69832 research outputs found
Sort by
Overcoming time-varying confounding in self-controlled case series with active comparators: application and recommendations.
Get PDFConfounding by indication is a key challenge for pharmacoepidemiologists. Although self-controlled study designs address time-invariant confounding, indications sometimes vary over time. For example, infection might act as a time-varying confounder in a study of antibiotics and uveitis, because it is time-limited and a direct cause of both receipt of antibiotics and uveitis. Methods for incorporating active comparators in self-controlled studies to address such time-varying confounding by indication have only recently been developed. In this paper, we formalize these methods and provide a detailed description for how the active comparator rate ratio can be derived in a self-controlled case series: either by explicitly comparing the regression coefficients for a drug of interest and an active comparator under certain circumstances using a simple ratio approach or through the use of a nested regression model. The approaches are compared in 2 case studies, one examining the association between thiazolidinedione use and fractures and one examining the association between fluoroquinolone use and uveitis, using the United Kingdom's Clinical Practice Research Datalink. Finally, we provide recommendations for the use of these methods, which we hope will support the design, execution, and interpretation of self-controlled case series using active comparators and thereby increase the robustness of pharmacoepidemiologic studies. This article is part of a Special Collection on Pharmacoepidemiology
High resolution mapping of nitrogen dioxide and particulate matter in Great Britain (2003-2021) with multi-stage data reconstruction and ensemble machine learning methods.
Get PDFIn this contribution, we applied a multi-stage machine learning (ML) framework to map daily values of nitrogen dioxide (NO2) and particulate matter (PM10 and PM2.5) at a 1 km2 resolution over Great Britain for the period 2003-2021. The process combined ground monitoring observations, satellite-derived products, climate reanalyses and chemical transport model datasets, and traffic and land-use data. Each feature was harmonized to 1 km resolution and extracted at monitoring sites. Models used single and ensemble-based algorithms featuring random forests (RF), extreme gradient boosting (XGB), light gradient boosting machine (LGBM), as well as lasso and ridge regression. The various stages focused on augmenting PM2.5 using co-occurring PM10 values, gap-filling aerosol optical depth and columnar NO2 data obtained from satellite instruments, and finally the training of an ensemble model and the prediction of daily values across the whole geographical domain (2003-2021). Results show a good ensemble model performance, calculated through a ten-fold monitor-based cross-validation procedure, with an average R2 of 0.690 (range 0.611-0.792) for NO2, 0.704 (0.609-0.786) for PM10, and 0.802 (0.746-0.888) for PM2.5. Reconstructed pollution levels decreased markedly within the study period, with a stronger reduction in the latter eight years. The pollutants exhibited different spatial patterns, while NO2 rose in close proximity to high-traffic areas, PM demonstrated variation at a larger scale. The resulting 1 km2 spatially resolved daily datasets allow for linkage with health data across Great Britain over nearly two decades, thus contributing to extensive, extended, and detailed research on the long-and short-term health effects of air pollution
Interventions for tobacco use cessation in people living with HIV.
Get PDFBACKGROUND: The prevalence of tobacco use among people living with HIV (PLWH) is up to four times higher than in the general population. Unfortunately, tobacco use increases the risk of progression to AIDS and death. Individual- and group-level interventions, and system-change interventions that are effective in helping PLWH stop using tobacco can markedly improve the health and quality of life of this population. However, clear evidence to guide policy and practice is lacking, which hinders the integration of tobacco use cessation interventions into routine HIV care. This is an update of a review that was published in 2016. We include 11 new studies. OBJECTIVES: To assess the benefits, harms and tolerability of interventions for tobacco use cessation among people living with HIV. To compare the benefits, harms and tolerability of interventions for tobacco use cessation that are tailored to the needs of people living with HIV with that of non-tailored cessation interventions. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO in December 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of individual-/group-level behavioural or pharmacological interventions, or both, for tobacco use cessation, delivered directly to PLWH aged 18 years and over, who use tobacco. We also included RCTs, quasi-RCTs, other non-randomised controlled studies (e.g. controlled before and after studies), and interrupted time series studies of system-change interventions for tobacco use cessation among PLWH. For system-change interventions, participants could be PLWH receiving care, or staff working in healthcare settings and providing care to PLWH; but studies where intervention delivery was by research personnel were excluded. For both individual-/group-level interventions, and system-change interventions, any comparator was eligible. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods, and used GRADE to assess certainty of the evidence. The primary measure of benefit was tobacco use cessation at a minimum of six months. Primary measures for harm were adverse events (AEs) and serious adverse events (SAEs). We also measured quit attempts or quit episodes, the receipt of a tobacco use cessation intervention, quality of life, HIV viral load, CD4 count, and the incidence of opportunistic infections. MAIN RESULTS: We identified 17 studies (16 RCTs and one non-randomised study) with a total of 9959 participants; 11 studies are new to this update. Nine studies contributed to meta-analyses (2741 participants). Fifteen studies evaluated individual-/group-level interventions, and two evaluated system-change interventions. Twelve studies were from the USA, two from Switzerland, and there were single studies for France, Russia and South Africa. All studies focused on cigarette smoking cessation. All studies received funding from independent national- or institutional-level funding. Three studies received study medication free of charge from a pharmaceutical company. Of the 16 RCTs, three were at low risk of bias overall, five were at high risk, and eight were at unclear risk. Behavioural support or system-change interventions versus no or less intensive behavioural support Low-certainty evidence (7 studies, 2314 participants) did not demonstrate a clear benefit for tobacco use cessation rates in PLWH randomised to receive behavioural support compared with brief advice or no intervention: risk ratio (RR) 1.11, 95% confidence interval (CI) 0.87 to 1.42, with no evidence of heterogeneity. Abstinence at six months or more was 10% (n = 108/1121) in the control group and 11% (n = 127/1193) in the intervention group. There was no evidence of an effect on tobacco use cessation on system-change interventions: calling the quitline and transferring the call to the patient whilst they are still in hospital ('warm handoff') versus fax referral (RR 3.18, 95% CI 0.76 to 13.99; 1 study, 25 participants; very low-certainty evidence). None of the studies in this comparison assessed SAE. Pharmacological interventions versus placebo, no intervention, or another pharmacotherapy Moderate-certainty evidence (2 studies, 427 participants) suggested that varenicline may help more PLWH to quit smoking than placebo (RR 1.95, 95% CI 1.05 to 3.62) with no evidence of heterogeneity. Abstinence at six months or more was 7% (n = 14/215) in the placebo control group and 13% (n = 27/212) in the varenicline group. There was no evidence of intervention effects from individual studies on behavioural support plus nicotine replacement therapy (NRT) versus brief advice (RR 8.00, 95% CI 0.51 to 126.67; 15 participants; very low-certainty evidence), behavioural support plus NRT versus behavioural support alone (RR 1.47, 95% CI 0.92 to 2.36; 560 participants; low-certainty evidence), varenicline versus NRT (RR 0.93, 95% CI 0.48 to 1.83; 200 participants; very low-certainty evidence), and cytisine versus NRT (RR 1.18, 95% CI 0.66 to 2.11; 200 participants; very low-certainty evidence). Low-certainty evidence (2 studies, 427 participants) did not detect a difference between varenicline and placebo in the proportion of participants experiencing SAEs (8% (n = 17/212) versus 7% (n = 15/215), respectively; RR 1.14, 95% CI 0.58 to 2.22) with no evidence of heterogeneity. Low-certainty evidence from one study indicated similar SAE rates between behavioural support plus NRT and behavioural support only (1.8% (n = 5/279) versus 1.4% (n = 4/281), respectively; RR 1.26, 95% CI 0.34 to 4.64). No studies assessed SAEs for the following: behavioural support plus NRT versus brief advice; varenicline versus NRT and cytisine versus NRT. AUTHORS' CONCLUSIONS: There is no clear evidence to support or refute the use of behavioural support over brief advice, one type of behavioural support over another, behavioural support plus NRT over behavioural support alone or brief advice, varenicline over NRT, or cytisine over NRT for tobacco use cessation for six months or more among PLWH. Nor is there clear evidence to support or refute the use of system-change interventions such as warm handoff over fax referral, to increase tobacco use cessation or receipt of cessation interventions among PLWH who use tobacco. However, the results must be considered in the context of the small number of studies included. Varenicline likely helps PLWH to quit smoking for six months or more compared to control. We did not find evidence of difference in SAE rates between varenicline and placebo, although the certainty of the evidence is low
WHO global research priorities for antimicrobial resistance in human health.
Get PDFThe WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR
Correlates of Sleep Health among Older-Age People with and without HIV in Uganda.
Get PDFThere is a growing population of older people with HIV (PWH) in Uganda. Sleep problems disproportionately affect older people and PWH. This study aimed to estimate correlates of sleep health among older Ugandans (aged ≥ 50 years) with and without HIV, using data from the Quality of Life and Aging with HIV in Rural Uganda Study. We used the Pittsburgh Sleep Quality Index to assess sleep quality, duration, and efficiency. We fitted multivariable linear and logistic regression models to estimate the associations between sleep outcomes and variables selected based on the Senescent Sleep Model: age, HIV serostatus, loneliness, urbanicity, symptoms of depression and anxiety, and perceived stress. Of 556 participants, 271 were PWH and 285 were people without HIV (PWoH). There were no statistically significant differences in sleep outcomes by HIV serostatus. Of the total sample, most reported very good (32.79%) or fairly good sleep quality (49.37%). The mean sleep duration was 6.46 h (SD = 1.74). The mean sleep efficiency was 73.98% (SD = 19.52%) with 36.69% having optimal (≥ 85%) sleep efficiency. A positive depression screen was associated with worse sleep quality (adjusted odds ratio [aOR] = 0.21; 95% CI [0.12, 0.36]), shorter sleep duration (b=-0.44; 95% CI [-0.60, -0.28]), and worse sleep efficiency (aOR = 0.51; 95% CI[0.31, 0.83]). Interventions targeting depression may improve sleep among older Ugandans, independent of HIV serostatus. Longitudinal studies are needed to determine the potential bidirectionality of this relationship and elucidate pathways to support sleep health among older Ugandans
Microbes and marginalisation: ‘Facing’ antimicrobial resistance in bedridden patients in a peri-urban area of Thailand
Get PDFReducing human-microbial encounters through improved infection prevention and control (IPC) is widely acknowledged to be critical for reducing the emergence, transmission and burden of antimicrobial resistance (AMR). However, despite its centrality in the Global Action Plan (GAP) on AMR and adoption as a goal in National Action Plans around the world, there has been limited progress on reducing the incidence of antimicrobial resistant infections globally. In this paper, we argue that closer attention to different faces of AMR could propel progress in this area, with a focus on bedridden people situated in liminal spaces in the Thai health system and suburban economy. Our ethnographic fieldwork followed the cases of 16 bedridden people through the eyes of their carers and medical staff. We 'descended into the ordinary' to encounter individuals living - and dying - in the shadows of the labour-intensive suburbs of Bangkok. Here, AMR and IPC protocols are operationalised in the context of competing priorities and pragmatic decision-making. Focussing on three ethnographic vignettes, we use the analytic frames of precarity and care to consider how particular (bedridden) bodies are differentially exposed to AMR infections in the context of economic, social, and political arrangements that structure embodied vulnerabilities and forms and foci of care. Whilst the political work of calculating the burden of AMR may be oriented around galvanising support through a sense of magnitude and generalised risk, this research serves as a reminder that the faces of AMR include those who disproportionately shoulder the global burden of AMR, making it at once exceptional and ordinary
Predicting mortality in febrile adults: comparative performance of the MEWS, qSOFA, and UVA scores using prospectively collected data among patients in four health-care sites in sub-Saharan Africa and South-Eastern Asia.
No full textBACKGROUND: Clinical severity scores can identify patients at risk of severe disease and death, and improve patient management. The modified early warning score (MEWS), the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and the Universal Vital Assessment (UVA) were developed as risk-stratification tools, but they have not been fully validated in low-resource settings where fever and infectious diseases are frequent reasons for health care seeking. We assessed the performance of MEWS, qSOFA, and UVA in predicting mortality among febrile patients in the Lao PDR, Malawi, Mozambique, and Zimbabwe. METHODS: We prospectively enrolled in- and outpatients aged ≥ 15 years who presented with fever (≥37.5 °C) from June 2018-March 2021. We collected clinical data to calculate each severity score. The primary outcome was mortality 28 days after enrolment. The predictive performance of each score was determined using area under the receiver operating curve (AUC). FINDINGS: A total of 2797 participants were included in this analysis. The median (IQR) age was 32 (24-43) years, 38% were inpatients, and 60% (1684/2797) were female. By the time of follow-up, 7% (185/2797) had died. The AUC (95% CI) for MEWS, qSOFA and UVA were 0.67 (0.63-0.71), 0.68 (0.64-0.72), and 0.82 (0.79-0.85), respectively. The AUC comparison found UVA outperformed both MEWS (p < 0.001) and qSOFA (p < 0.001). INTERPRETATION: We showed that the UVA score performed best in predicting mortality among febrile participants by the time follow-up compared with MEWS and qSOFA, across all four study sites. The UVA score could be a valuable tool for early identification, triage, and initial treatment guidance of high-risk patients in resource-limited clinical settings. FUNDING: FCDO
A systematic review of environmental covariates and methods for spatial or temporal scrub typhus distribution prediction.
Get PDFBACKGROUND: Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. To inform future burden and prediction studies we examined through a systematic review the potential effect of environmental covariates on scrub typhus occurrence and the methods which have been used for its prediction. METHODS: In this systematic review, we searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases, with no language and publication time restrictions, for studies that investigated environmental covariates or utilized methods to predict the spatial or temporal human. Data were manually extracted following a set of queries and systematic analysis was conducted. RESULTS: We included 68 articles published in 1978-2024 with relevant data from 7 countries/regions. Significant environmental risk factors for scrub typhus include temperature (showing positive or inverted-U relationships), precipitation (with positive or inverted-U patterns), humidity (exhibiting complex positive, inverted-U, or W-shaped associations), sunshine duration (with positive, inverted-U associations), elevation, the normalized difference vegetation index (NDVI), and the proportion of cropland. Socioeconomic and biological factors were rarely explored. Autoregressive Integrated Moving Average (ARIMA) (n = 8) and ecological niche modelling (ENM) approach (n = 11) were the most popular methods for predicting temporal trends and spatial distribution of scrub typhus, respectively. CONCLUSIONS: Our findings summarized the evidence on environmental covariates affecting scrub typhus occurrence and the methodologies used for predictive modelling. We review the existing knowledge gaps and outline recommendations for future studies modelling disease prediction and burden. TRIAL REGISTRATION: PROSPERO CRD42022315209
Dataset of 16S rRNA gene sequences of 111 healthy and Newcastle disease infected caecal samples from multiple chicken breeds of Pakistan.
Get PDFThe article presents a processed dataset from amplicon sequencing of the V4 region of the 16S rRNA gene to recover bacterial and archaeal taxa from the caeca of multiple chicken breeds of Pakistan. These include chicken breeds commonly raised at commercial level, Naked Neck, Black Australorp, Rhode Island Red, White Layer, and Broiler. All the breeds were challenged with Newcastle Disease Virus (NDV), with vaccination against the disease also explored. This resulted in samples belonging to four treatment groups as: Control; Vaccinated; Vaccinated and Challenged; and Non-vaccinated and Challenged. These were raised on an antibiotic free diet in a semi-controlled farming setup. 16S rRNA gene amplicon sequencing of caecal DNA from day old and mature chicken samples (22 weeks for Naked Neck, Black Australorp, Rhode Island Red and White Layer; 8 weeks for Broiler) of the four groups was performed. The paired-end reads from all the samples were quality trimmed, error corrected, and overlapped, on which unique Operational Taxonomic Units (OTUs) were obtained at 99 % similarity. Using predictive modelling, the MetaCyc functional pathways, as well as KEGG orthologs were also recovered. The generated data may be used to explore microbial interactions in gastrointestinal tract with respect to NDV vaccination and infection, together with increased understanding of chicken health and productivity
Prevalence and management of ectopic and molar pregnancies in 17 countries in Africa and Latin America and the Caribbean: a secondary analysis of the WHO multi-country cross-sectional survey on abortion.
Get PDFINTRODUCTION: There are limited global data on ectopic pregnancy (EP) and molar pregnancy (MP), making it important to understand their epidemiology and management across different regions. Our study aimed to describe their prevalence for both conditions, severity of their complications and management among women in selected health facilities across 17 countries in Africa and Latin America and the Caribbean (LAC). METHODS: This is a secondary analysis of the WHO multi-country survey on abortion. Data were collected from 280 healthcare facilities across 11 countries in Africa and 6 in LAC. Sociodemographic information, signs and symptoms, management and clinical outcomes were extracted from medical records. Facility-level data on post-abortion care (PAC) capabilities were also collected, and facilities were classified accordingly. χ2 or Fisher's exact tests were used to compare categorical data. RESULTS: The total number of women with EP and MP across both regions was 9.9% (2 415/24 424) where EP accounted for 7.8% (1 904/24 424) and MP for 2.1% (511/24 424). EP presented a higher severity of complications than MP. At admission, 49.8% of EP had signs of peritoneal irritation. The most common surgical management for EP was laparotomy (87.2%) and for MP, uterine evacuation (89.8%). Facilities with higher scores in infrastructure and capability to provide PAC more frequently provided minimal invasive management using methotrexate/other medical treatment (34.9%) and laparoscopy (5.1%). CONCLUSION: In Africa and LAC, EP and MP cause significant maternal morbidity and mortality. The disparity in the provision of good quality care highlights the need to strengthen the implementation of evidence-based recommendations in the clinical and surgical management of EP and MP