEK’s research is backed by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (PG#: 20R01603) and Discovery Launch Supplement (PG#: 20R12709). Ruth Ann Marrie receives research funding from: CIHR, Research Manitoba, MS Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC. She is supported by the Waugh Family Chair in Multiple Sclerosis. She is a co-investigator on studies funded partly by Biogen Idec and Roche (no funds to her, her institution). Helen Tremlett has, in the last five years, received research support from the Canada Research Chair Program, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada, the Multiple Sclerosis Scientific Research Foundation and the EDMUS Foundation (‘Fondation EDMUS contre la sclérose en plaques’). In addition, in the last five years, has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences from the Consortium of MS Centres (2018, 2023), National MS Society (2018, 2022), ECTRIMS/ ACTRIMS (2017–2023), American Academy of Neurology (2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by HT’s research group. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: to directly compare the risk of neonatal death between traditional birth attendant (TBA)-assisted and unassisted deliveries in Nigeria., Methods: Using data on live births from the 2008, 2013, and 2018 Nigeria Demographic and Health Surveys, this cross-sectional study compared risk of neonatal death for TBA-assisted versus unassisted births. We used survey-featured logistic regression to estimate the odds of neonatal death. Survey year-stratified and propensity score-matched (PSM) estimates were obtained. Multivariate imputation by chained equation (MICE) for missing data was conducted., Results: A total of 28, 922 births were included. Regression and PSM analysis of pooled data showed that unassisted births had lower odds of neonatal death compared to TBA-assisted births, (aOR 0.81, 95% CI: 0.65,1.00) and (aOR 0.80, 95% CI: 0.64,1.00), respectively. Regression analysis by survey year yielded non-significant higher odds of neonatal death for TBA-assisted births. Pooled estimates from MICE showed non-significant higher odds of death for TBA-assisted births., Conclusions: These findings indicate that birth care by TBAs do not necessarily lead to better neonatal survival. Jurisdictions seeking to allow continued operation of TBAs need to consider measures such as training, supervision, and regulation to ensure the safety of newborns., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To explore the rheumatoid arthritis (RA)-cardiovascular diseases (CVD) association in relative and absolute risk scales among US adults aged ≥20 years over time and the effect modification of the association by age., Methods: We analyzed aggregated data from all ten continuous National Health and Nutrition Examination Survey cycles. A sample of 35,062 complete-case subjects was considered. The design-based regressions were used to investigate the associations in relative and absolute scales., Results: In relative scale, the CVD odds ratio was 2.32, 2.19, and 1.97 among adults with RA than no arthritis in 1999-2006, 2007-2012, and 2013-2018 cycles, respectively. This time trend was not statistically significant. The absolute risk estimates were 11, 10, and 9 per 100 CVD events. We also observed a significant effect modification by age; the higher relative risk among younger adults (<50 years) with RA and higher absolute risk in older adults (≥80 years) with RA were consistent across survey cycles., Conclusions: There is a significant association between RA and CVD among US adults in both relative and absolute risks. Moreover, age is a significant effect modifier for this association; but with opposing age-related trends in relative and absolute scales., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To examine the association between diabetes and excessive daytime sleepiness (EDS)., Methods: Using the 2015-2018 cycles of the National Health and Nutrition Examination Survey, we applied survey-featured modified Poisson regression to estimate the association between diabetes and EDS among American adults aged 20-79 years, adjusting for confounding demographic, clinical and lifestyle variables. Effect modification by age, sex, race, education, income, sleep apnea and inadequate sleep was assessed. We performed sensitivity analyses using propensity score matched (PS) data and applied ordinal logistic regression using multiple levels of daytime sleepiness. Among people with diabetes, we assessed the association between EDS and diabetes care variables., Results: Of the 6289 participants, 895 (10%) had diabetes. The estimated prevalence of EDS was higher among adults with diabetes (30.6%) than counterparts without diabetes (26.3%). After adjusting for confounding variables, diabetes remained associated with EDS (aPR:1.20; 95%CI:1.06 1.36). There was no statistically significant effect modification. Sensitivity analyses confirmed our main results. Among people with diabetes, there was limited evidence that the diabetes care variables were related to EDS., Conclusions: Among American adults, diabetes is associated with EDS after controlling for confounding variables. Although the cross-sectional design is a limitation, our findings support further exploration of the role of diabetes in EDS., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Unmeasured confounding poses a serious threat to observational studies of post-TB health outcomes. E-values have been recently proposed as a method to assess the magnitude of unmeasured confounding necessary to nullify, or to render non-significant, relative effect estimates from observational studies., Methods: We calculated E-values for both the risk ratio (RR) point estimates and their lower 95% confidence limits (LCL) from studies of post-TB mortality, respiratory disease, and cardiovascular disease (CVD) included in published systematic reviews within and across post-TB outcome domains. We also employed a meta-analytic E-value approach to estimate the proportion of unconfounded study RRs greater than 1.1 at different levels of unmeasured confounding., Results: Across post-TB health outcome domains, we observed a median E-value of 5.59 (IQR = 3.19-7.35) for RRs, and 2.95 (IQR = 1.71-4.61) for LCLs. Post-TB mortality studies had higher median E-values (E-value RR  = 6.90 and E-value LCL  = 4.54) than studies of respiratory disease (E-value RR  = 5.59, E-value LCL  = 2.94) or CVD (E-value RR  = 3.90, E-value LCL  = 1.81). The E-value at which the estimated proportion of studies with unconfounded RRs greater than 1.1 would remain over 0.7 was 3.45 for post-TB mortality, 3.96 for post-TB respiratory disease, and 1.71 for post-TB CVD meta-analyses., Conclusions: Unmeasured confounding with an association of 2.95 or greater with both the exposure (TB) and outcome, on the risk ratio scale, could render most post-TB health studies' findings statistically non-significant. Post-TB mortality and respiratory disease studies had higher E-values than TB-CVD studies, indicating that either (a) TB-CVD studies may be more susceptible to unmeasured confounding bias, or (b) the true effect of TB on CVD is lower., Competing Interests: Declaration of Competing Interest CAB declares no conflicts or competing interests. MEK has received consulting fees from Biogen, Inc., unrelated to this manuscript., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To estimate the risk of tuberculosis (TB)-associated depression. A second aim was to estimate the extent to which any increased risk of depression among TB patients may be mediated by the length of hospital length stay (LOS) METHODS: Retrospective cohort study of linked healthcare claims and public health surveillance data. Our primary outcome, time-to-depression, was analyzed using Cox proportional hazards (PH) regressions. Causal mediation analysis was used to estimate the natural direct and indirect effect of TB mediated by hospital LOS., Results: Among 755,836 participants (52.2% female, median age=35 years, median follow-up=8.75 years), 2295 were diagnosed with TB (exposure), and 128,963 were diagnosed with depression (outcome). We observed a covariate-adjusted hazard ratio (aHR) of 1.24 (95% CI, 1.14-1.34) for depression by TB. The total effect of TB on depression was decomposed into a natural direct effect of TB of aHR=1.11 (95% CI, 1.02-1.21) and an indirect effect through hospital LOS of aHR=1.11 (95% CI, 1.10-1.12), indicating that TB's total effect was mediated by 50% (95% CI, 35-82%) through hospital LOS., Conclusions: TB patients had a 24% higher risk of developing depression. TB's effect was mediated substantially by hospital LOS, requiring further study. Depression screening among TB patients is warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)