Diagnostic accuracy of digital technologies compared with 12-lead ECG in the diagnosis of atrial fibrillation in adults: A protocol for a systematic review.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. AF increases the risk of stroke 5-fold, though the risk can be reduced with appropriate treatment. Therefore, early diagnosis is imperative but remains a global challenge. In low-and middle-income countries (LMICs), a lack of diagnostic equipment and under-resourced healthcare systems generate further barriers. The rapid development of digital technologies that are capable of diagnosing AF remotely and cost-effectively could prove beneficial for LMICs. However, evidence is lacking on what digital technologies exist and how they compare in regards to diagnostic accuracy. We aim to systematically review the diagnostic accuracy of all digital technologies capable of AF diagnosis. METHODS: MEDLINE, Embase and Web of Science will be searched for eligible studies. Free text terms will be combined with corresponding index terms where available and searches will not be limited by language nor time of publication. Cohort or cross-sectional studies comprising adult (≥18 years) participants will be included. Only studies that use a 12-lead ECG as the reference test (comparator) and report outcomes of sensitivity, specificity, the diagnostic odds ratio (DOR) or the positive and negative predictive value (PPV and NPV) will be included (or if they provide sufficient data to calculate these outcomes). Two reviewers will independently assess articles for inclusion, extract data using a piloted tool and assess risk of bias using the QUADAS-2 tool. The feasibility of a meta-analysis will be determined by assessing heterogeneity across the studies, grouped by index device, diagnostic threshold and setting. If a meta-analysis is feasible for any index device, pooled sensitivity and specificity will be calculated using a random effect model and presented in forest plots. DISCUSSION: The findings of our review will provide a comprehensive synthesis of the diagnostic accuracy of available digital technologies capable for diagnosing AF. Thus, this review will aid in the identification of which devices could be further trialed and implemented, particularly in a LMIC setting, to improve the early diagnosis of AF. TRIAL REGISTRATION: Systematic review registration: PROSPERO registration number is CRD42021290542. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021290542.

Generalisability of and lessons learned from a mixed-methods study conducted in three low- and middle-income countries to identify care pathways for atrial fibrillation.

BACKGROUND: Identifying existing care pathways is the first step for understanding how services can be improved to enable early diagnosis and effective follow-up care for non-communicable diseases (NCDs); however, evidence on how care pathways can and should be identified in low- and middle-income countries (LMICs) is lacking. OBJECTIVE: To describe generalisability and lessons learned from recruitment and data collection for the quantitative component of a mixed methods study designed to determine the care pathway for atrial fibrillation (AF) in Brazil, China and Sri Lanka. METHODS: Adults (≥18 years) that spoke the local language and with an AF diagnosis were eligible. We excluded anyone with a hearing or cognitive impairment or ineligible address. Eligible participants were identified using electronic records in Brazil and China; in Sri Lanka, researchers attended the outpatient clinics to identify eligible participants. Data were collected using two quantitative questionnaires administered at least 2-months apart. A minimum sample size of 238 was required for each country. RESULTS: The required sample size was met in Brazil (n = 267) and China (n = 298), but a large proportion of AF patients could not be contacted (47% and 27%, respectively) or refused to participate (36% and 38%, respectively). In Sri Lanka, recruitment was challenging, resulting in a reduced sample (n = 151). Mean age of participants from Brazil, China and Sri Lanka was 69 (SD = 11.3), 65 (SD = 12.8) and 58 (SD = 11.7), respectively. Females accounted for 49% of the Brazil sample, 62% in China and 70% in Sri Lanka. CONCLUSIONS: Generalisability was an issue in Brazil and China, as was selection bias. Recruitment bias was highlighted in Sri Lanka. Additional or alternative recruitment methods may be required to ensure generalisability and reduce bias in future studies aimed at identifying NCD care pathways in LMICs.

The impact of rate and rhythm control strategies on quality of life for patients with atrial fibrillation: a protocol for a systematic review.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia globally and it adversely affects the quality of life (QoL). Available rate and rhythm control strategies equally reduce mortality but may impact QoL differently. A number of systematic reviews have focused on the impact of specific strategies on QoL, though a 2006 review synthesized the evidence on the effect of all strategies on QoL, allowing for a clinically important comparison between the types of strategies. Many trials have been published since the review undertook the search in 2005; therefore, an update is needed. This systematic review aims to provide an update to the 2006 review on the impact of all rate and rhythm control strategies on QoL in people with AF. METHODS: The following four databases and three clinical trial registries will be searched for primary studies: CENTRAL, MEDLINE, Embase, CINAHL, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and ClinicalTrialsRegister.eu. No language restriction will be applied. The search will be limited to 2004 or later publication year to allow overlap with the search conducted by the 2006 review authors. Any randomized control trial that reports the QoL of adult (≥ 18 years) AF patients following an eligible rate or rhythm control intervention will be eligible for inclusion. Eligible interventions (and comparators) include pacing, atrioventricular node junction and bundle of HIS ablation, pharmacological therapy, radio frequency catheter ablation, cryoablation, pulmonary vein isolation, maze operation, pace maker implantation, and defibrillator implantation. Two reviewers will independently screen for eligible studies, extract the data using a piloted tool, and assess bias by QoL outcome using the RoB 2 tool. The suitability of conducting a meta-analysis will be assessed by the clinical and methodology similarities of included studies. If it is feasible, standardized mean differences will be pooled using a random-effects model and assessed appropriately. DISCUSSION: The findings from this review will allow for meaningful comparisons between various rate and rhythm control strategies regarding their impact on QoL. This review will be useful for a wide range of stakeholders and will be crucial for optimizing the overall wellbeing of AF patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021290542.

Prevalence of atrial fibrillation in Northern Sri Lanka: a study protocol for a cross-sectional household survey.

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia globally. It is associated with a fivefold risk in stroke, but early diagnosis and effective treatment can reduce this risk. AF is often underdiagnosed, particularly in low-income and middle-income countries (LMICs) where screening for AF is not always feasible or considered common practice in primary care settings. Epidemiological data on AF in LMICs is often incomplete particularly in vulnerable populations. This LMIC research collaborative aims to identify the prevalence of AF in the Northern Sri Lankan community. METHODS AND ANALYSIS: A cross-sectional household survey piloted and codesigned through a series of community engagement events will be administered in all five districts in Northern Province, Sri Lanka. A multistage cluster sampling approach will be used starting at district level, then the Divisional Secretariats followed by Grama Niladhari divisions. Twenty households will be selected from each cluster. The study aims to recruit 10 000 participants aged 50 years or older, 1 participant per household. Demographic and socioeconomic characteristics, well-being and lifestyle and anthropometric measurements will be collected using a digital data platform (REDCap, Research Electronic Data Capture) by trained data collectors. Participants will be screened for AF using a fingertip single-lead ECG via a smartphone application (AliveCor) with rhythm strips reviewed by a consultant cardiologist. Prevalence of AF and risk factors will be established at province and district-levels. Adjusted ORs and population attributable fractions for AF risk factors will be determined. ETHICS AND DISSEMINATION: This study was approved by the Ethics Review Committee of Faculty of Medicine at University of Jaffna. Written informed consent will be obtained from all participants. Findings will be disseminated through publication in a peer-reviewed journal and presentations at conferences. The findings will enable early treatment for new AF diagnoses and inform interventions to improve community-based management of AF in LMICs.

Saúde Cardiovascular e Fibrilação ou Flutter Atrial: Um Estudo Transversal do ELSA-Brasil / Cardiovascular Health and Atrial Fibrillation or Flutter: A Cross-Sectional Study from ELSA-Brasil

Resumo Fundamento A associação entre o status de saúde cardiovascular ideal ( ideal cardiovascular health ( ICVH) e diagnóstico de fibrilação ou flutter atrial (FFA) foi menos estudado em comparação a outras doenças cardiovasculares. Objetivos Analisar a associação entre o diagnóstico de FFA e métricas e escores de ICVH no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Métodos Este estudo analisou dados de 13141 participantes com dados completos. Os traçados eletrocardiográficos foram codificados de acordo com o Sistema de Minnesota, em um centro de leitura centralizado. As métricas do ICVH (dieta, atividade física, índice de massa corporal, tabagismo, glicemia de jeju, e colesterol total) e escores do ICVH foram calculados conforme proposto pela American Heart Association . Modelos de regressão logística bruta e ajustada foram construídos para analisar associações de métricas e escores do ICVH com diagnóstico de FFA. O nível de significância foi estabelecido em 0,05. Resultados A idade mediana da amostra foi de 55 anos, e 54,4% eram mulheres. Nos modelos ajustados, os escores de ICVH não apresentaram associação significativa com diagnóstico de FFA prevalente [odds ratio (OR):0,96; intervalo de confiança de 95% (IC95%):0,80-1,16; p=0,70). Perfis de pressão arterial ideal (OR:0,33; IC95%:0,1-0,74; p=0,007) e colesterol total ideal (OR:1,88; IC95%:1,19-2,98; p=0,007) foram significativamente associados com o diagnóstico de FFA. Conclusões Não foram identificadas associações significativas entre escores de ICVH global e diagnóstico de FFA após ajuste multivariado em nossas análises, devido, ao menos em parte, às associações antagônicas da FFA com métricas de pressão arterial e de colesterol total do ICVH. Nossos resultados sugerem que estimar a prevenção da FFA por meio de escore de ICVH global pode não ser adequado, e as métricas do ICVH devem ser consideradas separadamente.

Abstract Background The association between ideal cardiovascular health (ICVH) status and atrial fibrillation or flutter (AFF) diagnosis has been less studied compared to other cardiovascular diseases. Objective To analyze the association between AFF diagnosis and ICVH metrics and scores in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods This study analyzed data from 13,141 participants with complete data. Electrocardiographic tracings were coded according to the Minnesota Coding System, in a centralized reading center. ICVH metrics (diet, physical activity, body mass index, smoking, blood pressure, fasting plasma glucose, and total cholesterol) and scores were calculated as proposed by the American Heart Association. Crude and adjusted binary logistic regression models were built to analyze the association of ICVH metrics and scores with AFF diagnosis. Significance level was set at 0.05. Results The sample had a median age of 55 years and 54.4% were women. In adjusted models, ICVH scores were not significantly associated with prevalent AFF diagnosis (odds ratio [OR]:0.96; 95% confidence interval [95% CI]:0.80-1.16; p=0.70). Ideal blood pressure (OR:0.33; 95% CI:0.15-0.74; p=0.007) and total cholesterol (OR:1.88; 95% CI:1.19-2.98; p=0.007) profiles were significantly associated with AFF diagnosis. Conclusions No significant associations were identified between global ICVH scores and AFF diagnosis after multivariable adjustment in our analyses, at least partially due to the antagonistic associations of AFF with blood pressure and total cholesterol ICVH metrics. Our results suggest that estimating the prevention of AFF burden using global ICVH scores may not be adequate, and ICVH metrics should be considered in separate.

Cardiovascular Health and Atrial Fibrillation or Flutter: A Cross-Sectional Study from ELSA-Brasil. / Saúde Cardiovascular e Fibrilação ou Flutter Atrial: Um Estudo Transversal do ELSA-Brasil.

BACKGROUND: The association between ideal cardiovascular health (ICVH) status and atrial fibrillation or flutter (AFF) diagnosis has been less studied compared to other cardiovascular diseases. OBJECTIVE: To analyze the association between AFF diagnosis and ICVH metrics and scores in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: This study analyzed data from 13,141 participants with complete data. Electrocardiographic tracings were coded according to the Minnesota Coding System, in a centralized reading center. ICVH metrics (diet, physical activity, body mass index, smoking, blood pressure, fasting plasma glucose, and total cholesterol) and scores were calculated as proposed by the American Heart Association. Crude and adjusted binary logistic regression models were built to analyze the association of ICVH metrics and scores with AFF diagnosis. Significance level was set at 0.05. RESULTS: The sample had a median age of 55 years and 54.4% were women. In adjusted models, ICVH scores were not significantly associated with prevalent AFF diagnosis (odds ratio [OR]:0.96; 95% confidence interval [95% CI]:0.80-1.16; p=0.70). Ideal blood pressure (OR:0.33; 95% CI:0.15-0.74; p=0.007) and total cholesterol (OR:1.88; 95% CI:1.19-2.98; p=0.007) profiles were significantly associated with AFF diagnosis. CONCLUSIONS: No significant associations were identified between global ICVH scores and AFF diagnosis after multivariable adjustment in our analyses, at least partially due to the antagonistic associations of AFF with blood pressure and total cholesterol ICVH metrics. Our results suggest that estimating the prevention of AFF burden using global ICVH scores may not be adequate, and ICVH metrics should be considered in separate.

FUNDAMENTO: A associação entre o status de saúde cardiovascular ideal ( ideal cardiovascular health ( ICVH) e diagnóstico de fibrilação ou flutter atrial (FFA) foi menos estudado em comparação a outras doenças cardiovasculares. OBJETIVOS: Analisar a associação entre o diagnóstico de FFA e métricas e escores de ICVH no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). MÉTODOS: Este estudo analisou dados de 13141 participantes com dados completos. Os traçados eletrocardiográficos foram codificados de acordo com o Sistema de Minnesota, em um centro de leitura centralizado. As métricas do ICVH (dieta, atividade física, índice de massa corporal, tabagismo, glicemia de jeju, e colesterol total) e escores do ICVH foram calculados conforme proposto pela American Heart Association . Modelos de regressão logística bruta e ajustada foram construídos para analisar associações de métricas e escores do ICVH com diagnóstico de FFA. O nível de significância foi estabelecido em 0,05. RESULTADOS: A idade mediana da amostra foi de 55 anos, e 54,4% eram mulheres. Nos modelos ajustados, os escores de ICVH não apresentaram associação significativa com diagnóstico de FFA prevalente [odds ratio (OR):0,96; intervalo de confiança de 95% (IC95%):0,80-1,16; p=0,70). Perfis de pressão arterial ideal (OR:0,33; IC95%:0,1-0,74; p=0,007) e colesterol total ideal (OR:1,88; IC95%:1,19-2,98; p=0,007) foram significativamente associados com o diagnóstico de FFA. CONCLUSÕES: Não foram identificadas associações significativas entre escores de ICVH global e diagnóstico de FFA após ajuste multivariado em nossas análises, devido, ao menos em parte, às associações antagônicas da FFA com métricas de pressão arterial e de colesterol total do ICVH. Nossos resultados sugerem que estimar a prevenção da FFA por meio de escore de ICVH global pode não ser adequado, e as métricas do ICVH devem ser consideradas separadamente.

Healthcare provider and patient perspectives on access to and management of atrial fibrillation in the Northern Province, Sri Lanka: a rapid evaluation of barriers and facilitators to care.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects 60 million people worldwide. Limited evidence on AF management exists from low- and middle-income countries and none from Sri Lanka. We aimed to investigate the existing AF care pathway and patients' perception on AF management to identify barriers and enablers for optimal AF care in Northern Province, Sri Lanka. METHODS: A rapid evaluation was undertaken with use of qualitative methods. Local healthcare providers (HCPs) mapped the intended pathway of care for AF patients which was then explored and annotated through 12 iterative sessions with additional HCPs. Topics of inefficiencies identified from the finalised map were used to guide focus group discussions (FGDs) with AF patients. AF patients who were attending the anticoagulation clinic at the only tertiary hospital in Northern Province were recruited and invited to participate using purposive sampling. The topic guide was developed in collaboration with local clinicians and qualitative experts. FGDs were conducted in the native Tamil language and all sessions were recorded, transcribed verbatim and thematically analysed using a deductive approach. RESULTS: The mapped pathway revealed inefficiencies in referral, diagnosis and ongoing management. These were explored through three FGDs conducted with 25 AF patients aged 25 to 70 years. Two key themes that contributed to and resulted in delays in accessing care and ongoing management were health seeking behaviours and atomistic healthcare structures. Four cross-cutting sub-themes identified were decision making, paternalistic approach to care, cost impacts and lifestyle impacts. These are discussed across 10 unique categories with consideration of the local context. CONCLUSIONS: Strengthening primary healthcare services, improving public health literacy regarding AF and building patient autonomy whilst understanding the importance of their daily life and family involvement may be advantageous in tackling the inefficiencies in the current AF care pathway in Sri Lanka.

Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data.

BACKGROUND: The global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people's diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex. METHODS AND FINDINGS: We linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant's home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual's home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study's key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere. CONCLUSIONS: Our results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

Food environments and obesity: A geospatial analysis of the South Asia Biobank, income and sex inequalities.

INTRODUCTION: In low-middle income countries (LMICs) the role of food environments on obesity has been understudied. We address this gap by 1) examining the effect of food environments on adults' body size (BMI, waist circumference) and obesity; 2) measuring the heterogeneity of such effects by income and sex. METHODS: This cross-sectional study analysed South Asia Biobank surveillance and environment mapping data for 12,167 adults collected between 2018 and 2020 from 33 surveillance sites in Bangladesh and Sri Lanka. Individual-level data (demographic, socio-economic, and health characteristics) were combined with exposure to healthy and unhealthy food environments measured with geolocations of food outlets (obtained through ground-truth surveys) within 300 m buffer zones around participants' homes. Multivariate regression models were used to assess association of exposure to healthy and unhealthy food environments on waist circumference, BMI, and probability of obesity for the total sample and stratified by sex and income. FINDINGS: The presence of a higher share of supermarkets in the neighbourhood was associated with a reduction in body size (BMI, ß = - 3∙23; p < 0∙0001, and waist circumference, ß = -5∙99; p = 0∙0212) and obesity (Average Marginal Effect (AME): -0∙18; p = 0∙0009). High share of fast-food restaurants in the neighbourhood was not significantly associated with body size, but it significantly increased the probability of obesity measured by BMI (AME: 0∙09; p = 0∙0234) and waist circumference (AME: 0∙21; p = 0∙0021). These effects were stronger among females and low-income individuals. INTERPRETATION: The results suggest the availability of fast-food outlets influences obesity, especially among female and lower-income groups. The availability of supermarkets is associated with reduced body size and obesity, but their effects do not outweigh the role of fast-food outlets. Policies should target food environments to promote better diets and reduce obesity.

Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study.

OBJECTIVE: Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS. RESEARCH DESIGN AND METHODS: Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs). RESULTS: The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87). CONCLUSIONS: In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.

Formative research to design an implementation strategy for a postpartum hemorrhage initial response treatment bundle (E-MOTIVE): study protocol.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. When PPH occurs, early identification of bleeding and prompt management using evidence-based guidelines, can avert most PPH-related severe morbidities and deaths. However, adherence to the World Health Organization recommended practices remains a critical challenge. A potential solution to inefficient and inconsistent implementation of evidence-based practices is the application of a 'clinical care bundle' for PPH management. A clinical care bundle is a set of discrete, evidence-based interventions, administered concurrently, or in rapid succession, to every eligible person, along with teamwork, communication, and cooperation. Once triggered, all bundle components must be delivered. The E-MOTIVE project aims to improve the detection and first response management of PPH through the implementation of the "E-MOTIVE" bundle, which consists of (1) Early PPH detection using a calibrated drape, (2) uterine Massage, (3) Oxytocic drugs, (4) Tranexamic acid, (5) Intra Venous fluids, and (6) genital tract Examination and escalation when necessary. The objective of this paper is to describe the protocol for the formative phase of the E-MOTIVE project, which aims to design an implementation strategy to support the uptake of this bundle into practice. METHODS: We will use behavior change and implementation science frameworks [e.g. capability, opportunity, motivation and behavior (COM-B) and theoretical domains framework (TDF)] to guide data collection and analysis, in Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania. There are four methodological components: qualitative interviews; surveys; systematic reviews; and design workshops. We will triangulate findings across data sources, participant groups, and countries to explore factors influencing current PPH detection and management, and potentially influencing E-MOTIVE bundle implementation. We will use these findings to develop potential strategies to improve implementation, which will be discussed and agreed with key stakeholders from each country in intervention design workshops. DISCUSSION: This formative protocol outlines our strategy for the systematic development of the E-MOTIVE implementation strategy. This focus on implementation considers what it would take to support roll-out and implementation of the E-MOTIVE bundle. Our approach therefore aims to maximize internal validity in the trial alongside future scalability, and implementation of the E-MOTIVE bundle in routine practice, if proven to be effective. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04341662.

Excessive bleeding after birth is the leading cause of maternal death globally. The World Health Organization (WHO) has recommended several treatment options for bleeding after birth. However, these treatments are not used regularly, or consistently for all women. A key underlying issue is that it is challenging for health workers to identify when women are bleeding too much, because measuring the amount of blood loss is difficult.Maternal health experts have proposed a new clinical 'care bundle' for caring for women with excessive bleeding after birth. A care bundle is a way to group together multiple treatments (e.g. 3­5 treatments). These treatments are then given to the woman at the same time, or one after another in quick succession, and supported by strategies to improve teamwork, communication, and cooperation.This is a research protocol for the preliminary phase of our study ("E-MOTIVE"), which means that it is a description of what we plan to do and how we plan to do it. The aim of our study is to develop a strategy for how we will test whether the E-MOTIVE bundle works through collaborative activities with midwives and doctors in five countries (Kenya, Nigeria, South Africa, Sri Lanka, and Tanzania) to develop a strategy for how we will test whether the E-MOTIVE bundle works. We plan to do this by conducting interviews and surveys with midwives and doctors, and reviewing other research conducted on PPH to understand what works in different settings. We will discuss our research findings in a workshop, with midwives and doctors in the study countries to co-create a strategy that will work for them, based on their needs and preferences.

Low uptake of COVID-19 prevention behaviours and high socioeconomic impact of lockdown measures in South Asia: Evidence from a large-scale multi-country surveillance programme.

BACKGROUND: South Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians' awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. METHODS: We assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. RESULTS: Participants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P < 0.001), and household income fell by 52% (P < 0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P < 0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P < 0.001), during the lockdown. CONCLUSIONS: Our results identified important knowledge, access and uptake barriers to the prevention of COVID-19 in South Asia, and demonstrated major adverse impacts of the pandemic on chronic disease treatment, mental health, health-related behaviours, employment and household finances. We found important sociodemographic differences for impact, suggesting a widening of existing inequalities. Our findings underscore the need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention, along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor.

Increased risk of obstructive sleep apnoea in women with polycystic ovary syndrome: a population-based cohort study.

OBJECTIVE: Obesity is very common in patients with obstructive sleep apnoea (OSA) and polycystic ovary syndrome (PCOS). Longitudinal studies assessing OSA risk in PCOS and examining the role of obesity are lacking. Our objective was to assess the risk of OSA in women with vs without PCOS and to examine the role of obesity in the observed findings. DESIGN: Population-based retrospective cohort study utilizing The Health Improvement Network (THIN), UK. METHODS: 76 978 women with PCOS and 143 077 age-, BMI- and location-matched women without PCOS between January 2000 and May 2017 were identified. Hazard ratio (HR) for OSA among women with and without PCOS were calculated after controlling for confounding variables using multivariate Cox models. RESULTS: Median patient age was 30 (IQR: 25-35) years; median follow-up was 3.5 (IQR: 1.4-7.1) years. We found 298 OSA cases in PCOS women vs 222 in controls, with incidence rates for OSA of 8.1 and 3.3 per 10 000 person years, respectively. Women with PCOS were at increased risk of developing OSA (adjusted HR = 2.26, 95% CI: 1.89-2.69, P < 0.001), with similar HRs for normal weight, overweight and obese PCOS women. CONCLUSIONS: Women with PCOS are at increased risk of developing OSA compared to control women irrespective of obesity. Considering the significant metabolic morbidity associated with OSA, clinicians should have a low threshold to test for OSA in women with PCOS. Whether OSA treatment has an impact on PCOS symptoms and outcomes needs to be examined.

Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort.

OBJECTIVE: Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex-specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study. DESIGN: A retrospective cohort study in a UK primary care database. PATIENTS: We included men and women with available serum testosterone and sex hormone-binding globulin (SHBG) results. MEASUREMENTS: We categorized serum concentrations according to clinically relevant cut-off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs). RESULTS: Serum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34-3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55-2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively. CONCLUSIONS/INTERPRETATION: In this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively.

Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database.

BACKGROUND: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. METHODS AND FINDINGS: We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86-2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16-4.53, p = 0.017 for 3-3.49 nmol/L and HR = 2.40, 95% CI 1.24-4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI 2.44-9.25, p < 0.001 for 20-29.99 nmol/L and HR = 4.98, 95% CI 2.45-10.11, p < 0.001 for <20 nmol/L). Limitations of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. CONCLUSIONS: We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.

Cluster-randomised trial of the impact of school-based deworming and iron supplementation on the cognitive abilities of schoolchildren in Sri Lanka's plantation sector.

OBJECTIVE: To assess the impact of deworming and iron supplementation on the cognitive abilities and educational achievement of school-age children in Sri Lanka. METHODS: Prospective, placebo-controlled randomised study. The treatment group received deworming and weekly iron supplementation for 6 months; the control group received placebo for both the anthelmintic and iron. A mixed effects regression model was used to answer the main research question. To increase the precision of this study's estimates, various background variables were controlled for that were not related to treatment but could have some impact on the outcome. RESULTS: The prevalence of soil-transmitted helminth (STH) infection was reduced in the treatment group (n = 615), with significant differences between treatment and control groups (n = 575) in the levels of Ascaris and Trichuris. No impact was found on haemoglobin (Hb) levels, nor any significant impact on concentration levels or on educational test scores. CONCLUSION: Decline in STH prevalence alone, in the absence of improved Hb status, produced no evidence of impact on concentration levels or educational test scores.

Analysis of effects of meteorological factors on dengue incidence in Sri Lanka using time series data.

In tropical and subtropical regions of eastern and South-eastern Asia, dengue fever (DF) and dengue hemorrhagic fever (DHF) outbreaks occur frequently. Previous studies indicate an association between meteorological variables and dengue incidence using time series analyses. The impacts of meteorological changes can affect dengue outbreak. However, difficulties in collecting detailed time series data in developing countries have led to common use of monthly data in most previous studies. In addition, time series analyses are often limited to one area because of the difficulty in collecting meteorological and dengue incidence data in multiple areas. To gain better understanding, we examined the effects of meteorological factors on dengue incidence in three geographically distinct areas (Ratnapura, Colombo, and Anuradhapura) of Sri Lanka by time series analysis of weekly data. The weekly average maximum temperature and total rainfall and the total number of dengue cases from 2005 to 2011 (7 years) were used as time series data in this study. Subsequently, time series analyses were performed on the basis of ordinary least squares regression analysis followed by the vector autoregressive model (VAR). In conclusion, weekly average maximum temperatures and the weekly total rainfall did not significantly affect dengue incidence in three geographically different areas of Sri Lanka. However, the weekly total rainfall slightly influenced dengue incidence in the cities of Colombo and Anuradhapura.

Soil-transmitted helminth infections among plantation sector schoolchildren in Sri Lanka: prevalence after ten years of preventive chemotherapy.

BACKGROUND: The plantation sector in Sri Lanka lags behind the rest of the country in terms of living conditions and health. In 1992, a sector-wide survey of children aged 3-12 years and women of reproductive age showed >90% prevalence of soil-transmitted helminth infections. Biannual mass de-worming targeting children aged 3-18 years started in 1994 and was continued until 2005. The present study was carried out to assess the status of infection four years after cessation of mass de-worming. METHODS/FINDINGS: A school-based cross-sectional survey was carried out. Faecal samples from approximately 20 children from each of 114 schools in five districts were examined using the modified Kato-Katz technique. Data regarding the school, the child's family and household sanitation were recorded after inspection of schools and households. Multivariate analysis was carried out using logistic regression, to identify risk factors for infection. Faecal samples were obtained from 1890 children. In 4/5 districts, >20% were infected with one or more helminth species. Overall combined prevalence was 29.0%; 11.6% had infections of moderate-heavy intensity. The commonest infection was Ascaris lumbricoides, present in all five districts, as was Trichuris trichiura. Hookworm was not detected in two districts. Multivariate analysis identified low altitude and maternal under-education as risk factors for all three infections. Poor household sanitation was identified as a risk factor for A. lumbricoides and hookworm, but not T. trichiura infections. CONCLUSIONS/SIGNIFICANCE: The results indicate that regular mass de-worming of plantation sector children should be resumed along with more emphasis on better sanitation and health education. They show that even after 10 years of mass chemotherapy, prevalence can bounce back after cessation of preventive chemotherapy, if the initial force of transmission is strong and other long-term control measures are not concomitantly implemented.