Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.

AIMS: To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care. METHODS: A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation. RESULTS: Of the 2.3 million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90 mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58 mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5 mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97). CONCLUSIONS: There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.

The association between menstrual cycle characteristics and cardiometabolic outcomes in later life: a retrospective matched cohort study of 704,743 women from the UK.

BACKGROUND: Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk. METHODS: A UK retrospective cohort study (1995-2021) using data from a nationwide database (The Health Improvement Network). Women aged 18-40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls. RESULTS: During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00-1.19), IHD 1.18 (1.01-1.37), cerebrovascular disease 1.04 (0.92-1.17), HF 1.30 (1.02-1.65), hypertension 1.07 (1.03-1.11), T2DM 1.37 (1.29-1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02-1.52), IHD 1.13 (0.81-1.57), cerebrovascular disease 1.43 (1.10-1.87), HF 0.99 (0.57-1.75), hypertension 1.31 (1.21-1.43), T2DM 1.74 (1.52-1.98). CONCLUSIONS: History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.

A matched cohort study investigating premature, accentuated, and accelerated aging in people living with HIV.

INTRODUCTION: The impact of HIV infection on the aging process is disputed and largely unknown. We aimed to identify whether people living with HIV experience premature, accelerated, and/or accentuated aging by investigating the development of four age-related non-communicable diseases in people living with versus without HIV. METHODS: This population-based matched cohort study design used UK-based primary care electronic health records from the IQVIA Medical Research Database. Between January 2000 and January 2020, all people living with and without HIV aged ≥18 years were eligible. Outcomes included cardiovascular disease (CVD), hypertension, type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), which were identified by Read codes. We used age at diagnosis to investigate premature aging and age at exit date to investigate accentuation and acceleration. For each outcome, people with and without HIV were excluded if they had the outcome of interest at baseline. Participants were matched based on propensity scores (1:1 ratio). Linear regression was used to report any difference in age at diagnosis between the two groups and to report the prevalence trends for age at exit date. RESULTS: In total, 8880 people living with HIV were matched with 8880 people without HIV and were found to have an earlier onset of CVD (54.5 vs. 56.8; p = 0.002). Similarly, people living with HIV had an earlier onset of hypertension (49.7 vs. 51.4; p = 0.002). No difference was found for T2DM or CKD (53.4 vs. 52.6; p = 0.368 and 57.6 vs. 58.1; p = 0.483, respectively). The burden of CKD increased over time, whereas no difference in the burden was found for the other conditions. CONCLUSION: The earlier development of CVD and hypertension in people living with HIV than in those without HIV indicates premature aging, whereas the increased burden of CKD indicates accelerated aging.

Timing of infant formula introduction in relation to BMI and overweight at ages 1 and 3 years: the Born in Guangzhou Cohort Study (BIGCS).

Mounting evidence suggests that the first few months of life are critical for the development of obesity. The relationships between the timing of solid food introduction and the risk of childhood obesity have been examined previously; however, evidence for the association of timing of infant formula introduction remains scarce. This study aimed to examine whether the timing of infant formula introduction is associated with growth z-scores and overweight at ages 1 and 3 years. This study included 5733 full-term (≥ 37 gestational weeks) and normal birth weight (≥ 2500 and < 4000 g) children in the Born in Guangzhou Cohort Study, a prospective cohort study with data collected at 6 weeks, 6, 12 and 36 months. Compared with infant formula introduction at 0-3 months, introduction at 4-6 months was associated with the lower BMI, weight-for-age and weight-for-length z-scores at 1 and 3 years old. Also, introduction at 4-6 months was associated with the lower odds of at-risk of overweight at age 1 (adjusted OR 0·72, 95 % CI 0·55, 0·94) and 3 years (adjusted OR 0·50, 95 % CI 0·30, 0·85). Introduction at 4-6 months also decreased the odds of overweight at age 1 year (adjusted OR 0·42, 95 % CI 0·21, 0·84) but not at age 3 years. Based on our findings, compared with introduction within the first 3 months, introduction at 4-6 months has a reduction on later high BMI risk and at-risk of overweight. However, these results need to be replicated in other well-designed studies before more firm recommendations can be made.

Safety and efficacy of tuberculosis vaccine candidates in low- and middle-income countries: a systematic review of randomised controlled clinical trials.

BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide, with 98% of cases occurring in low- and middle-income countries (LMICs). The only vaccine licenced for the prevention of TB has limited protection for adolescents, adults and vulnerable populations. A safe and effective vaccine for all populations at risk is imperative to achieve global elimination of TB. We aimed to systematically review the efficacy and safety of TB vaccine candidates in late-phase clinical trials conducted in LMICs. METHODS: Medline, Embase, CENTRAL, PubMed, Clinicaltrials.gov and Greylit.org were searched in June 2021 to identify phase 2 or later clinical randomised controlled trials that report the efficacy or safety (adverse events) of TB vaccine candidates with participants of any age living in an LMIC. TB vaccine candidates listed in the 2020 WHO Global TB Report were eligible for inclusion aside from BCG revaccination. Trials were excluded if all participants had active TB at baseline. Two reviewers independently assessed papers for eligibility, and for bias and quality using the Risk of Bias 2 tool and GRADE guidelines, respectively. We report efficacy rates and frequencies of adverse events from each included trial where available and qualitatively synthesise the findings. RESULTS: Thirteen papers representing eleven trials met our inclusion criteria. Seven vaccine candidates were reviewed across seven countries: M72/AS01, RUTI, VPM1002, H56:IC31, MTBVAC, DAR-901 and ID93 + GLA-SE. Two trials reported on efficacy: an efficacy rate of 54% (95% CI 11.5, 76.2) was reported for M72/AS01 in adults with latent TB and 3% (95% CI -13.9, 17.7) for DAR-901 in healthy adolescents. However, the latter trial was underpowered. All vaccine candidates had comparable occurrences of adverse events between treatment arms and demonstrated acceptable safety profiles; though, RUTI resulted in one serious complication in a person living with HIV. M72/AS01 was the only vaccine considered safe across a diverse group of people including people living with HIV or latent TB and healthy infants and adolescents. CONCLUSION: Further efficacy trials for M72/AS01 are warranted to include additional populations at risk where safety has been demonstrated. Further safety trials are needed for the remaining vaccine candidates to confirm safety in vulnerable populations.

Cereal intake and mortality in older Chinese: a 15-year follow-up of a prospective cohort study.

PURPOSE: We examined the association between whole grain and refined grain intake with all-cause, cancer and cardiovascular disease (CVD) mortality using the data from the Guangzhou Biobank Cohort Study. METHODS: 19,597 participants aged 50+ years were recruited from 2003 to 2006 and followed-up until April 2021. Multivariable Cox regression was used to calculate hazard radios (HRs) and 95% confidence intervals (CIs). Substitution analysis was used to replace a serving (50 g/day) of whole grain with a serving of refined grain. RESULTS: During 286,821 person-years of follow-up, 4385 deaths occurred, including 1450 from cancer, 1678 from CVD and 1257 from other causes. Compared with never whole grain intake, the highest intake category of whole grain (> 300 g/week) was associated with lower risk of all-cause (HR 0.90, 95% CI 0.82-0.98) and CVD mortality (HR 0.85, 0.74-0.98). Compared with the low-intake category of refined grain (< 500 g/day), the highest intake category (> 900 g/week) was associated with a lower risk of cancer mortality (HR 0.76, 0.62-0.95), but a higher risk of CVD mortality (HR 1.25, 1.03-1.51). No significant associations were found between whole grain intake and cancer mortality nor refined grain and all-cause mortality. The HRs of all-cause, cancer and CVD mortality substituting a serving of whole grain for refined grain were 0.96 (0.94-0.99), 1.01 (0.99-1.02) and 0.95 (0.90-0.99), respectively. CONCLUSION: We have first shown that in older Chinese, whole grain intake was associated with lower risk of all-cause and CVD mortality. Our results suggest that intake of whole grain of at least 300 g/week and refined grain of ≤ 900 g/day might be suitable for older Asian. Substituting 50 g/day of whole grain for refined grain was associated with a 4-5% lower risk of all-cause and CVD mortality.

Risk of cardiometabolic outcomes among women with a history of pelvic inflammatory disease: a retrospective matched cohort study from the UK.

INTRODUCTION: To describe the incidence and prevalence of pelvic inflammatory disease (PID) and to estimate the risk of cardiometabolic outcomes among women with PID compared to women without PID. METHODS: A UK retrospective matched cohort study using data from The Health Improvement Network. To assess cardiometabolic risk, women (aged ≥ 16 years) with PID were compared to matched controls without PID. Annual prevalence and incidence of PID (1998-2017) were estimated among women aged 16-50 years using annual cross-sectional and cohort analyses, respectively. Adjusted hazard ratios (aHR) and 95% CI for cardiometabolic outcomes were estimated using Cox proportional hazards models. The primary outcome was composite cardiovascular disease (CVD) and its subtypes, including ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were hypertension, and type 2 diabetes mellitus (T2DM). RESULTS: Among the 715 recorded composite CVD events, the crude incidence rate per 1000 person-years was 1.5 among women with history of PID compared to 1.3 in matched controls. Compared to women without PID (N = 73,769), the aHRs for cardiometabolic outcomes among women with PID (N = 19,804) were: composite CVD 1.10 (95% CI 0.93-1.30); IHD 1.19 (95% CI 0.93-1.53); cerebrovascular disease 1.13 (95% CI 0.90-1.43); HF 0.92 (95% CI 0.62-1.35) hypertension 1.10 (95% CI 1.01-1.20); and T2DM 1.25 (95% CI 1.09-1.43). The prevalence (per 10,000 population) of PID was 396.5 in 1998 and 237 in 2017. The incidence (per 10,000 person-years) of PID was 32.4 in 1998 and 7.9 in 2017. CONCLUSION: There was no excess risk of composite CVD or its subtypes among women with history of PID compared to matched controls. Findings from our study suggest that history of PID was associated with an increased risk of hypertension and type 2 diabetes mellitus, two major risk factors for CVD. Additional studies are required to support these findings.

Barriers and facilitators of people living with HIV receiving optimal care for hypertension and diabetes in Tanzania: a qualitative study with healthcare professionals and people living with HIV.

BACKGROUND: People living with HIV (PLWH) are at a higher risk for developing diabetes and hypertension. Often services are separate for HIV and non-communicable diseases (NCDs), but how this impacts NCD care among PLWH is unknown. We aimed to understand the barriers and facilitators for prevention, early diagnosis and safe effective care for diabetes and hypertension among PLWH. METHODS: Semi-structured interviews (SSIs) were conducted with 10 healthcare professionals (HCPs) that care for PLWH, 10 HCPs that care for people with diabetes and hypertension and 16 PLWH with a comorbidity of diabetes and/or hypertension. Participants were recruited from two healthcare facilities in Dodoma, Tanzania and purposively sampled based on age and sex. Interviews were conducted in Swahili using pre-developed topic guides, audio recorded then translated verbatim into English. An inductive thematic analysis was conducted using The Framework Method. RESULTS: Three themes were found: organisational/healthcare system factors, individual factors and syndemic factors. Organisational/healthcare system factors comprised the only facilitators for prevention (education on lifestyle behaviours and counselling on adherence), but included the most barriers overall: fragmented services, no protocol for NCD screening and lack of access to diagnostic equipment were barriers for early diagnosis whereas the former plus lack of continuity of NCD care were barriers for safe effective care. Individual factors comprised four sub-themes, three of which were considered facilitators: HCPs' knowledge of NCDs for early diagnosis, self-monitoring of NCDs for safe effective care and HCPs' personal practice for both early diagnosis and safe effective care. HCPs' knowledge was simultaneously a barrier for prevention and PLWH knowledge was a barrier for prevention and safe effective care. Syndemic factors comprised three sub-themes; all were barriers for prevention, early diagnosis and/or safe effective care: poverty and mental health of PLWH and HIV stigma. CONCLUSIONS: Organisational/healthcare system, individual and syndemic factors were found to be interlinked with barriers and facilitators that contribute to the prevention, early diagnosis and safe effective care of diabetes and hypertension among PLWH in Tanzania; these findings can inform future initiatives for making small and large health system changes to improve the health of aging PLWH.

Carbon monoxide levels in households using coal-briquette fuelled stoves exceed WHO air quality guidelines in Ulaanbaatar, Mongolia.

In 2019, a domestic raw coal ban (RCB) was introduced in Ulaanbaatar, Mongolia. Coal-briquettes have since been promoted in Ger district households, however implications for carbon monoxide (CO) exposure remains uncertain. We obtained 48-hour indoor CO concentrations in 23 Ger district households and compared these to 10 raw-coal households. Information on household characteristics, fuel use behaviour and stove venting practices was collected by survey. Mean 48-hour CO concentrations in coal-briquette households was 6.1 ppm (range 1.5-35.8 ppm) with no signfiicant differences by household, stove or venting factors. Peak time-weighted average CO concentrations exceeded WHO Indoor Air Quality guidelines in 9 (39%) households; with all surpassing the 8-hour guideline (>8.6 ppm); 3(13%) the 24-hour guideline (>6 ppm) and 2(9%) the 1-hour guideline (>30 ppm). Median CO levels were significantly lower in coal-briquette compared to raw coal households (p = 0.049). Indoor CO reduction was associated with RCB implementation although hazardous levels persist in this setting.

The impact of COVID-19 public health restrictions on particulate matter pollution measured by a validated low-cost sensor network in Oxford, UK.

Emergency responses to the COVID-19 pandemic led to major changes in travel behaviours and economic activities with arising impacts upon urban air quality. To date, these air quality changes associated with lockdown measures have typically been assessed using limited city-level regulatory monitoring data, however, low-cost air quality sensors provide capabilities to assess changes across multiple locations at higher spatial-temporal resolution, thereby generating insights relevant for future air quality interventions. The aim of this study was to utilise high-spatial resolution air quality information utilising data arising from a validated (using a random forest field calibration) network of 15 low-cost air quality sensors within Oxford, UK to monitor the impacts of multiple COVID-19 public heath restrictions upon particulate matter concentrations (PM10, PM2.5) from January 2020 to September 2021. Measurements of PM10 and PM2.5 particle size fractions both within and between site locations are compared to a pre-pandemic related public health restrictions baseline. While average peak concentrations of PM10 and PM2.5 were reduced by 9-10 µg/m3 below typical peak levels experienced in recent years, mean daily PM10 and PM2.5 concentrations were only ∼1 µg/m3 lower and there was marked temporal (as restrictions were added and removed) and spatial variability (across the 15-sensor network) in these observations. Across the 15-sensor network we observed a small local impact from traffic related emission sources upon particle concentrations near traffic-oriented sensors with higher average and peak concentrations as well as greater dynamic range, compared to more intermediate and background orientated sensor locations. The greater dynamic range in concentrations is indicative of exposure to more variable emission sources, such as road transport emissions. Our findings highlight the great potential for low-cost sensor technology to identify highly localised changes in pollutant concentrations as a consequence of changes in behaviour (in this case influenced by COVID-19 restrictions), generating insights into non-traffic contributions to PM emissions in this setting. It is evident that additional non-traffic related measures would be required in Oxford to reduce the PM10 and PM2.5 levels to within WHO health-based guidelines and to achieve compliance with PM2.5 targets developed under the Environment Act 2021.

Incidence of Cardiometabolic Diseases in People With and Without Human Immunodeficiency Virus in the United Kingdom: A Population-Based Matched Cohort Study.

BACKGROUND: Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with human immunodeficiency virus (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events, and common risk factors. METHODS: This was a nationwide, population-based, cohort study comparing adult (≥18 years old) PWH with people without human immunodeficiency virus (HIV) matched on age, sex, ethnicity, and location. The primary outcome was composite CVD comprising stroke, myocardial infarction, peripheral vascular disease, ischemic heart disease, and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD), and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome. RESULTS: We identified 9233 PWH and matched them with 35 721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR], 1.50; 95% confidence interval [CI], 1.28-1.77), stroke (aHR, 1.42; 95% CI, 1.08-1.86), ischemic heart disease (aHR, 1.55; 95% CI, 1.24-1.94), hypertension (aHR, 1.37; 95% CI, 1.23-1.53), type 2 diabetes (aHR, 1.28; 95% CI, 1.09-1.50), CKD (aHR, 2.42; 95% CI, 1.98-2.94), and all-cause mortality (aHR, 2.84; 95% CI, 2.48-3.25). CONCLUSIONS: PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.

Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study.

RATIONALE & OBJECTIVE: Metabolically healthy obesity (obesity without any metabolic abnormality) is not considered to be associated with increased risk of morbidity and mortality. We examined and quantified the association between metabolically healthy overweight/obesity and the risk of incident chronic kidney disease (CKD) in a British primary care population. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: 4,447,955 of the 5,182,908 adults in The Health Improvement Network (THIN) database (United Kingdom, 1995-2015) with a recorded body mass index (BMI) at the time of registration date who were free of CKD and cardiovascular disease. EXPOSURE: 11 body size phenotypes were created, defined by BMI categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and dyslipidemia). OUTCOME: Incident CKD defined as a recorded code for kidney replacement therapy, a recorded diagnosis of CKD, or by an estimated glomerular filtration rate of<60mL/min/1.73m2 for≥90 days, or a urinary albumin-creatinine ratio>3mg/mmol for≥90 days. RESULTS: Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) had metabolically healthy overweight and metabolically healthy obesity, respectively. During a mean follow-up interval of 5.4±4.3 (SD) years, compared with individuals with a metabolically healthy normal weight (n=1,656,231), there was a higher risk of incident CKD among those who had metabolically healthy overweight (adjusted HR, 1.30 [95% CI, 1.28-1.33]) and metabolically healthy obesity (adjusted HR, 1.66 [95% CI, 1.62-1.70]). The association was stronger in those younger than 65 years of age. In all BMI categories, there was greater risk of incident CKD with a greater number of metabolic abnormalities in a graded manner. LIMITATIONS: Potential misclassification of metabolic status due to delayed diagnosis and residual confounding due to unmeasured factors. CONCLUSIONS: Overweight and obesity without metabolic abnormality are associated with a higher risk of incident CKD compared with those with normal body weight and no metabolic abnormality.

Association of alcohol drinking with incident type 2 diabetes and pre-diabetes: The Guangzhou Biobank Cohort Study.

AIMS: We examined associations of baseline alcohol drinking with incident type 2 diabetes (T2D) or impaired fasting glucose (IFG), and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B). MATERIALS AND METHODS: All participants were aged 50+ (mean = 60.45; standard deviation = 6.88) years. Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident T2D was defined as fasting glucose ≥7.0 mmol/L or post-load glucose ≥11.1 mmol/L at follow-up examination (2008-2012), self-reported T2D and/or initiation of hypoglycaemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/L and <7 mmol/L. RESULTS: Of 15,716 participants without diabetes and 11,232 participants without diabetes and IFG at baseline, 1624 (10.33%) developed incident T2D and 1004 (8.94%) developed incident IFG during an average 4 years of follow-up. After multivariable adjustments, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident hyperglycaemia (T2D + IFG) (odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.95-1.27, and 0.90 (0.69-1.18), respectively), whereas heavy alcohol drinking was associated with a higher risk of incident hyperglycaemia (T2D + IFG) (OR = 1.82, 95% CI 1.24-2.68). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B/ALDH2 genes with alcohol drinking on incident T2D and/or IFG were found (P for interaction from 0.12 to 0.85). CONCLUSIONS: Our results support a detrimental effect of heavy alcohol use on IFG and T2D. No protective effect was found for those carrying lower risk alleles for ADH1B/ALDH2 genes.

Cooking outdoors or with cleaner fuels does not increase malarial risk in children under 5 years: a cross-sectional study of 17 sub-Saharan African countries.

BACKGROUND: Smoke from solid biomass cooking is often stated to reduce household mosquito levels and, therefore, malarial transmission. However, household air pollution (HAP) from solid biomass cooking is estimated to be responsible for 1.67 times more deaths in children aged under 5 years compared to malaria globally. This cross-sectional study investigates the association between malaria and (i) cleaner fuel usage; (ii) wood compared to charcoal fuel; and, (iii) household cooking location, among children aged under 5 years in sub-Saharan Africa (SSA). METHODS: Population-based data was obtained from Demographic and Health Surveys (DHS) for 85,263 children within 17 malaria-endemic sub-Saharan countries who were who were tested for malaria with a malarial rapid diagnostic test (RDT) or microscopy. To assess the independent association between malarial diagnosis (positive, negative), fuel type and cooking location (outdoor, indoor, attached to house), multivariable logistic regression was used, controlling for individual, household and contextual confounding factors. RESULTS: Household use of solid biomass fuels and kerosene cooking fuels was associated with a 57% increase in the odds ratio of malarial infection after adjusting for confounding factors (RDT adjusted odds ratio (AOR):1.57 [1.30-1.91]; Microscopy AOR: 1.58 [1.23-2.04]) compared to cooking with cleaner fuels. A similar effect was observed when comparing wood to charcoal among solid biomass fuel users (RDT AOR: 1.77 [1.54-2.04]; Microscopy AOR: 1.21 [1.08-1.37]). Cooking in a separate building was associated with a 26% reduction in the odds of malarial infection (RDT AOR: 0.74 [0.66-0.83]; Microscopy AOR: 0.75 [0.67-0.84]) compared to indoor cooking; however no association was observed with outdoor cooking. Similar effects were observed within a sub-analysis of malarial mesoendemic areas only. CONCLUSION: Cleaner fuels and outdoor cooking practices associated with reduced smoke exposure were not observed to have an adverse effect upon malarial infection among children under 5 years in SSA. Further mixed-methods research will be required to further strengthen the evidence base concerning this risk paradigm and to support appropriate public health messaging in this context.

Health care professionals' perceptions about atrial fibrillation care in the Brazilian public primary care system: a mixed-methods study.

BACKGROUND: Atrial fibrillation (AF) negatively impacts health systems worldwide. We aimed to capture perceptions of and barriers and facilitators for AF care in Brazilian primary care units (PCUs) from the perspective of healthcare professionals (HCPs). METHODS: This mixed-methods, cross-sectional study utilised an exploratory sequential design, beginning with the quantitative data collection (up to 18 closed questions) immediately followed by a semi-structured interview. HCPs were recruited from 11 PCUs in the Sao Paulo region and included managers, physicians, pharmacists, nurses and community health agents. Descriptive statistics were used to present findings from the quantitative questionnaire and inductive analysis was used to identify themes from the qualitative data. RESULTS: One hundred seven HCPs were interviewed between September 2019 and May 2020. Three main themes were identified that encapsulated barriers and facilitators to AF care: access to care (appointments, equipment/tests and medication), HCP and patient roles (HCP/patient relationship and patient adherence) and the role of the organisation/system (infrastructure, training and protocols/guidelines). Findings from the qualitative analysis reinforced the quantitative findings, including a lack of AF-specific training for HCPs, protocols/guidelines on AF management, INR tests in the PCUs, patient knowledge of AF management and novel oral anticoagulants (NOACs) as key barriers to optimal AF care. CONCLUSIONS: Development and implementation of AF-specific training for PCU HCPs are needed in Brazil, along with evidence-based protocols and guidelines, educational programmes for patients, better access to INR tests for patients taking warfarin and availability of NOACs.

Effectiveness of interventions to reduce household air pollution from solid biomass fuels and improve maternal and child health outcomes in low- and middle-income countries: A systematic review and meta-analysis.

Interventions to reduce household air pollution (HAP) are key to reducing associated morbidity and mortality in low- and middle- income countries (LMICs); especially among pregnant women and young children. This systematic review aims to determine the effectiveness of interventions aimed to reduce HAP exposure associated with domestic solid biomass fuel combustion, compared to usual cooking practices, for improving health outcomes in pregnant women and children under five in LMIC settings. A systematic review and meta-analysis was undertaken with searches undertaken in MEDLINE, EMBASE, CENTRAL, GIM, ClinicalTrials.gov, and Greenfile in August 2020. Inclusion criteria were experimental, non-experimental, or quasi-experimental studies investigating the impact of interventions to reduce HAP exposure and improve associated health outcomes among pregnant women or children under 5 years. Study selection, data extraction, and quality assessment using the Effective Public Health Practice Project tool were undertaken independently by two reviewers. Seventeen out of 7293 retrieved articles (seven pregnancy, nine child health outcome; 13 studies) met the inclusion criteria. These assessed improved cookstoves (ICS; n = 10 studies), ethanol stoves (n = 1 study), and Liquefied Petroleum Gas (LPG; n = 2 studies) stoves interventions. Meta-analysis showed no significant effect of ICS interventions compared to traditional cooking for risk of preterm birth (n = 2 studies), small for gestational age (n = 2 studies), and incidence of acute respiratory infections (n = 6 studies). Although an observed increase in mean birthweight was observed, this was not statistically significant (n = 4). However, ICS interventions reduced the incidence of childhood burns (n = 3; observations = 41 723; Rate Ratio: 0.66 [95% CI: 0.45-0.96]; I2 : 46.7%) and risk of low birth weight (LBW; n = 4; observations = 3456; Odds Ratio: 0.73 [95% CI: 0.61-0.87]; I2 : 21.1%). Although few studies reported health outcomes, the data indicate that ICS interventions were associated with reduced risk of childhood burns and LBW. The data highlight the need for the development and implementation of robust, well-reported and monitored, community-driven intervention trials with longer-term participant follow-up.

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.

Decreased renal function is associated with incident dementia: An IMRD-THIN retrospective cohort study in the UK.

INTRODUCTION: Decreased renal function is a potential risk factor for dementia. METHODS: This retrospective cohort study of 2.8 million adults aged ≥50 years used the IMRD-THIN database, representative of UK primary care, from January 1, 1995 to February 24, 2020. The associations between estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) with incident all-cause dementia were analyzed using Cox regression. RESULTS: In the eGFR cohort (n = 2,797,384), worsening renal dysfunction was associated with increased hazard of all-cause dementia, with greatest hazard at eGFR 15-30 ml/min/1.73min2 (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19-1.33). In the ACR cohort (n = 641,912), the hazard of dementia increased from ACR 3-30 mg/mmol (HR 1.13, 95% CI 1.10-1.15) to ACR > 30 mg/mmol (HR 1.25, 95% CI 1.18-1.33). DISCUSSION: Worsening eGFR and albuminuria have graded associations with the risk of dementia, which may have significant implications for the care of patients with kidney disease.

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

BACKGROUND AND PURPOSE: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. METHODS: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. RESULTS: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). CONCLUSIONS: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. METHODS: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. RESULTS: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence. CONCLUSIONS: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.