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Association of Daily Steps with Incident Non-Alcoholic Fatty Liver Disease: Evidence from the UK Biobank Cohort.
PURPOSE: Low physical activity has been shown to be associated with higher risk of non-alcoholic fatty liver disease (NAFLD). However, the strength and shape of this association are currently uncertain due to a reliance on self-reported physical activity measures. This report aims to investigate the relationship of median daily step count with NAFLD using accelerometer-derived step count from a large prospective cohort study. METHODS: The wrist-worn accelerometer sub-study of the UK Biobank (N = ~100,000) was used to characterise median daily step count over a seven-day period. NAFLD cases were ascertained via record linkage with hospital inpatient data and death registers or by using a measure of liver fat from imaging. Cox proportional hazards models were employed to assess the association between step count and NAFLD, adjusting for age, sociodemographic, and lifestyle factors. Mediation analyses were conducted. RESULTS: Among 91,031 participants (709,440 person-years of follow-up), there were 762 incident NAFLD cases. Higher step count was log-linearly and inversely associated with risk of NAFLD. A 1000-step increase (representing 10 minutes of walking) was associated with a 12% (95% CI: 10%-14%) lower hazard of NAFLD. When using imaging to identify NAFLD, a 1,000-step increase was associated with a 6% (95% CI: 6%-7%) lower risk. There was evidence for mediation by adiposity, accounting for 39% of the observed association. CONCLUSIONS: Daily step count, a modifiable risk factor, is log-linearly and inversely associated with NAFLD. This association was only partially explained by adiposity. These findings from a large cohort study may have important implications for strategies to lower NAFLD risk.
MSP-tracker: A versatile vesicle tracking software tool used to reveal the spatial control of polarized secretion in Drosophila epithelial cells.
Understanding how specific secretory cargoes are targeted to distinct domains of the plasma membrane in epithelial cells requires analyzing the trafficking of post-Golgi vesicles to their sites of secretion. We used the RUSH (retention using selective hooks) system to synchronously release an apical cargo, Cadherin 99C (Cad99C), and a basolateral cargo, the ECM protein Nidogen, from the endoplasmic reticulum and follow their movements to the plasma membrane. We also developed an interactive vesicle tracking framework, MSP-tracker and viewer, that exploits developments in computer vision and deep learning to determine vesicle trajectories in a noisy environment without the need for extensive training data. MSP-tracker outperformed other tracking software in detecting and tracking post-Golgi vesicles, revealing that Cad99c vesicles predominantly move apically with a mean speed of 1.1µm/sec. This is reduced to 0.85 µm/sec by a dominant slow dynein mutant, demonstrating that dynein transports Cad99C vesicles to the apical cortex. Furthermore, both the dynein mutant and microtubule depolymerization cause lateral Cad99C secretion. Thus, microtubule organization plays a central role in targeting apical secretion, suggesting that Drosophila does not have distinct apical versus basolateral vesicle fusion machinery. Nidogen vesicles undergo planar-polarized transport to the leading edge of follicle cells as they migrate over the ECM, whereas most Collagen is secreted at trailing edges. The follicle cells therefore bias secretion of different ECM components to opposite sides of the cell, revealing that the secretory pathway is more spatially organized than previously thought.
Using a Machine Learning Approach to Predict Snakebite Envenoming Outcomes Among Patients Attending the Snakebite Treatment and Research Hospital in Kaltungo, Northeastern Nigeria
The Snakebite Treatment and Research Hospital (SBTRH) is a leading centre for snakebite envenoming care and research in sub-Saharan Africa, treating over 2500 snakebite patients annually. Despite routine data collection, routine analyses are seldom conducted to identify trends or guide clinical practices. This study retrospectively analyzes 1022 snakebite cases at SBTRH from January to June 2024. Most patients were adults (62%) and were predominantly male (72%). Key factors such as age, sex, and time between bite and hospital presentation were associated with outcomes, including recovery, amputation, debridement, and death. Adult males who took more than four hours to arrive to hospital were identified as a high-risk group for poor outcomes. Using patient characteristics, an XGBoost model was developed and was compared to Random Forest and logistic regression models. In general, all models had high positive predictive value and low sensitivity, meaning that if they predicted a patient to experience amputation, debridement, or death, that patient almost always actually experienced amputation, debridement, or death; however, most models rarely made this prediction. The XGBoost model with all features was optimal, given that it had both a high positive predictive value and relatively high sensitivity. This may be of significance to resource-limited settings like SBTRH, where antivenoms can be scarce; however, more research is needed to build better predictive models. These findings underscore the need for targeted interventions for high-risk groups, and further research and integration of machine-learning-driven decision support tools in low-resource-limited clinical settings.
Prevalence of undiagnosed hypertension and associated factors in Ndera sector, Gasabo district of Rwanda: a cross-sectional study.
BackgroundHypertension remains a major global health challenge, including in low- and middle-income countries. In Rwanda, a lack of adequate information and healthcare services impacts healthcare-seeking behaviors, contributing to undiagnosed hypertension in rural areas. Therefore, the need to determine its prevalence and associated factors.MethodsA cross-sectional study was conducted with 393 adults in the Ndera Sector, of Rwanda's Gasabo District, through a multistage sampling technique. Data was gathered using the WHO STEP-wise approach to non-communicable disease risk factor surveillance (STEPS) questionnaire; physical examination was done to determine blood pressure and body-mass index (BMI), after which the data collected was analyzed using SPSS. Newly diagnosed hypertension was determined when on two different intervals, systolic blood pressure readings was > 140 mmHg, and/or the diastolic blood pressure readings was > 90 mmHg, in the absence of previous hypertension diagnosis.ResultsThe overall prevalence of hypertension among patients at Ndera sector was 15%, all of which were newly diagnosed. The mean (SD) age of the participants was 37 (13.7) years and half (53%) were women. The mean systolic blood pressure for men was 124.3 mmHg compared to 120.9 mmHg for women (p = 0.043, 95%CI: 0.12-6.74). Women had a significantly higher mean BMI (26.0) compared to men (22.8) (p ConclusionsThe high prevalence of undiagnosed hypertension in Ndera Sector is linked to gender, older age, higher BMI, location, and lack of hypertension knowledge. These findings call for multifaceted approaches, combining educational initiatives, geographical targeting, lifestyle modifications, and policy implementations, all aimed at mitigating the burden of undiagnosed hypertension and enhancing community health within the Ndera Sector.
Usefulness of MRI-Based Local Surveillance After Surgical Treatment of Musculoskeletal Soft-Tissue Sarcomas: A Systematic Review and Meta-Analysis.
BACKGROUND. The value of routine MRI follow-up after surgical treatment of musculoskeletal soft-tissue sarcoma (STS) is controversial. OBJECTIVE. The purpose of this study was to evaluate the usefulness of MRI-based surveillance for musculoskeletal STS represented by the proportion of local recurrences (LRs) discovered by MRI versus clinically, stratified by imaging surveillance intensity; the characteristics of LRs detected on imaging versus clinically; and the impact of imaging surveillance on survival. EVIDENCE ACQUISITION. Multiple electronic databases were searched systematically for articles published through November 28, 2022, about controlled trials and cohort studies on the usefulness of MRI-based surveillance for musculoskeletal STS. The risk of bias was assessed using an adapted Newcastle-Ottawa scale. Random-effects meta-analyses of the proportion of LRs discovered by MRI as opposed to clinically were conducted. The association of low- versus high-intensity surveillance with the proportion of LR detected on MRI was assessed with a chi-square test of subgroup differences; for this latter assessment, high intensity was defined as at least one local surveillance imaging examination for low-risk tumors and at least three imaging examinations for high-risk tumors during the first 2 posttreatment years. EVIDENCE SYNTHESIS. A total of 4821 titles and abstracts were identified, and 19 studies were included. All studies were retrospective cohorts. There was substantial variability in follow-up approaches. The risk of bias was moderate in 32% and high in 68% of studies. The pooled proportion of LRs detected on MRI was 53% (95% CI, 36-71%) with high-intensity surveillance and 6% (95% CI, 3-9%) with low-intensity surveillance (p < .01). Comparison of LR characteristics (LR size, depth, grade, location, resection margins) detected on imaging versus clinically identified inconsistent results between studies. Trends toward better survival for imaging-detected LRs or more frequent imaging use were noted in four studies. CONCLUSION. When used at a high intensity, MRI-based surveillance can detect many clinically occult LRs, although the studies are small, occasionally yielded conflicting results, and are often of poor quality. A survival benefit could be associated with imaging use, but further research is needed to evaluate the causality of any observed survival differences. CLINICAL IMPACT. MRI-based surveillance after surgical treatment of musculoskeletal STS is useful to detect clinically occult LRs and could improve patient outcomes.
Costs of Tuberculosis at 3 Treatment Centers, Canada, 2010-2016.
We estimated costs of managing different forms of tuberculosis (TB) across Canada by conducting a retrospective chart review and cost assessment of patients treated for TB infection, drug-susceptible TB (DS TB), isoniazid-resistant TB, or multidrug-resistant TB (MDR TB) at 3 treatment centers. We included 90 patients each with TB infection and DS TB, 71 with isoniazid-resistant TB, and 62 with MDR TB. Median per-patient costs for TB infection (in 2020 Canadian dollars) were $804 (interquartile range [IQR] $587-$1,205), for DS TB $12,148 (IQR $4,388-$24,842), for isoniazid-resistant TB $19,319 (IQR $7,117-$41,318), and for MDR TB $119,014 (IQR $80,642-$164,015). Compared with costs for managing DS TB, costs were 11.1 (95% CI 9.1-14.3) times lower for TB infection, 1.7 (95% CI 1.3-2.1) times higher for isoniazid-resistant TB, and 8.1 (95% CI 6.1-10.6) times higher for MDR TB. Broadened TB infection treatment could avert high costs associated with managing TB disease.
Systematic on-site testing for SARS-CoV-2 infection among asymptomatic essential workers in Montréal, Canada: a prospective observational and cost-assessment study.
BackgroundEssential workers are at increased risk for SARS-CoV-2 infection. We aimed to estimate the yield, acceptability and cost of systematic workplace-based testing of asymptomatic essential workers for SARS-CoV-2 infection.MethodsFrom Jan. 27 to Mar. 12, 2021, we prospectively recruited non-health care essential businesses in Montréal, Canada, through email or telephone contact. Two trained mobile teams, each composed of 2 non-health care professionals, visited businesses. Consenting asymptomatic employees provided saline gargle samples under supervision. Samples were analyzed by means of reverse transcription polymerase chain reaction (RT-PCR). At businesses with outbreaks (≥ 2 participants with a positive result), we retested all participants with a negative result on initial testing. Our primary outcomes were yield (proportion of test results that were positive), acceptability (proportion of participants estimated to be present at the business who agreed to participate) and costs (including training, sample collection and analysis, and communicating results). Our secondary outcome was identification of factors associated with a positive test result on multivariable logistic regression.ResultsOf the 366 businesses contacted, 69 (18.8%) agreed to participate. Nineteen businesses (28%) were manufacturers or suppliers, 12 (17%) were in auto sales or repair, and 11 (16%) were in childcare; the corresponding number of employees was 1225, 242 and 113. The median number of participants per business was 13 (interquartile range [IQR] 8-22). Of an estimated 2348 employees on site, 2128 (90.6%) participated (808 [38.0%] female, median age 48 [IQR 37-57] yr). Of the 2626 tests performed, 53 (2.0%) gave a positive result. Self-reported nonwhite ethnicity (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI] 1.4-9.9) and a negative SARS-CoV-2 test result before the study (adjusted OR 0.4, 95% CI 0.2-0.8) were associated with a positive test result. Five businesses were experiencing an outbreak; at these businesses, 40/917 participants (4.4%) had a positive result on the initial test. We repeated testing for employees with initially negative results at 3 of these businesses over 2-3 weeks: 8/350 participants (2.3%) had a positive result on the second test, and none had a positive result on the third and fourth tests; no employer reported new positive results after our final visit (up to Mar. 26, 2021). At the remaining 64 businesses, 1211 participants were tested once, of whom 5 (0.4%) had a positive result. The per-person RT-PCR cost was $34, and all other costs, $8.67.InterpretationOn-site saline gargle sampling of essential workers for SARS-CoV-2 testing was acceptable and of modest cost, and appears most useful in the context of outbreaks. This sampling strategy should be evaluated further as a component of efforts to prevent SARS-CoV-2 transmission. PREPRINT: medRxiv - doi:10.1101/2021.05.12.21256956.
Active screening for tuberculosis in high-incidence Inuit communities in Canada: a cost-effectiveness analysis.
BackgroundActive screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik.MethodsWe incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs.ResultsGiven a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening.InterpretationActive screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.
Economic and modeling evidence for tuberculosis preventive therapy among people living with HIV: A systematic review and meta-analysis.
BackgroundHuman immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes.Methods and findingsWe searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications.ConclusionsThe body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.
Social and behavioral risk reduction strategies for tuberculosis prevention in Canadian Inuit communities: a cost-effectiveness analysis.
BackgroundTuberculosis (TB) is an important public health problem in Inuit communities across Canada, with an annual incidence rate in 2017 that was nearly 300 times higher than in Canadian-born non-Indigenous individuals. Social and behavioral factors that are prevalent in the North, such as commercial tobacco use, excessive alcohol use, food insecurity and overcrowded housing put individuals at higher risk for TB morbidity and mortality. We examined the potential impact of mitigation strategies for these risk factors, in reducing TB burden in this setting.MethodsWe created a transmission model to simulate the epidemiology of TB in Nunavut, Canada. We then used a decision analysis model to assess the potential impact of several evidence-based strategies targeting tobacco use, excessive alcohol use, food insecurity and overcrowded housing. We predicted TB incidence, TB-related deaths, quality adjusted life years (QALYs), and associated costs and cost-effectiveness over 20 years. All costs were expressed in 2018 Canadian dollars.ResultsCompared to a status quo scenario with no new interventions for these risk factors, the reduction strategy for tobacco use was most effective and cost-effective, reducing TB incidence by 5.5% (95% uncertainty range: 2.7-11%) over 20 years, with an estimated cost of $95,835 per TB case prevented and $49,671 per QALY gained. The addition of the food insecurity reduction strategy reduced incidence by a further 2% (0.5-3%) compared to the tobacco cessation strategy alone, but at significant cost.ConclusionsStrategies that aim to reduce commercial tobacco use and improve food security will likely lead to modest reductions in TB morbidity and mortality. Although important for the communities, strategies that address excess alcohol use and overcrowding will likely have a more limited impact on TB-related outcomes at current scale, and are associated with much higher cost. Their benefits will be more substantial with scale up, which will also likely have important downstream impacts such as improved mental health, educational attainment and food security.