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Fulltext Constructing causal pathways for premature cardiovascular disease mortality using directed acyclic graphs with integrating evidence synthesis and expert knowledge

Hasani WSR, Musa KI, Chen XW, Cheng KY

Sci Rep, 2024 Nov 21;14(1):28849.
PMID: 39572630 DOI: 10.1038/s41598-024-80091-0

Cardiovascular disease (CVD) is a major global cause of premature mortality. While multiple studies propose CVD mortality prediction models based on regression frameworks, incorporating causal understanding through causal inference approaches can enhance accuracy. This paper demonstrates a methodology combining evidence synthesis and expert knowledge to construct a causal model for premature CVD mortality using Directed Acyclic Graphs (DAGs). The process involves three phases: (1) initial DAG development based on the Evidence Synthesis for Constructing Directed Acyclic Graphs (ESC-DAGs) framework, (2) validation and consensus-building with 12 experts using the Fuzzy Delphi method (FDM), and (3) application to data analysis using population-based survey data linked with death records. Expert input refined the initial DAG model, achieving consensus on 45 causal paths. The revised model guided selection of confounding variables for adjustment. For example, to estimate the total effect of diabetes on premature CVD mortality, the suggested adjustment set included age, dietary pattern, genetic/family history, sex hormones, and physical activity. Testing different DAG models showed agreement between expert ratings and data accuracy from regression models. This systematic approach contributes to DAG methodology, offering a transparent process for constructing causal pathways for premature CVD mortality.

Matched MeSH terms: Mortality, Premature*
Gone Too Soon: priorities for action to prevent premature mortality associated with mental illness and mental distress

O'Connor RC, Worthman CM, Abanga M, Athanassopoulou N, Boyce N, Chan LF, et al.

Lancet Psychiatry, 2023 Jun;10(6):452-464.
PMID: 37182526 DOI: 10.1016/S2215-0366(23)00058-5

Globally, too many people die prematurely from suicide and the physical comorbidities associated with mental illness and mental distress. The purpose of this Review is to mobilise the translation of evidence into prioritised actions that reduce this inequity. The mental health research charity, MQ Mental Health Research, convened an international panel that used roadmapping methods and review evidence to identify key factors, mechanisms, and solutions for premature mortality across the social-ecological system. We identified 12 key overarching risk factors and mechanisms, with more commonalities than differences across the suicide and physical comorbidities domains. We also identified 18 actionable solutions across three organising principles: the integration of mental and physical health care; the prioritisation of prevention while strengthening treatment; and the optimisation of intervention synergies across social-ecological levels and the intervention cycle. These solutions included accessible, integrated high-quality primary care; early life, workplace, and community-based interventions co-designed by the people they should serve; decriminalisation of suicide and restriction of access to lethal means; stigma reduction; reduction of income, gender, and racial inequality; and increased investment. The time to act is now, to rebuild health-care systems, leverage changes in funding landscapes, and address the effects of stigma, discrimination, marginalisation, gender violence, and victimisation.

Matched MeSH terms: Mortality, Premature
Fulltext Dietary fatty acids and edible fruit oil: Potential therapy for heart

Noor Atiqah Aizan Abd Kadir, Azrina Azlan

The Pertanika Journal of Scholarly Research Reviews, 2017;3(2):45-55.
MyJurnal

Cardiovascular disease (CVD) is a major cause of disability and premature death throughout the world. This disease is commonly experienced by people with unhealthy lifestyle, stress and physical inactivity. Cholesterol has received the most attention as single risk factor of CVD. Reducing the intake of cholesterol, saturated fat, and trans faty acids may be beneficial, yet controversy is still lingering to what constituents more beneficial dietary fats. The purpose of this article is to give an overview on the impact of major dietary fatty acids on cardiovascular morbidity and mortality and to give an insightful information regarding fatty acids composition in selected fruits oils in search for novel oils as potential therapy against CVD.

Matched MeSH terms: Mortality, Premature
Fulltext Burden of disease attributable to overweight and obesity in Malaysia

Foo, Lee Peng, Hanny Zurina Hamzah, Norashidah Mohamed Nor, Rusmawati Said

Malaysian Journal of Public Health Medicine, 2018;18(1):0-0.
MyJurnal

The overweight and obese population may affect the population health which can lead to economic stability and development of the countries to be compromised. Thus, this study estimates the burden of disease attributable to overweight and obesity in Malaysia for adults aged 20-59 years old. Population attribution fraction (PAF) and disability-adjusted life year (DALY) have been used to quantify years of life lost from premature death and number of years lost due to disability resulting from obesity and overweight. The burden of disease attributable to overweight was 1582 and 1146 PYs per 1000 persons for male and female, respectively. Meanwhile, the burden of disease attributable to obesity was 2951 PYs per 1000 persons with women in the lead at 1657 PYs per 1000 persons. The burden of overweight and obesity among Malaysian adults is substantial. The outcome of this study is crucial as it gives a comprehensive information on the burden of overweight and obesity in Malaysia. The information from this study also enables the authorities to develop activities and programs to combat obesity and tomaintain healthy lifestyle among Malaysian.

Matched MeSH terms: Mortality, Premature
Malaysian burden of disease: years of life lost due to premature deaths

Khaw WF, Chan YM, Nasaruddin NH, Alias N, Tan L, Ganapathy SS

BMC Public Health, 2023 Jul 18;23(1):1383.
PMID: 37464344 DOI: 10.1186/s12889-023-16309-z

BACKGROUND: In Malaysia, the previous mortality burden has been a significant concern, particularly due to the high prevalence of noncommunicable diseases (NCDs) as the leading cause of death. Estimates of mortality are key indicators for monitoring population health and determining priorities in health policies and health planning. The aim of this study was to estimate the disease burden attributed to 113 major diseases and injuries in Malaysia in 2018 using years of life lost (YLL) method.
METHODS: This study included all deaths that occurred in Malaysia in 2018. The YLL was derived by adding the number of deaths from 113 specific diseases and multiplying it by the remaining life expectancy for that age and sex group. Data on life expectancy and mortality were collected from the Department of Statistics Malaysia.
RESULTS: In 2018, there were 3.5 million YLL in Malaysia. Group II (NCDs) caused 72.2% of total YLL. Ischaemic heart disease was the leading cause of premature mortality among Malaysians (17.7%), followed by lower respiratory infections (9.7%), road traffic injuries (8.7%), cerebrovascular disease (stroke) (8.0%), and diabetes mellitus (3.9%).
CONCLUSIONS: NCDs are a significant health concern in Malaysia and are the primary contributor to the overall burden of disease. These results are important in guiding the national health systems on how to design and implement effective interventions for NCDs, as well as how to prioritise and allocate healthcare resources. Key strategies to consider include implementing health promotion campaigns, adopting integrated care models, and implementing policy and regulatory measures. These approaches aim to enhance health outcomes and the managements of NCDs in Malaysia.

Matched MeSH terms: Mortality, Premature
Fulltext The burden of premature mortality from cardiovascular diseases: A systematic review of years of life lost

Rodzlan Hasani WS, Muhamad NA, Hanis TM, Maamor NH, Wee CX, Omar MA, et al.

PLoS One, 2023;18(4):e0283879.
PMID: 37083866 DOI: 10.1371/journal.pone.0283879

INTRODUCTION: Premature mortality refers to deaths that occur before the expected age of death in a given population. Years of life lost (YLL) is a standard parameter that is frequently used to quantify some component of an "avoidable" mortality burden.
OBJECTIVE: To identify the studies on premature cardiovascular disease (CVD) mortality and synthesise their findings on YLL based on the regional area, main CVD types, sex, and study time.
METHOD: We conducted a systematic review of published CVD mortality studies that reported YLL as an indicator for premature mortality measurement. A literature search for eligible studies was conducted in five electronic databases: PubMed, Scopus, Web of Science (WoS), and the Cochrane Central Register of Controlled Trials (CENTRAL). The Newcastle-Ottawa Scale was used to assess the quality of the included studies. The synthesis of YLL was grouped into years of potential life lost (YPLL) and standard expected years of life lost (SEYLL) using descriptive analysis. These subgroups were further divided into WHO (World Health Organization) regions, study time, CVD type, and sex to reduce the effect of heterogeneity between studies.
RESULTS: Forty studies met the inclusion criteria for this review. Of these, 17 studies reported premature CVD mortality using YPLL, and the remaining 23 studies calculated SEYLL. The selected studies represent all WHO regions except for the Eastern Mediterranean. The overall median YPLL and SEYLL rates per 100,000 population were 594.2 and 1357.0, respectively. The YPLL rate and SEYLL rate demonstrated low levels in high-income countries, including Switzerland, Belgium, Spain, Slovenia, the USA, and South Korea, and a high rate in middle-income countries (including Brazil, India, South Africa, and Serbia). Over the past three decades (1990-2022), there has been a slight increase in the YPLL rate and the SEYLL rate for overall CVD and ischemic heart disease but a slight decrease in the SEYLL rate for cerebrovascular disease. The SEYLL rate for overall CVD demonstrated a notable increase in the Western Pacific region, while the European region has experienced a decline and the American region has nearly reached a plateau. In regard to sex, the male showed a higher median YPLL rate and median SEYLL rate than the female, where the rate in males substantially increased after three decades.
CONCLUSION: Estimates from both the YPLL and SEYLL indicators indicate that premature CVD mortality continues to be a major burden for middle-income countries. The pattern of the YLL rate does not appear to have lessened over the past three decades, particularly for men. It is vitally necessary to develop and execute strategies and activities to lessen this mortality gap.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021288415.

Matched MeSH terms: Mortality, Premature
Fulltext Recent Progress of Chitosan and Chitosan Derivatives-Based Nanoparticles: Pharmaceutical Perspectives of Oral Insulin Delivery

Seyam S, Nordin NA, Alfatama M

Pharmaceuticals (Basel), 2020 Oct 14;13(10).
PMID: 33066443 DOI: 10.3390/ph13100307

Diabetes mellitus is a chronic endocrine disease, affecting more than 400 million people around the world. Patients with poorly controlled blood glucose levels are liable to suffer from life-threatening complications, such as cardiovascular, neuropathy, retinopathy and even premature death. Today, subcutaneous parenteral is still the most common route for insulin therapy. Oral insulin administration is favourable and convenient to the patients. In contrast to injection route, oral insulin delivery mimics the physiological pathway of endogenous insulin secretion. However, oral insulin has poor bioavailability (less than 2%) due to the harsh physiological environment through the gastrointestinal tract (GIT). Over the last few decades, many attempts have been made to achieve an effective oral insulin formulation with high bioavailability using insulin encapsulation into nanoparticles as advanced technology. Various natural polymers have been employed to fabricate nanoparticles as a delivery vehicle for insulin oral administration. Chitosan, a natural polymer, is extensively studied due to the attractive properties, such as biodegradability, biocompatibility, bioactivity, nontoxicity and polycationic nature. Numerous studies were conducted to evaluate chitosan and chitosan derivatives-based nanoparticles capabilities for oral insulin delivery. This review highlights strategies that have been applied in the recent five years to fabricate chitosan/chitosan derivatives-based nanoparticles for oral insulin delivery. A summary of the barriers hurdle insulin absorption rendering its low bioavailability such as physical, chemical and enzymatic barriers are highlighted with an emphasis on the most common methods of chitosan nanoparticles preparation. Nanocarriers are able to improve the absorption of insulin through GIT, deliver insulin to the blood circulation and lower blood glucose levels. In spite of some drawbacks encountered in this technology, chitosan and chitosan derivatives-based nanoparticles are greatly promising entities for oral insulin delivery.

Matched MeSH terms: Mortality, Premature
Fulltext Implementation of MPOWER approach for tobacco control in Malaysia: findings from the Global Adult Tobacco survey (GATs)

Lim Kuang Hock, Heng Pei Pei, Muhammad Fadhli Mohd Yusoff, Teh Chien Huey, Sumarni Mohamad Ghazali, Lim Hui Li, et al.

Malaysian Journal of Medicine and Health Sciences, 2020;16(1):144-154.
MyJurnal

Introduction: Tobacco induced illness remains a major contribution to premature death and global burden of dis- eases. The introduction of MPOWER policies by World Health Organization held the value to monitor the imple- mentation of the anti-smoking measures in all signatory countries. This paper aimed to investigate the application of the six MPOWER indicators among Malaysia population. Methods: We utilized the data of Global Adult Tobacco Survey-Malaysia (GATS-M) which recruited 5112 nationally representative samples of Malaysians of 15 years old and above. Descriptive statistical analysis was used to illustrate the social demographic characteristic of the respon- dents while cross tabulation was employed to describe all elements of the MPOWER indicators. Results: About one quarter (23.1%) of Malaysian adults were current tobacco users. The SHS exposure at home (38.4%) and restaurant (42.1%) were high. Approximately eight in ten (80.2%) of the smokers intended to quit, while for those attempted to quit in past one year, 9.0% utilized pharmacotherapy and 4.4% attended counseling. The awareness about tobacco related diseases was generally excellent. The overall tax make up of the cigarettes’ retail price ranging from 41.7% up to 80%. Conclusion: Tobacco consumption remains prevalent and plateau among Malaysian adults over the last two decades with substantial proportion of the population exposed to SHS. The inadequacy in the current anti-smoking policies needs urgent improvement in order to reduce the smoking norms among Malaysians population besides to achieve the ultimate goal of tobacco control end game by year 2045.

Matched MeSH terms: Mortality, Premature
Fulltext The silver lining of COVID-19: estimation of short-term health impacts due to lockdown in the Yangtze River Delta region, China

Huang L, Liu Z, Li H, Wang Y, Li Y, Zhu Y, et al.

Geohealth, 2020 Jul 07.
PMID: 32838101 DOI: 10.1029/2020GH000272

The outbreak of COVID-19 in China has led to massive lockdowns in order to reduce the spread of the epidemic and control human-to-human transmission. Subsequent reductions in various anthropogenic activities have led to improved air quality during the lockdown. In this study, we apply a widely used exposure-response function to estimate the short-term health impacts associated with PM2.5 changes over the Yangtze River Delta (YRD) region due to COVID-19 lockdown. Concentrations of PM2.5 during lockdown period reduced by 22.9% to 54.0% compared to pre-lockdown level. Estimated PM2.5-related daily premature mortality during lockdown period is 895 (95% confidential interval: 637-1081), which is 43.3% lower than pre-lockdown period and 46.5% lower compared with averages of 2017-2019. According to our calculation, total number of avoided premature death associated PM2.5 reduction during the lockdown is estimated to be 42.4 thousand over the YRD region, with Shanghai, Wenzhou, Suzhou (Jiangsu province), Nanjing, and Nantong being the top five cities with largest health benefits. Avoided premature mortality is mostly contributed by reduced death associated with stroke (16.9 thousand, accounting for 40.0%), ischemic heart disease (14.0 thousand, 33.2%) and chronic obstructive pulmonary disease (7.6 thousand, 18.0%). Our calculations do not support or advocate any idea that pandemics produce a positive note to community health. We simply present health benefits from air pollution improvement due to large emission reductions from lowered human and industrial activities. Our results show that continuous efforts to improve air quality are essential to protect public health, especially over city-clusters with dense population.

Matched MeSH terms: Mortality, Premature
Systemic Solutions for Addressing Non-Communicable Diseases in Low- and Middle-Income Countries

Ganju A, Goulart AC, Ray A, Majumdar A, Jeffers BW, Llamosa G, et al.

J Multidiscip Healthc, 2020;13:693-707.
PMID: 32801732 DOI: 10.2147/JMDH.S252300

Non-communicable diseases (NCDs) have been on the rise in low- and middle-income countries (LMICs) over the last few decades and represent a significant healthcare concern. Over 85% of "premature" deaths worldwide due to NCDs occur in the LMICs. NCDs are an economic burden on these countries, increasing their healthcare expenditure. However, targeting NCDs in LMICs is challenging due to evolving health systems and an emphasis on acute illness. The major issues include limitations with universal health coverage, regulations, funding, distribution and availability of the healthcare workforce, and availability of health data. Experts from across the health sector in LMICs formed a Think Tank to understand and examine the issues, and to offer potential opportunities that may address the rising burden of NCDs in these countries. This review presents the evidence and posits pragmatic solutions to combat NCDs.

Matched MeSH terms: Mortality, Premature
Fulltext Burden of premature mortality in Malaysia

Ummi Nadiah Yusoff, Diana Mahat, Azahadi Omar, Teh, Chien Huey, Norzawati Yoep, Riyanti Saari

Int J Public Health Res, 2013;3(1):249-258.
MyJurnal

Mortality estimates are important parameters for health monitoring and are routinely used as evidence for health policy and planning. This study aimed to estimate the mortality component of Burden of Disease in Malaysia in 2008. The 2008 mortality data from the Statistics Department were used to estimate cause-specific mortality (by age and sex) in Malaysia. Data were coded using the ICD10 (International Classification of Disease) coding. Calculation of mortality component of Burden of Disease (ie: Years of Life Lost (YLL) was done using the standard Global Burden of Disease Methodology. The total estimated deaths in Malaysia in 2008 were 124,857, of which 72,202 (57.8%) were males. The total years of life lost (YLL) for the Malaysian population in 2008 was 1.51 million in which 0.92 million (60.7%) was among males. Almost three quarter (68%) of the burden of premature deaths resulted from non-communicable diseases, followed by communicable diseases (20%) and injury (12%). Among the top three leading causes of YLL were ischaemic heart disease (17.1%), stroke (9.6%) and road traffic injuries (8.3%). In Malaysia, premature mortality mainly contributed by non-communicable diseases followed by communicable diseases and injury. A multi-agency collaboration is needed to prevent premature death and to improve quality of life.

Matched MeSH terms: Mortality, Premature
Fulltext Rejuvenating chronic disease management in Malaysian private general practice - a global perspective

Anis Safura R, Wijesinha S, Piterman L

Malays Fam Physician, 2010;5(1):49-52.
MyJurnal

Rapid epidemiological transition globally has witnessed a rising prevalence of major chronic diseases such as hypertension, diabetes, hyperlipidaemia, obesity, chronic respiratory diseases and cancers over the past 30 years. In Malaysia, these conditions are commonly managed in primary care and published evidence has consistently shown suboptimal management and poor disease control. This in turn, has led to the massive burden of treating complications in secondary care, burden to the patients and their families with regards to morbidity and premature death, and burden to the country with regards to premature loss of human capital. The crushing burden and escalating health care costs in managing chronic diseases pose a daunting challenge to our primary care system, as we remain traditionally oriented to care for acute, episodic illnesses. This paper re-examines the current evidence supporting the implementation of Wagner Chronic Care Model in primary care globally; analyses the barriers of implementation of this model in the Malaysian private general practice through SWOT (strengths, weaknesses, opportunities and threats) analysis; and discusses fundamental solutions needed to bridge the gap to achieve better outcomes.

Matched MeSH terms: Mortality, Premature
Fulltext Chronic disease management in primary care - a review of evidence

Ramli AS

Medical Health Reviews, 2008;2008(1):63-79.
MyJurnal

Primary care practice with its defining features of continuity, comprehensiveness and coordination, is the cornerstone to provide high quality community-based chronic disease management. Poor chronic disease prevention and control at the primary care level will lead to the massive burden of treating complications at secondary care, burden to the patients and their families with regards to morbidity and premature death, and burden to the country with regards to the loss of human capital. Compelling evidence showed that there are innovative and cost-effective interventions to reduce the morbidity and mortality attributable to chronic diseases, but these are rarely translated into high quality population-wide chronic disease care. Primary health care systems around the world were developed in response to acute problems and have remained so despite the increasing prevalence of chronic conditions. An evolution of primary health care system beyond the acute care model to embrace the concept of caring for long term health problems is imperative in the wake of the rising epidemic of chronic diseases. This paper aims to review the evidence supporting high quality and innovative chronic disease management models in primary care and the applicability of this approach in low and middle income countries.

Matched MeSH terms: Mortality, Premature
Assessing evidence of inequalities in access to medication for diabetic populations in low- and middle-income countries: a systematic review

Christiani Y, Dhippayom T, Chaiyakunapruk N

Glob Health Action, 2016 Dec;9(1):32505.
PMID: 28795917 DOI: 10.3402/gha.v9.32505

Background Inequalities in access to medications among people diagnosed with diabetes in low- and middle-income countries (LMICs) is a public health concern since untreated diabetes can lead to severe complications and premature death. Objective To assess evidence of inequalities in access to medication for diabetes in adult populations of people with diagnosed diabetes in LMICs. Design We conducted a systematic review of the literature using the PRISMA-Equity guidelines. A search of five databases - PubMed, Cochrane, CINAHL, PsycINFO, and EMBASE - was conducted from inception to November 2015. Using deductive content analysis, information extracted from the selected articles was analysed according to the PRISMA-Equity guidelines, based on exposure variables (place of residence, race/ethnicity, occupation, gender, religion, education, socio-economic status, social capital, and others). Results Fifteen articles (seven quantitative and eight qualitative studies) are included in this review. There were inconsistent findings between studies conducted in different countries and regions although financial and geographic barriers generally contributed to inequalities in access to diabetes medications. The poor, those with relatively low education, and people living in remote areas had less access to diabetes medications. Furthermore, we found that the level of government political commitment through primary health care and in the provision of essential medicines was an important factor in promoting access to medications. Conclusions The review indicates that inequalities exist in accessing medication among diabetic populations, although this was not evident in all LMICs. Further research is needed to assess the social determinants of health and medication access for people with diabetes in LMICs.

Matched MeSH terms: Mortality, Premature
Fulltext Measures of population health: general perspective on quality adjusted life years (QALYs) and disability adjusted life years (DALYs)

Natrah, S., Sharifa Ezat, W.P.

Malaysian Journal of Public Health Medicine, 2011;11(2):27-31.
MyJurnal

Impact of health care on the population health has been measured in terms of morbidity and mortality but this measurement doesn’t distinguish between children, adults and the elderly. It does not also take into account the losses that occur because of handicap, pain, or other disability. Therefore, measures of population health which combine information on mortality and non-fatal healthboutcomes to represent the health of a particular population as a single number was introduced. QALYs and DALYs are both common outcome measures in economic evaluations of health interventions. QALYs is the comprehensive measure of health outcome because it can simultaneously capture gains from reduced morbidity (quality gains) and reduced mortality (quantity gains) and combine these into a single measure. DALYs is primarily a measure of disease burden where it combines losses from premature death and loss of healthy life resulting from disability. Although QALYs and DALYs are almost similar in their basic concept but there are few distinct differences which must be paid attention to in order to correctly utilize these measures.

Matched MeSH terms: Mortality, Premature
A life saved at the cost of hand injury - A case of hand burn due to airbag deployment

Fadzullah NA, Kasthuri S, Basiron N

Med J Malaysia, 2019 Oct;74(5):452-453.
PMID: 31649230

According to the Malaysian Department of Statistics motor vehicle accidents are the third leading cause of death in Malaysia and accounts for 7.4% of premature deaths in 2016. With the invention of the airbag, the number of serious injuries and fatalities have been reduced significantly. However, there has also been a corresponding increase in the number of injuries attributable to these devices. The patient narrated in this case report sustained a mixed dermal thickness burn over the upper limb as a result of an airbag deployment. She recovered without other life threatening injuries.

Matched MeSH terms: Mortality, Premature
Fulltext Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015

GBD 2015 Mortality and Causes of Death Collaborators

Lancet, 2016 Oct 08;388(10053):1459-1544.
PMID: 27733281 DOI: 10.1016/S0140-6736(16)31012-1

BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.
METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).
FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.
INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
FUNDING: Bill & Melinda Gates Foundation.
Malaysian collaborators: Southern University College, Skudai, Malaysia (Y J Kim PhD); School of Medical Sciences, University of Science Malaysia, Kubang Kerian, Malaysia (K I Musa MD); Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia (R Sahathevan PhD); Department of Community Medicine, International Medical University, Kuala Lumpur, Malaysia (C T Sreeramareddy MD); WorldFish, Penang, Malaysia (A L Thorne-Lyman ScD)

Matched MeSH terms: Mortality, Premature
Fulltext Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study

Muller DC, Murphy N, Johansson M, Ferrari P, Tsilidis KK, Boutron-Ruault MC, et al.

BMC Med, 2016 Jun 14;14:87.
PMID: 27296932 DOI: 10.1186/s12916-016-0630-6

BACKGROUND: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death.
METHODS: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models.
RESULTS: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31-32 %) and 14 % (95 % CI, 12-16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8-12 %) and high blood pressure (9 %; 95 % CI, 7-11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55-59 %), being 35 % (95 % CI, 32-37 %) among never smokers and 74 % (95 % CI, 73-75 %) among current smokers.
CONCLUSIONS: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.

Matched MeSH terms: Mortality, Premature*
Fulltext Predictor of cardiovascular risks in end stage renal failure patients on maintenance dialysis

Lim CT, Yap XH, Chung KJ, Khalid MA, Yayha N, Latiff LA, et al.

Pak J Med Sci, 2015 Nov-Dec;31(6):1300-5.
PMID: 26870086 DOI: 10.12669/pjms.316.8039

OBJECTIVE: Cardiovascular disease (CVD) is the main cause of morbidity and premature mortality in end stage renal failure patients (ESRD) receiving dialysis. The aim of our study was to evaluate the impact of various risk factors in this group of high CVD risk patients in local population.
METHODS: We carried out a cross-sectional retrospective study in a single hospital. A total of 136 ESRF patients, consisted of 43 haemodialysis (HD) and 93 continuous ambulatory peritoneal dialysis (CAPD) patients, were recruited and followed up for 36 months duration. Midweek clinical and laboratory data were collected. The occurrence of existing and new CVD events was recorded.
RESULTS: Multiple Logistic Regression showed pre-existing cardiovascular event (odds ratio, 4.124; 95% confidence interval [CI], 0.990 to 17.187), elevated total cholesterol level (odds ratio, 0.550; 95% CI, 0.315 to 0.963), elevated serum phosphate level (odds ratio, 5.862; 95% CI, 1.041 to 33.024) and elevated random blood glucose level (odds ratio, 1.193; 95% CI, 1.012 to 1.406) were significantly associated with occurrence of CVD events.
CONCLUSIONS: History of cardiovascular event before the initiation of dialysis, elevated level of serum phosphate and random blood glucose levels are the risk factors of CVD whereas paradoxically a high total cholesterol level has CVD protective effect towards the ESRF patients.
KEYWORDS: CVD risk; End Stage Renal Failure (ESRF); Haemodialysis; Peritoneal dialysis

Matched MeSH terms: Mortality, Premature
Fulltext The Kuwait National Primary Immunodeficiency Registry 2004-2018

Al-Herz W, Al-Ahmad M, Al-Khabaz A, Husain A, Sadek A, Othman Y

Front Immunol, 2019;10:1754.
PMID: 31396239 DOI: 10.3389/fimmu.2019.01754

Objective: To present the report from the Kuwait National Primary Immunodeficiency Registry between 2004 and 2018. Methods: The patients were followed prospectively between January 2004 and December 2018 and their collected data included sociodemographic, diagnosis, clinical presentation, laboratory tests, and treatment. Results: A total of 314 PID patients (165 males and 149 females) were registered during the study period. Most of the patients (n = 287, 91.4%) were Kuwaiti nationals and the prevalence among Kuwaitis was 20.27/100,000 with a cumulative incidence of 24.96/100,000 Kuwaitis. The distribution of the patients according to PID categories was as follow: immunodeficiencies affecting cellular and humoral immunity, 100 patients (31.8%); combined immunodeficiencies with associated syndromic features, 68 patients (21.7%); predominantly antibody deficiencies, 56 patients (17.8%); diseases of immune dysregulation, 47 patients (15%); congenital defects of phagocyte number or function, 20 patients (6.4%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 22 patients (7%). The mean age of the patients at onset of symptoms was 26 months while the mean age at diagnosis was 53 months and the mean delay in diagnosis was 27 months. Most of the patients (n = 272, 86%) had onset of symptoms before the age of 5 years. Parental consanguinity rate within the registered patients was 78% and a positive family history of PID was noticed in 50% of the patients. Genetic testing was performed in 69% of the patients with an overall diagnostic yield of 90%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by an autosomal recessive pattern. Intravenous immunoglobulins and stem cell transplantation were used in 58% and 25% of the patients, respectively. There were 81 deaths (26%) among the registered patients with a mean age of death of 25 months. Conclusions: PID is not infrequent in Kuwait and the reported prevalence is the highest in the literature with increased proportion of more severe forms. Collaborative efforts including introduction of newborn screening should be implemented to diagnose such cases earlier and improve the quality of life and prevent premature deaths.

Matched MeSH terms: Mortality, Premature

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