Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study.

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

Self-reported changes in alcohol and tobacco use during COVID-19: findings from the eastern part of WHO European Region.

BACKGROUND: The COVID-19 pandemic might impact substance use behaviours around the globe. In this study, we investigate changes in alcohol and tobacco use in the second half of 2020 in countries of the eastern part of the WHO European Region. METHODS: Self-reported changes in alcohol and tobacco use among 11 295 adults from 18 countries in the eastern part of the WHO European Region were collected between August 2020 and January 2021. The non-probabilistic sample was weighted for age, gender and education. For each country, proportions of respondents reporting a decrease, no change or increase in substance use over the past 3 months were examined, and multinomial regression models were used to test associations with age, gender and past-year alcohol use. RESULTS: In most countries, about half of the respondents indicating past-year alcohol or tobacco use reported no change in their substance use. Of those alcohol users who reported changes in their alcohol use, a larger proportion reported a decrease than an increase in most countries. The opposite was true for tobacco use. Women, young adults and past-year harmful alcohol users were identified as being more likely to change their substance use behaviour. CONCLUSION: We found diverging overall trends for alcohol and tobacco use in the second half of 2020. The patterns of change vary according to age, gender and past-year substance use. Individuals at risk to increase their substance use during the COVID-19 pandemic require most policy considerations.

Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

BACKGROUND: Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies. METHODS: In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death. FINDINGS: From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease. INTERPRETATION: Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Regional differences in cardiovascular mortality in Kazakhstan: further evidence for the 'Russian mortality paradox'?

BACKGROUND: The role of alcohol consumption in patterns of CVD mortality in Central Asia is still largely unexplored. Previous research in Kazakhstan and Kyrgyzstan has found that ethnic Russians have higher adult mortality rates than native ethnic groups, despite their higher socio-economic status. This has been termed the 'Russian mortality paradox'. METHODS: We calculated age-standardized CVD mortality data by gender and region of Kazakhstan, based on mortality data obtained from the Ministry of Health and population data from the State Agency for Statistics. We analysed data on self-reported alcohol consumption from the nationally representative 5th National Behavior Study. RESULTS: We found substantial differences in CVD mortality rates across regions, as well as between males and females. With the exception of Almaty and Astana cities, mortality rates are highest in the country's North-Eastern regions and lowest in South-Western regions, despite the fact that North-Eastern regions have higher income levels. Patterns of self-reported alcohol consumption and alcohol sales follow a similar pattern. One explanation could be related to higher self-reported drinking prevalence among ethnic Russians who live predominantly in the country's North-Eastern regions. CONCLUSIONS: Hazardous alcohol consumption seems to be highest in Kazakhstan's North-Eastern regions, which might be related to different patterns of alcohol consumption among different ethnic groups. However, more detailed analyses are required to corroborate these assumptions. The high overall rates suggest the need for population-based measures, such as increasing taxes on alcohol, in particular spirits such as vodka, and strengthening the capacity of primary health care.

Assessment of hypercholesterolemia prevalence and its demographic variations in the Republic of Kazakhstan.

Hypercholesterolemia is a major risk factor for cardiovascular disease, the leading cause of death in Kazakhstan. Understanding its prevalence is vital for effective public health planning and interventions. This study aimed to assess the scale of hypercholesterolemia in the Republic of Kazakhstan and to identify differences among distinct population groups. A cross-sectional study involving 6720 participants (a nationally representative survey.) aged 18-69 was conducted from October 2021 to May 2022 across all 17 regions of Kazakhstan. The magnitude of hypercholesterolemia was 43.5%. Cholesterol levels were determined through blood biochemical analysis. Age, sex, geographic location, and ethnicity served as covariates. The majority of participants (65.49%) were from urban areas with an almost equal gender distribution (50.07% male and 49.93% female). The predominant age groups were 18-29 years (25.71%) and 30-39 years (25.12%), and 65.09% identified as Kazakh. The prevalence increased with age, with the 60-69 age group showing the highest rate at 71.14%. Women had slightly higher rates than men. Geographical differences were evident, with regions like Astana city and Almaty region showing significant disparities. Kazakhs had a lower rate compared to other ethnicities. Age, region, and BMI were significant predictors for hypercholesterolemia in both binary and multivariate logistic regression analyses. The study revealed a significant prevalence of hypercholesterolemia in Kazakhstan, with increasing age as a major determinant. Women, especially those over 50, and certain regions showed higher cholesterol levels. The disparities observed across regions and ethnicities suggest the need for targeted public health interventions to address this pressing health concern.

Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

BACKGROUND: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. METHODS: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. RESULTS: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). CONCLUSIONS: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Exploring HPV vaccine knowledge, attitudes, barriers and information sources among parents, health professionals and teachers in Kazakhstan: a mixed-methods study protocol.

INTRODUCTION: Human papillomavirus (HPV) is a prevalent sexually transmitted infection linked to certain types of malignant neoplasms, notably cervical cancer (CC). In Kazakhstan, a high prevalence of high oncogenic HPV types (HR-HPV) has been observed, and CC ranks as the second most common malignancy among women with a crude incidence rate of 18.3 cases per 100 000 women. The HPV vaccine, developed as the primary prevention measure against HPV infection, including the most prevalent HR-HPV, received approval from the WHO in 2009. In 2014, Kazakhstan initiated HPV vaccination as a pilot project in four sub-national regions; however, it was later in 2017 discontinued due to widespread parental refusal influenced by negative media reports. This study aims to examine knowledge, attitudes, information sources, barriers to HPV vaccination and factors associated with HPV vaccination hesitancy among different target groups in Kazakhstan prior to the HPV vaccine re-launch announced by the Ministry of Health. METHODS AND ANALYSIS: This mixed-method-designed research comprises quantitative and qualitative components. Data on HPV awareness, attitudes towards HPV vaccination and sources of information will be collected through an online survey administered by parents and legal guardians, health professionals, and schoolteachers in the Republic of Kazakhstan between January 2023 and January 2024. Additionally, qualitative data on Kazakhstani parental beliefs and attitudes toward HPV vaccination will be collected through online focus group discussions. ETHICS AND DISSEMINATION OF RESULTS: The study has been approved by the local ethics committee at the Kazakhstan Medical University "Higher School of Public Health" (KMU "KSPH") (No. 138 of 31.05.2021). The results will be reported in publications, at conferences among researchers and healthcare and school education professionals in Kazakhstan, and internationally.

Post-conflict acute stress reactions in Kazakhstan in the aftermath of January 2022 unrests: A national survey.

Background: In January 2022 Kazakhstan experienced unprecedented nationwide protests that quickly turned to violent riots. Although the number of individuals affected physically by the disturbances were cited, the emotional toll of the events remains undetermined. The aim of this study was to evaluate the comparative rates of acute stress reactions in Kazakhstan in the aftermath of the unrests. Methods: A cross-sectional, population-based online survey was conducted one month after the start of the disturbances. The study questionnaire were completed anonymously and included the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) and the General Anxiety Disorder-7 (GAD-7), as well as socio-demographic and event exposure information. Results: Of the 7021 people who initially agreed to participate, 6510 were able to complete the full survey. For a cut-off of ≥3 on the PC-PTSD-5, 14.8 % of the study participants exhibited symptoms. With a cut-off of ≥4, this percentage reduced to 4.6 %. Participants from Almaty city and Almaty region who experienced the most extensive disturbances showed a doubled prevalence compared to the national level (30.0 % for a cut-off of ≥3, and 10.1 % for a cut-off of ≥4). At the national level, the prevalence of anxiety symptoms, defined as a score of ≥10 on the GAD-7, stood at 10.9 %. This prevalence decreased to 4.2 % when considering a cut-off of ≥15. Conclusion: Health authorities of riot-affected areas ought to be aware of the population level mental health impact of the civil conflict and consider provision of targeted interventions to mitigate the long-term consequence of these lifespan disorders, while also seeking for the peaceful resolution of the ensuing conflicts.

The Burden of Disease due to COVID-19 (BoCO-19): A study protocol for a secondary analysis of surveillance data in Southern and Eastern Europe, and Central Asia.

INTRODUCTION: The COVID-19 pandemic has had an extensive impact on public health worldwide. However, in many countries burden of disease indicators for COVID-19 have not yet been calculated or used for monitoring. The present study protocol describes an approach developed in the project "The Burden of Disease due to COVID-19. Towards a harmonization of population health metrics for the surveillance of dynamic outbreaks" (BoCO-19). The process of data collection and aggregation across 14 different countries and sub-national regions in Southern and Eastern Europe and Central Asia is described, as well as the methodological approaches used. MATERIALS AND METHODS: The study implemented in BoCO-19 is a secondary data analysis, using information from national surveillance systems as part of mandatory reporting on notifiable diseases. A customized data collection template is used to gather aggregated data on population size as well as COVID-19 cases and deaths. Years of life lost (YLL), as one component of the number of Disability Adjusted Life Years (DALY), are calculated as described in a recently proposed COVID-19 disease model (the 'Burden-EU' model) for the calculation of DALY. All-cause mortality data are collected for excess mortality sensitivity analyses. For the calculation of Years lived with disability (YLD), the Burden-EU model is adapted based on recent evidence. Because Covid-19 cases vary in terms of disease severity, the possibility and suitability of applying a uniform severity distribution of cases across all countries and sub-national regions will be explored. An approach recently developed for the Global Burden of Disease Study, that considers post-acute consequences of COVID-19, is likely to be adopted. Findings will be compared to explore the quality and usability of the existing data, to identify trends across age-groups and sexes and to formulate recommendations concerning potential improvements in data availability and quality. DISCUSSION: BoCO-19 serves as a collaborative platform in order to build international capacity for the calculation of burden of disease indicators, and to support national experts in the analysis and interpretation of country-specific data, including their strengths and weaknesses. Challenges include inherent differences in data collection and reporting systems between countries, as well as assumptions that have to be made during the calculation process.

Circulating adiponectin levels, expression of adiponectin receptors, and methylation of adiponectin gene promoter in relation to Alzheimer's disease.

BACKGROUND: The role of adiponectin (ADIPOQ) in Alzheimer's disease (AD) has been documented, however, demonstrating controversial results. In this study, we investigated blood serum ADIPOQ levels, methylation of the adiponectin gene promoter, and adiponectin receptors (AdipoR1 and AdipoR2) expression in blood samples isolated from AD patients and healthy controls. METHODS: We performed a case-control study including 248 subjects (98 AD patients and 150 healthy controls); ADIPOQ serum levels, AdipoR1, and AdipoR2 levels in PBMC were measured by ELISA Kits, and ADIPOQ gene methylation was analyzed using methyl-specific PCR. RESULTS: Serum adiponectin levels were threefold higher in the AD group compared to the controls. We have also found a positive correlation between adiponectin and MMSE scores and high-density lipoprotein cholesterol (HDL-C) in AD patients. A significant difference in the proportion of methylation of the CpG sites at - 74 nt of the ADIPOQ gene promoter was detected in AD cases, and the levels of adiponectin in blood serum were significantly higher in methylated samples in the AD group compared to controls. The amount of AdipoR1 was significantly higher among AD subjects, while the expression of AdipoR2 did not vary between AD patients and controls. CONCLUSION: These findings may contribute to a deeper understanding of the etiological factors leading to the development of dementia and may serve as a basis for the development of predictive biomarkers of AD.

Neuropsychological Assessment of Community-Dwelling Older Adults in Almaty, Kazakhstan.

Cognitive impairment in older adults is a major public concern for Kazakhstan's aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.

Alcohol control policies in Former Soviet Union countries: A narrative review of three decades of policy changes and their apparent effects.

ISSUES: The last Soviet anti-alcohol campaign of 1985 resulted in considerably reduced alcohol consumption and saved thousands of lives. But once the campaign's policies were abandoned and the Soviet alcohol monopoly broken up, a steep rise in mortality was observed in many of the newly formed successor countries, although some kept their monopolies. Almost 30 years after the campaign's end, the region faces diverse challenges in relation to alcohol. APPROACH: The present narrative review sheds light on recent drinking trends and alcohol policy developments in the 15 Former Soviet Union (FSU) countries, highlighting the most important setbacks, achievements and best practices. Vignettes of alcohol control policies in Belarus, Estonia, Kazakhstan, Lithuania and Uzbekistan are presented to illustrate the recent developments. KEY FINDINGS: Over the past decade, drinking levels have declined in almost all FSU countries, paralleled by the introduction of various alcohol-control measures. The so-called three 'best buys' put forward by the World Health Organization to reduce alcohol-attributable burden (taxation and other measures to increase price, restrictions on alcohol availability and marketing) are relatively well implemented across the countries. IMPLICATIONS: In recent years, evidence-based alcohol policies have been actively implemented as a response to the enormous alcohol-attributable burden in many of the countries, although there is big variance across and within different jurisdictions. CONCLUSION: Strong declines in alcohol consumption were observed in the 15 FSU countries, which have introduced various alcohol control measures in recent years, resulting in a reduction of alcohol consumption in the World Health Organization European region overall.

Burden of Ischemic Heart Disease in Central Asian Countries, 1990-2017.

BACKGROUND: The burden of ischemic heart disease (IHD) is high. There is limited information on the burden of IHD in identified high risk areas like Central Asia (CA) which is comprised of Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Turkmenistan, Mongolia, Uzbekistan and Tajikistan. This study addresses the burden of IHD in CA at the regional and country levels. METHODS: Using data from the latest iteration of the Global Burden of Disease Study (GBD), this study provides age-adjusted mortality, prevalence, and Disability Adjusted Life Years (DALYs) of IHD by sex in the CA region, and national levels for countries in this region from 1990 to 2017. RESULTS: The CA region has a higher IHD burden than the rest of the world over the studied period. Amongst the countries within this region, age-standardized mortality and DALY rates in Uzbekistan are the highest not only in CA but worldwide, while Armenia consistently has the lowest IHD burden in CA. Unhealthy diet, high systolic blood pressure and LDL-cholesterol are the risk factors with the highest attributable IHD DALYs. CONCLUSION: Increasing burden of IHD over time in CA can be partially explained by the economic crisis in the 1990s. There is considerable variation in IHD DALY rates among countries in the CA region. The reasons for such differences are likely multifactorial such as differences in risk factors distribution, health care effectiveness, political, social and economic factors.

Primary prevention efforts are poorly developed in people at high cardiovascular risk: A report from the European Society of Cardiology EURObservational Research Programme EUROASPIRE V survey in 16 European countries.

BACKGROUND: European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational Research Programme in 2016-2018. The main objective was to determine whether the 2016 Joint European Societies' guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been implemented in clinical practice. METHODS: The method used was a cross-stional survey in 78 centres from 16 European countries. Patients without a history of atherosclerotic cardiovascular disease either started on blood pressure and/or lipid and/or glucose lowering treatments were identified and interviewed ≥ 6 months after the start of medication. RESULTS: A total of 3562 medical records were reviewed and 2759 patients (57.6% women; mean age 59.0 ± 11.6 years) interviewed (interview rate 70.0%). The risk factor control was poor with 18.1% of patients being smokers, 43.5% obese (body mass index ≥30 kg/m2) and 63.8% centrally obese (waist circumference ≥88 cm for women, ≥102 cm for men). Of patients on blood pressure lowering medication 47.0% reached the target of <140/90 mm Hg (<140/85 mm Hg in people with diabetes). Among treated dyslipidaemic patients only 46.9% attained low density lipoprotein-cholesterol target of <2.6 mmol/l. Among people treated for type 2 diabetes mellitus, 65.2% achieved the HbA1c target of <7.0%. CONCLUSION: The primary care arm of the EUROASPIRE V survey revealed that large proportions of people at high cardiovascular disease risk have unhealthy lifestyles and inadequate control of blood pressure, lipids and diabetes. Thus, the potential to reduce the risk of future cardiovascular disease throughout Europe by improved preventive cardiology programmes is substantial.