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We describe the case of a patient who presented with a right-sided glomus jugulare tumor and bilateral glomus vagale tumors. These proved to be nonmalignant paragangliomas on histopathological analysis. Genetic analysis revealed a germline heterozygous missense mutation (Pro81Leu) in the succinate dehydrogenase subunit D (SDHD) gene. We discuss the clinical presentations of the familial paraganglioma syndrome type 1, which is caused by mutations in SDHD, and the implications for the clinical diagnosis and care of such patients.

Rapid growth of the embryonic heart occurs by addition of progenitor cells of the second heart field to the poles of the elongating heart tube. Failure or perturbation of this process leads to congenital heart defects. In order to provide further insight into second heart field development we characterized the insertion site of a transgene expressed in the second heart field and outflow tract as the result of an integration site position effect.Here we show that the integration site of the A17-Myf5-nlacZ-T55 transgene lies upstream of Hes1, encoding a basic helix-loop-helix containing transcriptional repressor required for the maintenance of diverse progenitor cell populations during embryonic development. Transgene expression in a subset of Hes1 expression sites, including the CNS, pharyngeal epithelia, pericardium, limb bud and lung endoderm suggests that Hes1 is the endogenous target of regulatory elements trapped by the transgene. Hes1 is expressed in pharyngeal endoderm and mesoderm including the second heart field. Analysis of Hes1 mutant hearts at embryonic day 15.5 reveals outflow tract alignment defects including ventricular septal defects and overriding aorta. At earlier developmental stages, Hes1 mutant embryos display defects in second heart field proliferation, a reduction in cardiac neural crest cells and failure to completely extend the outflow tract.Hes1 is expressed in cardiac progenitor cells in the early embryo and is required for development of the arterial pole of the heart.

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.)

Objectives: This study examined whether poverty (neighborhood and household) was associated with future health or life satisfaction outcomes and whether the association operated through social support (adult support at home, adult support at school, peer belonging), or differed by the immigration background (nonimmigrant family or immigrant family) of the family., Methods: This study utilized a retrospective, longitudinal, population-based cohort that included self-reported survey data from the Middle Years Development Instrument (MDI) completed by children at age 9 and age 12, linked to administrative records. Participants included 5906 children in British Columbia, Canada. Neighborhood and household poverty were observed at age 8. Social support from adults and peers was self-reported at age 9. Outcomes (overall health; life satisfaction) were self-reported at age 12. Adjusted multi-level multiple linear regression analyses and parallel mediation analyses were utilized. The interaction between poverty exposure and immigration background was also examined., Results: Exposure to either poverty type was associated with lower levels of life satisfaction and overall health at age 12, though household poverty appeared to be associated with lower outcomes in comparison to neighborhood poverty. The indirect effects of poverty on outcomes appeared to operate primarily through adult support at home and peer belonging. Children in immigrant families had a larger negative association between neighborhood poverty and life satisfaction., Conclusions: Household poverty had a larger negative association to outcomes in comparison to neighborhood poverty. The association of poverty to outcomes differed by immigration background and operated partially through adult support at home and peer belonging., (© 2024 The Author(s). Journal of Adolescence published by John Wiley & Sons Ltd on behalf of Foundation for Professionals in Services to Adolescents.)

Objective: Identifying the effects of comorbidity on healthcare utilization is critical for understanding the benefits of improved comorbidity management. Asthma is a common respiratory condition, associated with gastrointestinal, metabolic, psychiatric, and other respiratory conditions. Adults with asthma represent a key population in understanding comorbidity and its consequences. The objective was to explore the relationship between comorbidity and overnight hospitalizations in U.S. adults with asthma., Study Design and Methods: A cross-sectional sample of 3,887 subjects aged 20-79 was aggregated from seven cycles (2005-2018) of the National Health and Nutrition Examination Survey (NHANES). The survey design was created using the full seven cycles, then a subpopulation was used for the analysis. Design-based modified Poisson regression with robust standard errors compared the prevalence of overnight hospitalizations in subjects with and without comorbidities. Comorbidity was defined as the presence of one or more additional chronic conditions., Results: Over half (61.6%) of patients with asthma reported having comorbidities. The overnight hospitalization prevalence was higher in those with comorbidities (21.6%) than those without (7.4%). The adjusted prevalence ratio of overnight hospitalizations in those with comorbidities vs. those without was 2.02 (95% CI: 1.54-2.66). Conclusions from sensitivity analyses remained the same., Conclusions: Comorbidity in U.S. adult asthma patients is associated with increased overnight hospitalizations. Study results concur with examinations of other healthcare utilization outcomes, revealing how comorbidity influences healthcare utilization patterns in patients with asthma. The reduction of overnight hospitalizations should be a targeted goal when developing and evaluating interventions to manage comorbidities in patients with asthma.

Within epidemiological research, estimating treatment effects from observational data presents notable challenges. Targeted Maximum Likelihood Estimation (TMLE) emerges as a robust method, addressing these challenges by accurately modeling treatment effects. This approach uniquely combines the precision of correctly specified models with the versatility of data-adaptive, flexible machine learning algorithms. Despite its effectiveness, TMLE's integration of complex algorithms can introduce bias and under-coverage. This issue is addressed through the Double Cross-fit TMLE (DC-TMLE) approach, enhancing accuracy and reducing biases inherent in observational studies. However, DC-TMLE's potential remains underexplored in epidemiological research, primarily due to the lack of comprehensive methodological guidance and the complexity of its computational implementation. Recognizing this gap, our paper contributes a detailed, reproducible guide for implementing DC-TMLE in R, aimed specifically at epidemiological applications. We demonstrate the utility of this method using an openly available clinical dataset, underscoring its relevance and adaptability for robust epidemiological analysis. This guide aims to facilitate broader adoption of DC-TMLE in epidemiological studies, promoting more accurate and reliable treatment effect estimations in observational research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Importance: Previous studies on the comparative effectiveness between buprenorphine and methadone provided limited evidence on differences in treatment effects across key subgroups and were drawn from populations who use primarily heroin or prescription opioids, although fentanyl use is increasing across North America., Objective: To assess the risk of treatment discontinuation and mortality among individuals receiving buprenorphine/naloxone vs methadone for the treatment of opioid use disorder., Design, Setting, and Participants: Population-based retrospective cohort study using linked health administrative databases in British Columbia, Canada. The study included treatment recipients between January 1, 2010, and March 17, 2020, who were 18 years or older and not incarcerated, pregnant, or receiving palliative cancer care at initiation., Exposures: Receipt of buprenorphine/naloxone or methadone among incident (first-time) users and prevalent new users (including first and subsequent treatment attempts)., Main Outcomes and Measures: Hazard ratios (HRs) with 95% compatibility (confidence) intervals were estimated for treatment discontinuation (lasting ≥5 days for methadone and ≥6 days for buprenorphine/naloxone) and all-cause mortality within 24 months using discrete-time survival models for comparisons of medications as assigned at initiation regardless of treatment adherence ("initiator") and received according to dosing guidelines (approximating per-protocol analysis)., Results: A total of 30 891 incident users (39% receiving buprenorphine/naloxone; 66% male; median age, 33 [25th-75th, 26-43] years) were included in the initiator analysis and 25 614 in the per-protocol analysis. Incident users of buprenorphine/naloxone had a higher risk of treatment discontinuation compared with methadone in initiator analyses (88.8% vs 81.5% discontinued at 24 months; adjusted HR, 1.58 [95% CI, 1.53-1.63]), with limited change in estimates when evaluated at optimal dose in per-protocol analysis (42.1% vs 30.7%; adjusted HR, 1.67 [95% CI, 1.58-1.76]). Per-protocol analyses of mortality while receiving treatment exhibited ambiguous results among incident users (0.08% vs 0.13% mortality at 24 months; adjusted HR, 0.57 [95% CI, 0.24-1.35]) and among prevalent users (0.08% vs 0.09%; adjusted HR, 0.97 [95% CI, 0.54-1.73]). Results were consistent after the introduction of fentanyl and across patient subgroups and sensitivity analyses., Conclusions and Relevance: Receipt of methadone was associated with a lower risk of treatment discontinuation compared with buprenorphine/naloxone. The risk of mortality while receiving treatment was similar for buprenorphine/naloxone and methadone, although the CI estimate for the hazard ratio was wide.

Introduction: Multiple sclerosis (MS) has a high comorbidity burden. Despite known associations with adverse outcomes, a comprehensive evaluation of the specific associations between individual comorbidities and disability, treatment initiation, and mortality remains underexplored. This study aimed to review and summarize existing evidence on the association between comorbidities and these three MS outcomes., Methods: A rapid review spanning the period from January 2002 to October 2023 was conducted following the Cochrane Rapid Review Methods Group recommendations. MEDLINE, Embase, and the grey literature were searched to identify studies examining the effects of comorbidities on disability, treatment initiation, and mortality among individuals with MS. Data extraction and risk of bias assessments were systematically performed, with the Newcastle-Ottawa scale and A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) criteria for observational studies and systematic reviews respectively., Results: The review included 100 primary studies, encompassing 88 different comorbidities. Most study populations were between 60-80% female, with an average age of 30-45 years at study start. The majority of included studies were conducted in Europe, North America, and Asia (specifically the Middle East). Over half (66%) of specific comorbidity-outcome relationships were examined within a single study only, and just two studies examined treatment initiation as an outcome. Methods used to assess comorbidities and outcomes varied widely and included self-report measures, medical records and diagnostic codes, and standardized clinical assessments. Depression was consistently associated with greater disability (adjusted hazard ratio (aHR): 1.50-3.59) and mortality (aHR: 1.62-3.55). Epilepsy was similarly associated with increased disability (aOR: 1.13-1.77) and increased mortality (aHR: 2.23-3.85). Diabetes was generally associated with increased mortality (aHR: 1.39-1.47), but results for disability were inconsistent. Most other conditions were examined in one or two studies only or findings varied across studies, unable to collectively indicate a clear association. Although the anxiety-disability relationship was assessed by 24 studies, the findings varied in terms of the presence, direction, and strength of a possible association, requiring nuanced interpretation., Conclusions: This study identifies relationships between various comorbidities and three outcomes in MS, providing a foundation for future research and clinical guidelines. People with psychiatric, metabolic, and neurological conditions may be at a higher risk of MS disease progression and may therefore benefit from the targeted treatment of their comorbidities. Overall, comorbidities have varying associations with MS outcomes and individual associations require further exploration. However, there is evidence that some comorbidities indicate worse disability and higher mortality risk, and present barriers to initiating MS treatment, making the prevention and management of comorbidities an integral piece of MS patient care., Protocol: The protocol for this rapid review was registered on PROSPERO (ID: CRD42023475565) and published on Protocol Exchange (https://doi.org/10.21203/rs.3.pex-2438/v1)., Competing Interests: Declaration of competing interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HT 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, MS 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, HT has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences or attend meetings (as a member of the International Advisory Committee on Clinical Trials in Multiple Sclerosis) from the Consortium of MS Centres (2023), the Canadian Neurological Sciences Federation (2023), National MS Society (2022, 2023, 2024), ECTRIMS/ ACTRIMS (2017–2024), 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. RAM receives research funding from: CIHR, MS Canada, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society, Pfizer Foundation and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis. LML receives research funding from CIHR, the Arthritis Society, and the Canadian Agency for Drugs and Technology in Health. She holds a Canada Research Chair. KAM receives research funding from StratNeuro and has received speaker honoraria from Biogen Inc and Sanofi. MEK is supported by the Michael Smith Foundation for Health Research Scholar award. Over the past 3 years, MEK has received consulting fees from Biogen Inc. for consulting unrelated to this current work. HAF, MC, YF, and FZ have no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Delays in diagnostic and therapeutic processes are a potentially preventable cause of morbidity and mortality. Process improvement depends on accurate knowledge about as-is processes, historically collected from front-line workers and summarized in flowcharts. Such flowcharts can now be generated by process discovery algorithms supplied with chronological records from real-world cases. However, these algorithms may generate incomprehensible flowcharts when applied to complex unstructured processes, which are common in healthcare. The aim of this study is to evaluate methods for analysing data from real-world cases to determine causes of delay in complex healthcare processes., Methods: Physician insurance claims and hospital discharge data were obtained for patients undergoing carotid endarterectomy at a single tertiary hospital between 2008 and 2014. All patients were recently symptomatic with vision loss. A chronological record of physician visits and diagnostic tests (activities) was generated for each patient using claims data. Algorithmic process discovery was attempted using the Heuristic Miner. The effect of activity selection on treatment delay was investigated from two perspectives: activity-specific effects were measured using linear regression, and patterns of activity co-occurrence were identified using K means clustering., Results: Ninety patients were included, with a median symptom-to-surgery treatment time of 34 days. Every patient had a unique sequence of activities. The flowchart generated by the Heuristic Miner algorithm was uninterpretable. Linear regression models of waiting time revealed beneficial effects of emergency and neurology visits, and detrimental effects of carotid ultrasound and post-imaging follow-up visits to family physicians and ophthalmologists. K-means clustering identified two co-occurrence patterns: emergency visits, neurology visits and CT angiography were more common in a cluster of rapidly treated patients (median symptom to surgery time of 18 days), whereas family physician visits, carotid ultrasound imaging and post-imaging follow-up visits to eye specialists were more common in a cluster of patients with treatment delay (median time of 57 days)., Conclusions: Routinely collected data provided a comprehensive account of events in the symptom-to-surgery process for carotid endarterectomy. Linear regression and K-means clustering can be used to analyze real-world data to understand causes of delay in complex healthcare processes., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the University of British Columbia Research Ethics Board (H18-02167), which waived the requirement for informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In this article, we report, to the best of our knowledge, for the first time, phase change material (PCM)-based reconfigurable metasurfaces for tailoring different degrees of freedom (DoF) of the quantum emitter (QE) emission, namely polarization and directionality, two key controlling factors in applications such as quantum computing, communication, and chiral optics. We have used a hybrid plasmon-QE coupled bullseye grating system utilizing the unexplored concept of composite nano-antennas in quantum photonics as the basic building block of the structures. Carefully engineered azimuthal width profile of the Sb 2 S 3 /AlGaAs composite ridge and selectively controlled transition of PCM (Sb 2 S 3 ) states provide dynamic control over the amplitude and phase of the scattered radiation. Based on this methodology, we have designed five different metasurfaces for on-demand switching of target DoFs of QE emission, ensuring high collection efficiency due to the near-field coupling scheme. The first two metasurfaces switch the majority of the outgoing radiation from radially polarized to circularly polarized, whereas the next two switch the direction of circularly polarized outgoing radiation by a maximum of 9.23° while maintaining the spin state (or polarization chirality) in the simulation environment. The third metasurface category is capable of on-demand generation and separation of opposite spin states of outgoing radiation by 11.48° utilizing the selectively controlled phase transition of Sb 2 S 3 . Such reconfigurable multi-dimensional manipulation of QE radiation has not been investigated previously. This work proves the vast potential of active metasurfaces to modify the DoFs of QE emission, paving the way for high-dimensional quantum sources for high-speed quantum communication, higher dimensional quantum processing, and switchable chiral optics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: Propensity score matching is vital in epidemiological studies using observational data, yet its estimates relies on correct model-specification. This study assesses supervised deep learning models and unsupervised autoencoders for propensity score estimation, comparing them with traditional methods for bias and variance accuracy in treatment effect estimations., Methods: Utilizing a plasmode simulation based on the Right Heart Catheterization dataset, under a variety of settings, we evaluated (1) a supervised deep learning architecture and (2) an unsupervised autoencoder, alongside two traditional methods: logistic regression and a spline-based method in estimating propensity scores for matching. Performance metrics included bias, standard errors, and coverage probability. The analysis was also extended to real-world data, with estimates compared to those obtained via a double robust approach., Results: The analysis revealed that supervised deep learning models outperformed unsupervised autoencoders in variance estimation while maintaining comparable levels of bias. These results were supported by analyses of real-world data, where the supervised model's estimates closely matched those derived from conventional methods. Additionally, deep learning models performed well compared to traditional methods in settings where exposure was rare., Conclusion: Supervised deep learning models hold promise in refining propensity score estimations in epidemiological research, offering nuanced confounder adjustment, especially in complex datasets. We endorse integrating supervised deep learning into epidemiological research and share reproducible codes for widespread use and methodological transparency., (© 2024. The Author(s).)

Purpose: Household air pollution is one of the leading causes of death and disease globally. Emerging evidence of elevated risk of neonatal death has been reported in Africa and South Asia. However, evidence on the extent of the problem in Latin America is limited despite the persistent use of highly polluting cooking fuels. We assessed whether the use of high-polluting household cooking fuels increases the risk of neonatal death compared to low-polluting fuels in Colombia., Methods: We used cross-sectional data from the 2005-2015 Colombian Demographic Health Survey and performed a survey-featured multivariate logistic regression. We selected adjustment covariates based on a causal diagram, addressed missing data through multiple imputation, and conducted several sensitivity analysis, such as propensity score matching., Result: We found evidence suggesting an increased risk of neonatal death in households using high-polluting fuels (OR: 1.48; 95% CI: 0.91, 2.39). The sensitivity analyses were consistent with the main analysis., Conclusion: We observed increased odds of neonatal death associated with using high-polluting household cooking fuels compared to low-polluting fuels, although this association was not statistically significant. This study contributes evidence to a region where the issue is not yet a priority and should be included in national-level discussions and interventions that impact cooking fuel use patterns., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: In many jurisdictions, policies restrict access to Opioid Agonist Treatment (OAT) in correctional facilities. Receipt of OAT during incarceration is associated with reduced risk of fatal overdose after release but little is known about the effect on nonfatal overdose. This study aimed to examine the association between OAT use during incarceration and nonfatal overdose in the 30 days following release., Methods and Findings: Using linked administrative healthcare and corrections data for a random sample of 20% of residents of British Columbia, Canada we examined releases from provincial correctional facilities between January 1, 2015 -December 1, 2018, among adults (aged 18 or older at the time of release) with Opioid Use Disorder. We fit Andersen-Gill models to examine the association between receipt of OAT in custody and the hazard of nonfatal following release. We conducted secondary analyses to examine the association among people continuing treatment initiated prior to their arrest and people who initiated a new episode of OAT in custody separately. We also conducted sex-based subgroup analyses. In this study there were 4,738 releases of 1,535 people with Opioid Use Disorder. In adjusted analysis, receipt of OAT in custody was associated with a reduced hazard of nonfatal overdose (aHR 0.55, 95% CI 0.41, 0.74). This was found for prescriptions continued from community (aHR 0.49, 95%CI 0.36, 0.67) and for episodes of OAT initiated in custody (aHR 0.58, 95%CI 0.41, 0.82). The effect was greater among women than men., Conclusions: OAT receipt during incarceration is associated with a reduced hazard of nonfatal overdose after release. Policies to expand access to OAT in correctional facilities, including initiating treatment, may help reduce harms related to nonfatal overdose in the weeks following release. Differences in the effect seen among women and men indicate a need for gender-responsive policies and programming., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 McLeod et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To address the growing demand for sustainable agriculture practices, new technologies to boost crop productivity and soil health must be developed. In this research, we propose designing and building an agricultural rover capable of autonomous vegetable harvesting and soil analysis utilizing cutting-edge deep learning algorithms (YOLOv5). The precision and recall score of the model was 0.8518% and 0.7624% respectively. The rover uses robotics, computer vision, and soil sensing technology to perform accurate and efficient agricultural tasks. We go over the rover's hardware and software, as well as the soil analysis system and the tomato ripeness detection system using deep learning models. Field experiments indicate that this agricultural rover is effective and promising for improving crop management and soil monitoring in modern agriculture, hence achieving the UN's SDG 2 Zero Hunger goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Das et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Students who identify with a chronic physical condition are a growing population and their conditions may be associated with poor mental well-being., Aim: To compare suicidal ideation prevalence between Canadian school-attending young adults with and without a chronic physical condition. We hypothesized that students living with a chronic condition have a higher likelihood of experiencing suicidal ideation., Methods: A cross-sectional study was conducted using a nationally representative sample of 2297 Canadian school-attending young adults (ages 15-29 years) from the 2012-13 Canadian Community Health Survey-Mental Health (CCHS-MH). Survey-weighted logistic regression and sensitivity analyses were performed to estimate the likelihood of experiencing suicidal ideation between students with and without a chronic physical condition., Results: Approximately 14.3% (n = 329) students experienced suicidal ideation at some point. Students living with a physical chronic condition demonstrated 1.65 (95% CI: 1.14, 2.39) times higher odds of experiencing suicidal ideation, compared to students not living with a chronic physical condition., Conclusions: Suicide prevention and health promotion are important considerations for campus health providers and administrators when planning services and accommodations for students living with chronic physical conditions.

This study investigated the association between previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of symptoms associated with post-COVID conditions among fully vaccinated paramedics in Canada. We included vaccinated paramedics who provided blood sample and questionnaire data on the same date during the study period. We examined the presence of symptoms associated with post-COVID conditions and depression severity against prior SARS-CoV-2 infection categories. Compared to the "no previous SARS-CoV-2 infection" group, there was no detected association between known prior SARS-CoV-2 infection (odds ratio [OR], 1.42 [95% confidence interval {CI}, 0.96-2.09]), nor unknown prior SARS-CoV-2 infection (OR, 0.54 [95% CI, 0.29-1.00]), and the presence of symptoms associated with post-COVID conditions., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Instrumental variable (IV) analysis provides an alternative set of identification assumptions in the presence of uncontrolled confounding when attempting to estimate causal effects. Our objective was to evaluate the suitability of measures of prescriber preference and calendar time as potential IVs to evaluate the comparative effectiveness of buprenorphine/naloxone versus methadone for treatment of opioid use disorder (OUD)., Methods: Using linked population-level health administrative data, we constructed five IVs: prescribing preference at the individual, facility, and region levels (continuous and categorical variables), calendar time, and a binary prescriber's preference IV in analyzing the treatment assignment-treatment discontinuation association using both incident-user and prevalent-new-user designs. Using published guidelines, we assessed and compared each IV according to the four assumptions for IVs, employing both empirical assessment and content expertise. We evaluated the robustness of results using sensitivity analyses., Results: The study sample included 35,904 incident users (43.3% on buprenorphine/naloxone) initiated on opioid agonist treatment by 1585 prescribers during the study period. While all candidate IVs were strong (A1) according to conventional criteria, by expert opinion, we found no evidence against assumptions of exclusion (A2), independence (A3), monotonicity (A4a), and homogeneity (A4b) for prescribing preference-based IV. Some criteria were violated for the calendar time-based IV. We determined that preference in provider-level prescribing, measured on a continuous scale, was the most suitable IV for comparative effectiveness of buprenorphine/naloxone and methadone for the treatment of OUD., Conclusions: Our results suggest that prescriber's preference measures are suitable IVs in comparative effectiveness studies of treatment for OUD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

In this article, we report, as per our knowledge, for the first time, a thin film single junction solar cell with a metasurface absorber layer directly incorporated. We have used an interconnected dual inverted split ring resonator pattern in the InAsP absorber layer. The structure eliminated patterns of conventional metals, such as silver, aluminum, and gold, from the active layer, a common drawback in conventional solar absorbers, hindering their direct integration into solar cells. Optical simulation results show a peak ideal short circuit current density of 76.23mA/cm 2 for the meta-absorber structure under solar illumination. This current is the highest among previously reported absorbers based on Group IV materials and III-V compounds, overcoming the low solar absorption of such metasurfaces. The final proposed solar cell structure combines this meta-absorber layer with traditional efficiency enhancement methods namely anti-reflecting coating, textured back reflector, and transparent top electrode. This novel single junction structure shows a solar absorption efficiency of 97.86% and a power conversion efficiency of 30.87%, the highest for III-V solar cells. Our device proves the ability of metasurface absorber layers to produce high-efficiency solar cells and is expected to pave the way for integrating novel meta-devices into state-of-the-art photovoltaic devices, aiding the global transition towards clean energy sources.

Recent research has highlighted the Omicron variant's capacity to evade immune protection conferred by wild-type (WT) mRNA vaccines. Despite this observation, the potential involvement of antigenic sin phenomena remains unclear. Our hypothesis posited that a greater number of prior WT vaccine doses might lead to reduced anti-Omicron neutralization Abs following Omicron infection. To investigate this, we analyzed blood samples from human participants in the COVID-19 Occupational Risk, Seroprevalence, and Immunity among Paramedics (CORSIP) study who had received at least one WT mRNA vaccine before contracting Omicron. The exposure variable was the number of WT mRNA vaccines administered, and the outcome was the angiotensin-converting enzyme 2 (ACE-2) percent inhibition specific to the BA.4/BA.5 Omicron Ag. Contrary to expectations, our findings revealed that more WT-based vaccines were associated with an enhanced Omicron-specific immune response., (Copyright © 2024 The Authors.)

Objectives: Occupational noise exposure may be associated with an increased risk of cardiovascular disease (CVD). Yet the findings are inconclusive. This study aimed to examine the association between self-reported occupational noise exposure and CVD (using a broad composite case definition and by each condition) and identify how these associations vary with the intensity and duration of noise exposure, and combinations thereof., Methods: This cross-sectional study included a nationally representative sample (n = 6,266) from the National Health and Nutrition Examination Survey (2015 to 2020), aged 20 and greater, in the United States. Survey-weighted logistic regression models were constructed from multiple imputed datasets., Results: Relative to the unexposed, the adjusted odds ratio (95% confidence interval) of composite CVD was 1.33 (1.05 to 1.67) among the noise-exposed population, and ranged from 1.23 to 1.56 when examining CVD conditions separately. The odds ratios of composite CVD were 1.43 (1.06 to 1.93), 1.43 (1.04 to 1.95), and 1.51 (1.03 to 2.21) among those who had noise exposure with very loud intensity of any duration, with duration ≥10 years at any intensity, and with a combination of very loud noise ≥10 years, respectively, compared to those unexposed., Conclusions: Increased risk of CVD is associated with occupational noise exposure, particularly at higher intensities and longer durations. Policies and interventions for noise mitigation at workplaces are warranted, targeting individuals with chronic exposure to high-level noise., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: In Italy, surgeons continue to drain the abdominal cavity in more than 50 per cent of patients after colorectal resection. The aim of this study was to evaluate the impact of abdominal drain placement on early adverse events in patients undergoing elective colorectal surgery., Methods: A database was retrospectively analysed through a 1:1 propensity score-matching model including 21 covariates. The primary endpoint was the postoperative duration of stay, and the secondary endpoints were surgical site infections, infectious morbidity rate defined as surgical site infections plus pulmonary infections plus urinary infections, anastomotic leakage, overall morbidity rate, major morbidity rate, reoperation and mortality rates. The results of multiple logistic regression analyses were presented as odds ratios (OR) and 95 per cent c.i., Results: A total of 6157 patients were analysed to produce two well-balanced groups of 1802 patients: group (A), no abdominal drain(s) and group (B), abdominal drain(s). Group A versus group B showed a significantly lower risk of postoperative duration of stay >6 days (OR 0.60; 95 per cent c.i. 0.51-0.70; P < 0.001). A mean postoperative duration of stay difference of 0.86 days was detected between groups. No difference was recorded between the two groups for all the other endpoints., Conclusion: This study confirms that placement of abdominal drain(s) after elective colorectal surgery is associated with a non-clinically significant longer (0.86 days) postoperative duration of stay but has no impact on any other secondary outcomes, confirming that abdominal drains should not be used routinely in colorectal surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: HCV infection is associated with mortality due to extrahepatic manifestations (EHM). Sustained virologic response (SVR) following direct-acting antiviral (DAA) therapy has been linked to decreased all-cause and liver-related mortality. However, evidence regarding the impact of DAA on EHM-related deaths is lacking. This study aimed to assess the impact of DAA and SVR on EHM-related mortality., Methods: The British Columbia Hepatitis Testers Cohort comprises ∼1.7 million people tested for HCV between 1990 and 2015 and is linked with administrative health data. Among individuals diagnosed with HCV by 12/31/2020, those who received at least one DAA treatment were matched to those who never received treatment by the year of their first HCV RNA positive date. We compared three groups: treated & SVR, treated & no-SVR, and untreated; and generated EHM mortality rates and incidence curves. To account for differences in baseline characteristics, we used inverse probability of treatment weights (IPTW). IPTW-weighted multivariable cause-specific Cox regression models were adjusted for competing risk and confounders., Findings: Study population included 12,815 treated (12,287 SVR, 528 no-SVR) and 12,815 untreated individuals (median follow-up 3.4 years, IQR 2.9). The untreated group had the highest EHM mortality rate (30.9 per 1000 person-years [PY], 95% CI 29.2-32.8), followed by the treated & no-SVR group (21.2 per 1000 PY, 95% CI 14.9-30.1), while the treated & SVR group had the lowest EHM mortality rate (7.9 per 1000 PY, 95% CI 7.1-8.7). In the multivariable model, EHM mortality in the treated & SVR group was significantly decreased (adjusted cause-specific hazard ratio [acsHR] 0.20, 95% CI 0.18-0.23). The treated & SVR group had significant reductions in mortality related to each of the EHMs (78-84%)., Interpretation: Treatment of HCV with DAA was associated with significant reductions in EHM-related mortality. These findings emphasize the critical importance of timely diagnosis and treatment of HCV to prevent deaths associated with EHM, and have important implications for clinical practice and public health., Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-348216, PJT-156066, and PHE-337680]. DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and Doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC)., Competing Interests: MK has received grant/research support from Roche, Merck, Siemens, Boeringer Ingelheim and Hologic. SRB has consulted for Cepheid, Gilead, and Abbvie, but no personal payments accepted, and has received investigator-initiated grants from Gilead and Abbvie through her institution. NZJ participated in advisory boards and has spoken for AbbVie and Gilead, not related to current work. DJ, SW, MEK, ARM, JDM, HAVG, DL, PA, MB and AY have no conflicts of interest to declare., (© 2023 The Author(s).)

Background: We examined the 11 month longitudinal antibody decay among two-dose mRNA vaccinees, and identified factors associated with faster decay., Methods: The study included samples from the COVID-19 Occupational Risk, Seroprevalence and Immunity among Paramedics (CORSIP) longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11 months post-vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time., Results: This analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the twenty-first day (antibody level 9042 U ml -1 ) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter, with a half-life of 94 [95 % CI: 70, 143] days, with levels plateauing at 295 days (antibody level 1021 U ml -1 ). Older age, vaccine dosing interval <35 days, and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay., Conclusion: Antibody levels declined after the initial mRNA series with a half-life of 94 days, plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Objectives: Poverty exposes children to adverse conditions that negatively impact development. However, there is limited understanding on how different types of poverty may affect children of various immigration backgrounds differently in outcomes such as school readiness. This study examined these relationships between household and/or neighbourhood poverty, poverty timing, and immigration background with school readiness outcomes at kindergarten., Methods: This study utilized a retrospective, population-based cohort of administrative records linked with surveys completed by kindergarten teachers for 15 369 children born in British Columbia, Canada. The exposures investigated were neighbourhood poverty (residing in a neighbourhood in the lowest income-quintile) and/or household poverty (receiving a health insurance subsidy due to low household income). Experiencing both neighbourhood and household poverty simultaneously was defined as "combined" household and neighbourhood poverty. The outcome of vulnerability on school readiness domains was assessed at kindergarten (47.8% female; mean age = 6.01 years) using teacher ratings on the Early Development Instrument (EDI)., Results: Children exposed to combined poverty between age 0 and 2 had greater odds of being vulnerable in two or more domains of school readiness than children not exposed to any poverty during this period (adjusted odds ratio (aOR) = 2.07, 95% CI: [1.74; 2.47], p < 0.001). The effect of combined poverty was larger than household poverty only (aOR = 1.54, 95% CI: [1.31; 1.82], p < 0.001) or neighbourhood poverty only (aOR = 1.49, 95% CI: [1.30; 1.70], p < 0.001). Combined poverty was associated with negative outcomes regardless of timing. Both non-immigrants (aOR = 2.40, 95% CI: [1.92; 3.00], p < 0.001) and second-generation immigrants (aOR = 1.63, 95% CI: [1.22; 2.17], p < 0.001) experiencing combined poverty scored lower on school readiness., Conclusions: Children who experienced combined poverty had lower levels of school readiness at kindergarten, regardless of timing and immigration background., (© 2023 The Authors.)

Background: Recent data have demonstrated that healthcare use after treatment for respiratory tuberculosis (TB) remains elevated in the years following treatment completion. However, it remains unclear which TB survivors are high healthcare users and whether any variation exists within this population. Thus, the primary objective of this study was to identify distinct profiles of high healthcare-use TB survivors to help inform post-treatment support and care., Methods: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals who completed treatment for incident respiratory TB between 1990 and 2019. We defined high healthcare-use TB survivors as those in the top 10% of annual emergency department visits, hospital admissions, or general practitioner visits among the study population during the five-year period immediately following TB treatment completion. We then used latent class analysis to categorize the identified high healthcare-use TB survivors into subgroups., Results: Of the 1,240 people who completed treatment for respiratory TB, 258 (20.8%) people were identified as high post- TB healthcare users. Latent class analysis results in a 2-class solution. Class 1 (n = 196; 76.0%) included older individuals (median age 71.0; IQR 59.8, 79.0) with a higher probability of pre-existing hypertension and diabetes (41.3% and 33.2%, respectively). Class 2 (n = 62; 24.0%) comprised of younger individuals (median age 31.0; IQR 27.0, 41.0) with a high probability (61.3%) of immigrating to Canada within five years of their TB diagnosis and a low probability (11.3%) of moderate to high continuity of primary care., Discussion: Our findings suggest that foreign-born high healthcare-use TB survivors in a high-resource setting may be categorized into distinct profiles to help guide the development of person-centred care strategies targeting the long-term health impacts TB survivors face., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Romanowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite data suggesting elevated morbidity and mortality among people who have survived tuberculosis disease, the impact of respiratory tuberculosis on healthcare utilization in the years following diagnosis and treatment remains unclear., Methods: Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals treated for respiratory tuberculosis between 1990 and 2019. We matched each person with up to four people without a tuberculosis diagnosis from the same source cohort using propensity score matching. Then, using a controlled interrupted time series analysis, we measured outpatient physician encounters and inpatient hospital admissions in the 5 years following respiratory tuberculosis diagnosis and treatment., Results: We matched 1216 individuals treated for respiratory tuberculosis to 4864 non-tuberculosis controls. Immediately following the tuberculosis diagnostic and treatment period, the monthly rate of outpatient encounters in the tuberculosis group was 34.0% (95% confidence interval [CI]: 30.7%, 37.2%) higher than expected, and this trend was sustained for the duration of the post-tuberculosis period. The excess utilization represented an additional 12.2 (95% CI: 10.6, 14.9) outpatient encounters per person over the post-tuberculosis period, with respiratory morbidity a large contributor to the excess healthcare utilization. Results were similar for hospital admissions, with an additional 0.4 (95% CI: .3, .5) hospital admissions per person over the post-tuberculosis period., Conclusions: Respiratory tuberculosis appears to have long-term impacts on healthcare utilization beyond treatment. These findings underscore the need for screening, assessment, and treatment of post-tuberculosis sequelae, as it may provide an opportunity to improve health and reduce resource use., Competing Interests: Potential conflicts of interest. K. R. reports travel support from CIHR (paid to institution). M. R. L. reports grants or contracts from CIHR and BC Ministry of Health (paid to institution); consulting fees from Health Canada, iTAD Ltd, and Canadian Agency for Drugs and Technologies in Health (CADTH) (paid to author); payment for expert testimony from Federation of Post-secondary Educators and Durham Police Association (paid to author). M. E. K. reports grants or contracts from Michael Smith Health Research BC (as reported in funding) and Natural Sciences and Engineering Research Council of Canada (both paid to institution). V. J. C. reports travel support for conferences from BC Center for Disease Control (BCCDC); participation as an independent data safety monitoring committee (IDMC) member for ACT5; and an unpaid role as board member for the BC Lung Foundation. M. G. reports travel support from CIHR Canadian HIV Trials Network (research collaborative). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Over 20 million adults in the United States live with high impact chronic pain (HICP), or chronic pain that limits life or work activities for ≥3 months. It is critically important to differentiate people with HICP from those who sustain normal activities although experiencing chronic pain. Therefore, we aim to help clinicians and researchers identify those with HICP by: 1) developing models that identify factors associated with HICP using the 2016 national health interview survey (NHIS) and 2) evaluating the performances of those models overall and by sociodemographic subgroups (sex, age, and race/ethnicity). Our analysis included 32,980 respondents. We fitted logistic regression models with LASSO (a parametric model) and random forest (a nonparametric model) for predicting HICP using the whole sample. Both models performed well. The most important factors associated with HICP were those related to underlying ill-health (arthritis and rheumatism, hospitalizations, and emergency department visits) and poor psychological well-being. These factors can be used for identifying higher-risk sub-groups for screening for HICP. We will externally validate these findings in future work. We need future studies that longitudinally predict the initiation and maintenance of HICP, then use this information to prevent HICP and direct patients to optimal treatments. PERSPECTIVE: Our study developed models to identify factors associated with high-impact chronic pain (HICP) using the 2016 National Health Interview Survey. There was homogeneity in the factors associated with HICP by gender, age, and race/ethnicity. Understanding these risk factors is crucial to support the identification of populations and individuals at highest risk for developing HICP and improve access to interventions that target these high-risk subgroups., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Gambian Ministry of Health is supportive of HIV self-testing (HIVST) and HIVST initiatives are being piloted as an additional strategy to increase HIV testing for individuals not currently reached by existing services, particularly men. This study aimed to determine awareness of HIVST among Gambian men, and whether prior awareness of HIVST is associated with recent HIV testing uptake., Methods: We used men's cross-sectional data from the 2019-2020 Gambian Demographic and Health Survey. We employed design-adjusted multivariable logistic regression to examine the association between HIVST awareness and recent HIV testing. Propensity-score weighting was conducted as sensitivity analyses., Results: Of 3,308 Gambian men included in the study, 11% (372) were aware of HIVST and 16% (450) received HIV testing in the last 12 months. In the design-adjusted multivariable analysis, men who were aware of HIVST had 1.76 times (95% confidence interval: 1.26-2.45) the odds of having an HIV test in the last 12 months, compared to those who were not aware of HIVST. Sensitivity analyses revealed similar findings., Conclusion: Awareness of HIVST may help increase the uptake of HIV testing among men in Gambia. This finding highlights HIVST awareness-raising activities to be an important intervention for nationwide HIVST program planning and implementation in Gambia., (© 2023. The Author(s).)

We investigated cardiovascular disease (CVD) risk associated with latent tuberculosis infection (LTBI) (Aim-1) and LTBI therapy (Aim-2) in British Columbia, a low-tuberculosis-incidence setting. 49,197 participants had valid LTBI test results. Cox proportional hazards model was fitted, adjusting for potential confounders. Compared with the participants who tested LTBI negative, LTBI positive was associated with an 8% higher CVD risk in complete case data (adjusted hazard ratio (HR): 1.08, 95% CI: 0.99-1.18), a statistically significant 11% higher risk when missing confounder values were imputed using multiple imputation (HR: 1.11, 95% CI: 1.02-1.20), and 10% higher risk when additional proxy variables supplementing known unmeasured confounders were incorporated in the highdimensional disease risk score technique to reduce residual confounding (HR: 1.10, 95% CI: 1.01-1.20). Also, compared with participants who tested negative, CVD risk was 27% higher among people who were LTBI positive but incomplete LTBI therapy (HR: 1.27, 95% CI: 1.04-1.55), whereas the risk was similar in people who completed LTBI therapy (HR: 1.04, 95% CI: 0.87-1.24). Findings were consistent in different sensitivity analyses. We concluded that LTBI is associated with an increased CVD risk in low-tuberculosis-incidence settings, with a higher risk associated with incomplete LTBI therapy and attenuated risk when therapy is completed.

Background: Cognitive impairment occurs in 40%-70% of persons with multiple sclerosis (MS)., Objective: To examine the effectiveness of natalizumab compared with other disease-modifying treatments (DMTs) on improving cognition as measured by the Symbol Digit Modalities Test (SDMT)., Methods: Data were collected as part of Swedish nationwide phase IV surveillance studies (2007-2020). An increase in SDMT score by ⩾10% of the difference between maximum score possible (110) and the baseline value was defined as cognitive improvement. The likelihood of improvement was compared between natalizumab-treated individuals and individuals treated with other DMTs using mixed effect logistic regression. Trend in odds of improvement was investigated using slope analyses., Results: We included 2100 persons with relapsing-remitting MS treated with natalizumab and 2622 persons treated with other DMTs. At 6 months, 45% reached improvement. The natalizumab group showed largest odds of improvement during follow-up (odds ratio: 2.3, 95% confidence interval (CI): 1.5-3.5). The odds of improvement increased by 7% (95% CI: 6-7) per month of natalizumab treatment. The equivalent estimate was 4% (95% CI: 2-5) for other monoclonal antibodies and nonsignificant for oral or platform therapies., Conclusion: Treatment with natalizumab or other monoclonal antibodies is associated with a significantly faster likelihood of cognitive improvement than platform or oral DMTs.

Objectives: Multimorbidity is the presence of two or more chronic health conditions. Tuberculosis (TB) survivors are known to have higher prevalence of multimorbidity, although prevalence estimates from high-income low-TB incidence jurisdictions are not available and potential differences in the patterns of chronic disease among TB survivors with multimorbidity are poorly understood. In this study, we aimed to (1) compare the prevalence of multimorbidity among TB survivors with matched non-TB controls in a high-income setting; (2) assess the robustness of aim 1 analyses to different modelling strategies, unmeasured confounding, and misclassification bias; and (3) among people with multimorbidity, elucidate chronic disease patterns specific to TB survivors., Methods: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015, using health administrative data. Participants were divided into two groups: people diagnosed with TB (TB survivors) and people not diagnosed with TB (non-TB controls) in British Columbia. Coarsened exact matching (CEM) balanced demographic, immigration, and socioeconomic covariates between TB survivors and matched non-TB controls. Our primary outcome was multimorbidity, defined as ≥2 chronic diseases from the Elixhauser comorbidity index., Results: In the CEM-matched sample (n=1962 TB survivors; n=1962 non-TB controls), we estimated that 21.2% of TB survivors (n=416), compared with 12% of non-TB controls (n=236), had multimorbidity. In our primary analysis, we found a double-adjusted prevalence ratio of 1.74 (95% CI: 1.49-2.05) between TB survivors and matched non-TB controls for multimorbidity. Among people with multimorbidity, differences were observed in chronic disease frequencies between TB survivors and matched controls., Conclusion: TB survivors had a 74% higher prevalence of multimorbidity compared with CEM-matched non-TB controls. TB-specific multimorbidity patterns were observed through differences in chronic disease frequencies between the matched samples. These findings suggest a need for TB-specific multimorbidity interventions in high-income settings such as Canada. We suggest TB survivorship as a framework for developing person-centred interventions for multimorbidity among TB survivors., (© 2022. The Author(s) under exclusive license to The Canadian Public Health Association.)

Objectives: To understand the relationship between informed choice and long-acting reversible contraceptive (LARC) use among women aged 15-49 years in Uganda after adjusting for potential confounding., Methods: This cross-sectional study uses data from the 2016 Uganda Standard Demographic and Health Survey. Thomas-Rao corrections to a χ 2 test were used for the bivariable analysis. A design-adjusted multivariable logistic regression was used to estimate the association between informed choice and LARC use. Propensity score matching was conducted as a sensitivity analysis., Results: In all, 3646 women were included in the analysis and 975 reported using a LARC. In the design-adjusted multivariable analysis, the odds of reporting LARC usage were 1.98 (95% confidence interval 1.61-2.43) times higher among women who reported informed choice compared with those who did not. The subsequent propensity score analysis reported similar findings., Conclusion: Providing informed choice can help to increase the number of women who use LARC in Uganda. As such, the Ugandan Ministry of Health should further expand access to family planning counseling as it could contribute to the reduction of unplanned pregnancies across Uganda with the use of LARC., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Despite Canada's universal health-care system, millions of Canadians experience unmet health-care needs (UHCN). People with mood disorders may be at higher risk of UHCN due to barriers such as stigma and gaps in health-care services., Aim: We aimed to examine the relationship between having a diagnosed mood disorder and experiencing UHCN using a recent, nationally representative survey., Methods: Using the 2014 Canadian Community Health Survey, we used multivariate logistic regression to estimate the association between mood disorder and UHCN in the past 12 months, adjusting for sociodemographic variables and health status., Results: Among 52,825 respondents, 11.8% reported UHCN. Respondents with a diagnosed mood disorder were more likely to report UHCN [adjusted odds ratio (OR) 1.61, 95% confidence interval (CI) 1.38, 1.89]. Among respondents with a regular doctor, people with mood disorders were still more likely to report UHCN (OR 1.63, 95% CI 1.38, 1.93). Sensitivity analyses using propensity score and missing data imputation approaches resulted in similar estimates., Conclusions: Adults diagnosed with a mood disorder are more likely to report UHCN in the past year, even those with a regular doctor. Our findings suggest that barriers beyond physician attachment may impact access to care for people with mood disorders.

The relationship between antibodies to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and the risk of breakthrough infections is unclear, especially during circulation of the Omicron strain. We investigated the association of anti-spike and anti-receptor binding domain antibody levels and the risk of subsequent breakthrough coronavirus disease 2019 (COVID-19). We included adult paramedics from an observational cohort study who received 2 mRNA vaccines but did not have COVID-19 before the blood collection. Higher postvaccination antibody levels to wild-type SARS-CoV-2 antigens were associated with a reduced risk of COVID-19. Further research into clinical utility of antibody levels, to inform a threshold for protection and timing of boosters, should be prioritized., (The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Emerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear., Methods: This study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples six months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as "short" (first quartile), "moderate" (second quartile), "long" (third quartile), and "longest " interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included spike and receptor-binding domain (RBD) immunoglobulin G (IgG) antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations., Results: A total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to "short interval" (≤30 days), vaccine dosing intervals of the long (39-73 days) group (β= 0.31, 95% Confidence interval (CI): 0.10-0.52) and the longest (≥74 days) group (β = 0.82. 95% CI: 0.36-1.28) were associated with increased spike total antibody concentration. Compared to the short interval, the longest interval quartile was associated with higher spike IgG antibodies, while the long and longest intervals were associated with higher RBD IgG antibody concentrations. Similarly, the longest dosing intervals increased inhibition of ACE-2 binding to viral spike protein., Conclusion: Increased mRNA vaccine dosing intervals longer than 38 days result in higher levels of anti-spike antibodies and ACE-2 inhibition when assessed six months after the first COVID-19 vaccine., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Asamoah-Boaheng et al.)

Pragmatic trials offer practical means of obtaining real-world evidence to help improve decision-making in comparative effectiveness settings. Unfortunately, incomplete adherence is a common problem in pragmatic trials. The commonly used methods in randomized control trials often cannot handle the added complexity imposed by incomplete adherence, resulting in biased estimates. Several naive methods and advanced causal inference methods (e.g., inverse probability weighting and instrumental variable-based approaches) have been used in the literature to deal with incomplete adherence. Practitioners and applied researchers are often confused about which method to consider under a given setting. This current work is aimed to review commonly used statistical methods to deal with non-adherence along with their key assumptions, advantages, and limitations, with a particular focus on pragmatic trials. We have listed the applicable settings for these methods and provided a summary of available software. All methods were applied to two hypothetical datasets to demonstrate how these methods perform in a given scenario, along with the R codes. The key considerations include the type of intervention strategy (point treatment settings, where treatment is administered only once versus sustained treatment settings, where treatment has to be continued over time) and availability of data (e.g., the extent of measured or unmeasured covariates that are associated with adherence, dependent confounding impacted by past treatment, and potential violation of assumptions). This study will guide practitioners and applied researchers to use the appropriate statistical method to address incomplete adherence in pragmatic trial settings for both the point and sustained treatment strategies., (© 2022 John Wiley & Sons Ltd.)

Most oropharyngeal and anogenital cancers are caused by human papillomavirus (HPV). Although HPV vaccines showed high efficacy against oropharyngeal and anogenital HPV infections, and cancer precursors in randomized clinical trials, there are limited data on the effectiveness of HPV vaccination against HPV-related cancers. We aimed to evaluate the association of HPV vaccination with HPV-related cancers among a nationally representative sample of United States adults, aged 20-59 years. In a cross-sectional study combining four cycles from the National Health and Nutrition Examination Survey, from 2011 through 2018, we used a survey-weighted logistic regression model, propensity score matching and multiple imputations by chained equations to explore the association of HPV vaccination with HPV-related cancers. Among 9891 participants, we did not find an association of HPV vaccination with HPV-related cancers (adjusted OR = 0.58, 95% CI 0.19; 1.75). Despite no statistically significant association between HPV vaccination and HPV-related cancers, our study findings suggest that HPV-vaccinated adults might have lower odds of developing HPV-related cancers than those who were not vaccinated. Given the importance of determining the impact of vaccination on HPV-related cancers, there is a need to conduct future research by linking cancer registry data with vaccination records, to obtain more robust results.

Messenger RNA (mRNA) recently emerged as an appealing alternative to treat and prevent diseases ranging from cancer and Alzheimer's disease to COVID-19 with significant clinical outputs. The in vitro-transcribed mRNA has been engineered to mimic the structure of natural mRNA for vaccination, cancer immunotherapy and protein replacement therapy. In past decades, significant progress has been noticed in unveiling the molecular pathways of mRNA, controlling its translatability and stability, and its evolutionary defense mechanism. However, numerous unsolved structural, biological, and technical difficulties hamper the successful implementation of systemic delivery of mRNA for safer human consumption. Advances in designing and manufacturing mRNA and selecting innovative delivery vehicles are mandatory to address the unresolved issues and achieve the full potential of mRNA drugs. Despite the substantial efforts made to improve the intracellular delivery of mRNA drugs, challenges associated with diverse applications in different routes still exist. This study examines the current progress of mRNA therapeutics and advancements in designing biomaterials and delivery strategies, the existing translational challenges of clinical tractability and the prospects of overcoming any challenges related to mRNA., (© 2022. The Pharmaceutical Society of Korea.)

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine-Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.

Background and Objectives: Little is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome., Methods: This was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event ("administrative cohort;" n = 6,863) or MS symptom onset ("clinical cohort;" n = 966) were compared to age-, sex- and geographically-matched controls ( n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30-49, ≥50 years)., Results: In the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30-49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30-49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30-49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30-49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30-49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance ( P ≥ 0.05)., Discussion: Sex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation., Competing Interests: Author FY was funded by a Fredrick Banting and Charles Best Canada Graduate Scholarship from the Canadian Institutes of Health Research (CIHR). Author JF receives research funding from: CIHR, Crohn's and Colitis Canada, Research Nova Scotia; consultation and distribution royalties from MAPI Research Trust. Over the past 4 years, Author MK has received consulting fees from Biogen (unrelated to the current project) and participated in Advisory Boards and/or Satellite Symposia of Biogen Inc. Author RM receives research funding from: CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC. She was supported by the Waugh Family Chair in Multiple Sclerosis. She was a co-investigator on studies funded partly by Biogen Idec and Roche (no funds to her, her institution). Author HT has, in the last 5 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 and the Multiple Sclerosis Scientific Research Foundation. In addition, in the last 5 years, has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences from the Consortium of MS Centres (2018), National MS Society (2016, 2018), ECTRIMS/ACTRIMS (2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022), American Academy of Neurology (2015, 2016, 2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by HT's research group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yusuf, Wijnands, Karim, Kingwell, Zhu, Evans, Fisk, Zhao, Marrie and Tremlett.)

As transporters of RNAi therapeutics in preclinical and clinical studies, the application of nanoparticles is often hindered by their susceptibility to opsonin-mediated clearance, poor biological stability, ineffectual targeting, and undesirable effects on healthy cells. Prolonging the blood circulation time while minimizing the off-target distribution and associated toxicity is indispensable for the establishment of a clinically viable delivery system for therapeutic small interfering RNAs (siRNAs). Herein, we report a scalable and straightforward approach to fabricate non-toxic and biodegradable pH-responsive strontium sulfite nanoparticles (SSNs) wrapped with a hydrophilic coating material, biotinylated PEG to lessen unforeseen biological interactions. Surface functionalization of SSNs with PEG led to the generation of small and uniformly distributed particles with a significant affinity towards siRNAs and augmented internalization into breast cancer cells. A triple quadrupole liquid chromatography-mass spectrometry (LC-MS) was deployed to identify the proteins entrapped onto the SSNs, with the help of SwissProt.Mus&#95;musculus database. The results demonstrated the reduction of opsonin proteins adsorption owing to the stealth effect of PEG. The distribution of PEGylated SSNs in mice after 4 h and 24 h of intravenous administration in breast tumour-bearing mice was found to be significantly less to the organs of the reticuloendothelial system (RES) and augmented accumulation in the tumour region. The anti-EGFR siRNA-loaded PEG-SSNs exerted a significant inhibitory effect on tumour development in the murine breast cancer model without any significant toxicity to healthy tissues. Therefore, PEGylated SSNs open up a new avenue for tumour-selective efficient delivery of siRNAs in managing breast cancer.

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.)

Small studies have shown reduced sodium-sensitivity of blood pressure in obese adolescents on a caloric deficit. We aimed to explore the association between mean daily sodium intake and prevalent hypertension among a nationally representative sample of U.S. adults on a calorie deficit. We used a design-based regression model to explore the association between sodium intake and prevalent hypertension. We also conducted sensitivity analyses using multiple imputation chained equations and propensity score matching. We also measured the effect of a binary exposure derived from the widely recommended threshold of 2.3 grams of sodium intake per day. Among 5756 individuals, we did not detect any significant association between increased sodium and the odds of hypertension (OR: 0.97; 95% CI: 0.90; 1.05). All our sensitivity analyses are consistent with our main findings. People on a calorie deficit-a component of healthy weight loss-without malnutrition saw no benefit in reduced sodium intake to lower blood pressure. These results highlight the need to explore new population-specific strategies for sodium intake reduction, including new dietary prescription approaches to improve dietary adherence and reduce the risk associated with sodium-deficient diets., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

SARS-CoV-2 anti-spike antibody concentrations and angiotensin converting enzyme-2 (ACE-2) inhibition have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. We tested the correlation of these measures among vaccinated participants, and examined subgroups based on duration since vaccination and vaccine dosing intervals. We analyzed 120 samples from two-dose mRNA vaccinees without previous COVID-19. We calculated Spearman correlation coefficients between wild-type viral neutralizing antibody titers and: anti-spike (total and IgG), anti-receptor-binding-domain (RBD), and anti-N-terminal-domain (NTD) antibodies; and ACE-2 binding by RBD. We performed three secondary analyses, dichotomizing samples by the first vaccination-to-blood collection interval, second vaccination-to-blood collection interval, and by the vaccine dosing interval (all groups divided by the median), and compared correlation coefficients (Fisher's Z test). Of 120 participants, 63 (53%) were women, 91 (76%) and 29 (24%) received BNT162b2 and mRNA-1273 vaccines, respectively. Overall, live viral neutralization was correlated with anti-spike total antibody (correlation coefficient = 0.80), anti-spike IgG (0.63), anti-RBD IgG (0.62), anti-NTD IgG (0.64), and RBD ACE2 binding (0.65). Samples with long (>158 days) first vaccination-to-blood collection and long (>71 days) second vaccination-to-blood collection intervals demonstrated higher correlation coefficients, compared with short groups. When comparing cases divided by short (≤39 days) versus long vaccine dosing intervals, only correlation with RBD-ACE-2 binding inhibition was higher in the long group. Among COVID-negative mRNA vaccinees, anti-spike antibody and ACE-2 inhibition concentrations are correlated with live viral neutralizing antibody titers. Correlation was stronger among samples collected at later durations from vaccination. IMPORTANCE Live viral neutralizing antibody titers are an accepted measure of immunity; however, testing procedures are labor-intensive. COVID-19 antibody and angiotensin converting enzyme-2 (ACE-2) levels have been used as surrogates to live viral neutralizing antibody titers; however, validity among vaccinated individuals is unclear. Using samples from 120 two-dose mRNA vaccinees without previous COVID-19, we found that live viral neutralization was correlated with COVID-19 antibody and ACE2 binding levels. When grouping samples by the time interval between vaccination and sample blood collection, samples collected over 158 days after the first vaccine and over 71 days from the second vaccine demonstrated stronger correlation between live viral neutralization titers and both antibody and ACE2 levels, in comparison to those collected earlier.

The SARS-CoV-2 belongs to the coronavirus family, which also includes common endemic coronaviruses (HCoVs). We hypothesized that immunity to HCoVs would be associated with stronger immunogenicity from SARS-CoV-2 vaccines. The study included samples from the COSRIP observational cohort study of adult paramedics in Canada. Participants provided blood samples, questionnaire data, and results of COVID-19 testing. Samples were tested for anti-spike IgG against SARS-CoV-2, HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43 antigens. We first compared samples from vaccinated and unvaccinated participants, to determine which HCoV antibodies were affected by vaccination. We created scatter plots and performed correlation analysis to estimate the extent of the linear relationship between HCoVs and SARS-CoV-2 anti-spike antibodies. Further, using adjusted log-log multiple regression, we modeled the association between each strain of HCoV and SARS-CoV-2 antibodies. Of 1510 participants (mean age of 39 years), 94 (6.2%) had a history of COVID-19. There were significant differences between vaccinated and unvaccinated participant in anti-spike antibodies to HCoV-HKU1, and HCoV-OC43; however, levels for HCoV-229E and HCoV-NL63 were similar (suggesting that vaccination did not affect these baseline values). Among vaccinated individuals without prior COVID-19 infection, SARS-COV-2 anti-spike IgG demonstrated a weak positive relationship between both HCoV-229E (r = 0.11) and HCoV-NL63 (r = 0.12). From the adjusted log-log multiple regression model, higher HCoV-229E and HCoV-NL63 anti-spike IgG antibodies were associated with increased SARS-COV-2 anti-spike IgG antibodies. Vaccination appears to result in measurable increases in HCoV-HKU1, and HCoV-OC43 IgG levels. Anti-HCoV-229E and HCoV-NL63 antibodies were unaffected by vaccination, and higher levels were associated with significantly higher COVID-19 vaccine-induced SARS-COV-2 antibodies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Asamoah-Boaheng, Grunau, Karim, Jassem, Bolster, Marquez, Scheuermeyer and Goldfarb.)

The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17-28 days) vs long (42-49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: With many disease-modifying therapies currently approved for the management of multiple sclerosis, there is a growing need to evaluate the comparative effectiveness and safety of those therapies from real-world data sources. Propensity score methods have recently gained popularity in multiple sclerosis research to generate real-world evidence. Recent evidence suggests, however, that the conduct and reporting of propensity score analyses are often suboptimal in multiple sclerosis studies., Objectives: To provide practical guidance to clinicians and researchers on the use of propensity score methods within the context of multiple sclerosis research., Methods: We summarize recommendations on the use of propensity score matching and weighting based on the current methodological literature, and provide examples of good practice., Results: Step-by-step recommendations are presented, starting with covariate selection and propensity score estimation, followed by guidance on the assessment of covariate balance and implementation of propensity score matching and weighting. Finally, we focus on treatment effect estimation and sensitivity analyses., Conclusion: This comprehensive set of recommendations highlights key elements that require careful attention when using propensity score methods.

Background: Propensity score (PS) analyses are increasingly used in multiple sclerosis (MS) research, largely owing to the greater availability of large observational cohorts and registry databases., Objective: To evaluate the use and quality of reporting of PS methods in the recent MS literature., Methods: We searched the PubMed database for articles published between January 2013 and July 2019. We restricted the search to comparative effectiveness studies of two disease-modifying therapies., Results: Thirty-nine studies were included in the review, with most studies (62%) published within the past 3 years. All studies reported the list of covariates used for the PS model, but only 21% of studies mentioned how those covariates were selected. Most studies used PS matching (72%), followed by PS adjustment (18%), weighting (15%), and stratification (3%), with some overlap. Most studies using matching or weighting reported checking post-PS covariate imbalance (91%), although about 45% of these studies relied on p values from various statistical tests. Only 25% of studies using matching reported calculating robust standard errors for the PS analyses., Conclusions: The quality of reporting of PS methods in the MS literature is sub-optimal in general, and in some cases, inappropriate methods are used.

Study Objective: SARS-CoV-2 represents an occupational risk to paramedics, who work in uncontrolled environments. We sought to identify the occupation-specific risk to paramedics by comparing their seroprevalence of SARS-CoV-2 infection-specific antibodies to that of blood donors in Canada., Methods: In this prospective cohort study, we performed serology testing (Elecsys Anti-SARS-CoV-2 nucleocapsid assay) on samples from paramedics and blood donors (January to July 2021) in Canada. Paramedic samples were compared to blood donor samples through 1:1-matched (based on age, sex, location, date of blood collection, and vaccination status) and raking weighted comparisons. We compared the seroprevalence with a risk difference (and 95% confidence interval [CI]) and performed secondary analyses within subgroups defined by vaccination status., Results: The 1:1 match included 1,627 cases per group; in both groups, 723 (44%) were women, with a median age of 38. The raking weighted comparison included 1,713 paramedic samples and 19,515 blood donor samples, with similar characteristics. In the 1:1 match, the seroprevalence was similar (difference 1.2; 95% CI -0.20 to 2.7) between paramedics (5.2%) and blood donors (3.9%). The raking weighted comparison was consistent (difference 0.97; 95% CI -0.10 to 2.0). The unvaccinated paramedic samples, in comparison to the blood donor samples, demonstrated a higher seroprevalence in the 1:1 (difference 5.9; 95% CI 1.8 to 10) and weighted (difference 6.5; 95% CI 1.8 to 10) comparisons. Among vaccinated cases, the between-group seroprevalence was similar., Conclusion: Overall, paramedics demonstrated similar evidence of prior SARS-CoV-2 infection to that of blood donors. However, among unvaccinated individuals, evidence of prior infection was higher among paramedics compared to blood donors., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)