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1.
J Glob Health ; 9(2): 020701, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31673343

##### RESUMO

Background: Millennium Development Goal 4 (MDGs) mobilised countries to reduce child mortality by two thirds the 1990 rate in 2015. While India did not reach MDG 4, it considerably reduced child mortality in the MDG-era. Efficient and targeted interventions and adequate monitoring are necessary to further progress in improvements to child health. Looking forward to the Sustainable Development Goal (SDG)-era, the Indian Council of Medical Research and The INCLEN Trust International conducted a national research priority setting exercise for maternal, child, newborn health, and maternal and child nutrition. Here, results are reported for child health. Methods: The Child Health and Nutrition Research Initiative (CHNRI) method for research priority setting was employed. Research ideas were crowd-sourced from a network of child health experts from across India; these were refined and consolidated into research options (ROs) which were scored against five weighted criteria to arrive weighted Research Priority Scores (wRPS). National and regional priority lists were prepared. Results: 90 experts contributed 596 ideas that were consolidated into 101 research options (ROs). These were scored by 233 experts nationwide. National wRPS for ROs ranged between 0.92 and 0.51. The majority of the top research priorities related to development of cost-effective interventions and their implementation, and impact evaluations, improving data quality; and monitoring of existing programs, or improving the management of morbidities. The research priorities varied between regions, the Economic Action Group and North-Eastern states prioritised questions relating to delivering interventions at community- or household-level, whereas the North-Eastern states and Union Territories prioritised research questions involving managing and measuring malaria, and the Southern and Western states prioritised research questions involving pharmacovigilance of vaccines, impact of newly introduced vaccines, and delivery of vaccines to hard-to-reach populations. Conclusions: Research priorities varied geographically, according the stage of development of the area and mostly pertained to implementation sciences, which was expected given diversity in epidemiological profiles. Priority setting should help guide investment decisions by national and international agencies, therefore encouraging researchers to focus on priority areas. The ICMR has launched a grants programme for implementation research on maternal and child health to pursue research priorities identified by this exercise.

2.
JAMA Pediatr ; : 1-10, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589252

##### RESUMO

Importance: Reliable estimates of the prevalence of childhood hypertension serve as the basis for adequate prevention and treatment. However, the prevalence of childhood hypertension has rarely been synthesized at the global level. Objective: To conduct a systematic review and meta-analysis to assess the prevalence of hypertension in the general pediatric population. Data Sources: PubMed, MEDLINE, Embase, Global Health, and Global Health Library were searched from inception until June 2018, using search terms related to hypertension (hypertension OR high blood pressure OR elevated blood pressure), children (children OR adolescents), and prevalence (prevalence OR epidemiology). Study Selection: Studies that were conducted in the general pediatric population and quantified the prevalence of childhood hypertension were eligible. Included studies had blood pressure measurements from at least 3 separate occasions. Data Extraction and Synthesis: Two authors independently extracted data. Random-effects meta-analysis was used to derive the pooled prevalence. Variations in the prevalence estimates in different subgroups, including age group, sex, setting, device, investigation period, BMI group, World Health Organization region and World Bank region, were examined by subgroup meta-analysis. Meta-regression was used to establish the age-specific prevalence of childhood hypertension and to assess its secular trend. Main Outcomes and Measures: Prevalence of childhood hypertension overall and by subgroup. Results: A total of 47 articles were included in the meta-analysis. The pooled prevalence was 4.00% (95% CI, 3.29%-4.78%) for hypertension, 9.67% (95% CI, 7.26%-12.38%) for prehypertension, 4.00% (95% CI, 2.10%-6.48%) for stage 1 hypertension, and 0.95% (95% CI, 0.48%-1.57%) for stage 2 hypertension in children 19 years and younger. In subgroup meta-analyses, the prevalence of childhood hypertension was higher when measured by aneroid sphygmomanometer (7.23% vs 4.59% by mercury sphygmomanometer vs 2.94% by oscillometric sphygmomanometer) and among overweight and obese children (15.27% and 4.99% vs 1.90% among normal-weight children). A trend of increasing prevalence of childhood hypertension was observed during the past 2 decades, with a relative increasing rate of 75% to 79% from 2000 to 2015. In 2015, the prevalence of hypertension ranged from 4.32% (95% CI, 2.79%-6.63%) among children aged 6 years to 3.28% (95% CI, 2.25%-4.77%) among those aged 19 years and peaked at 7.89% (95% CI, 5.75%-10.75%) among those aged 14 years. Conclusions and Relevance: This study provides a global estimation of childhood hypertension prevalence based on blood pressure measurements in at least 3 separate visits. More high-quality epidemiologic investigations on childhood hypertension are still needed.

3.
Lancet Glob Health ; 7(8): e1020-e1030, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31303293

##### RESUMO

BACKGROUND: Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally. METHODS: For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle-brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model. FINDINGS: We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01-6·29, vs 3·54%, 1·17-10·24, at 40-44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22-28·90, vs 12·04%, 8·67-16·60, at 80-84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97-14·77, vs 6·60%, 3·74-11·38, at 55-59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06-8·05, vs 6·37%, 4·74-8·49, at 55-59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79-8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35-13·66, vs 5·09%, 3·64-7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015. INTERPRETATION: Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future. FUNDING: None.

4.
J Glob Health ; 9(1): 010102, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31263544
5.
Lancet Glob Health ; 7(6): e735-e747, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31097277

##### RESUMO

BACKGROUND: India accounts for a disproportionate burden of global childhood illnesses. To inform policies and measure progress towards achieving child health targets, we estimated the annual national and state-specific childhood mortality and morbidity attributable to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) between 2000 and 2015. METHODS: In this modelling study, we used vaccine clinical trial data to estimate the proportion of pneumonia deaths attributable to pneumococcus and Hib. The proportion of meningitis deaths attributable to each pathogen was derived from pathogen-specific meningitis case fatality and bacterial meningitis case data from surveillance studies. We applied these proportions to modelled state-specific pneumonia and meningitis deaths from 2000 to 2015 prepared by the WHO Maternal and Child Epidemiology Estimation collaboration (WHO/MCEE) on the basis of verbal autopsy studies from India. The burden of clinical and severe pneumonia cases attributable to pneumococcus and Hib was ascertained with vaccine clinical trial data and state-specific all-cause pneumonia case estimates prepared by WHO/MCEE by use of risk factor prevalence data from India. Pathogen-specific meningitis cases were derived from state-level modelled pathogen-specific meningitis deaths and state-level meningitis case fatality estimates. Pneumococcal and Hib morbidity due to non-pneumonia, non-meningitis (NPNM) invasive syndromes were derived by applying the ratio of pathogen-specific NPNM cases to pathogen-specific meningitis cases to the state-level pathogen-specific meningitis cases. Mortality due to pathogen-specific NPNM was calculated with the ratio of pneumococcal and Hib meningitis case fatality to pneumococcal and Hib meningitis NPNM case fatality. Census data from India provided the population at risk. FINDINGS: Between 2000 and 2015, estimates of pneumococcal deaths in Indian children aged 1-59 months fell from 166â000 (uncertainty range [UR] 110â000-198â000) to 68â700 (44â600-86â000), while Hib deaths fell from 82â600 (52â300-112â000) to 15â600 (9800-21â500), representing a 58% (UR 22-78) decline in pneumococcal deaths and an 81% (59-91) decline in Hib deaths. In 2015, national mortality rates in children aged 1-59 months were 56 (UR 37-71) per 100â000 for pneumococcal infection and 13 (UR 8-18) per 100â000 for Hib. Uttar Pradesh (18â900 [UR 12â300-23â600]) and Bihar (8600 [5600-10â700]) had the highest numbers of pneumococcal deaths in 2015. Uttar Pradesh (9300 [UR 5900-12â700]) and Odisha (1100 [700-1500]) had the highest numbers of Hib deaths in 2015. Less conservative assumptions related to the proportion of pneumonia deaths attributable to pneumococcus indicate that as many as 118â000 (UR 69â000-140â000) total pneumococcal deaths could have occurred in 2015 in India. INTERPRETATION: Pneumococcal and Hib mortality have declined in children aged 1-59 months in India since 2000, even before nationwide implementation of conjugate vaccines. Introduction of the Hib vaccine in several states corresponded with a more rapid reduction in morbidity and mortality associated with Hib infection. Rapid scale-up and widespread use of the pneumococcal conjugate vaccine and sustained use of the Hib vaccine could help accelerate achievement of child survival targets in India. FUNDING: Bill & Melinda Gates Foundation.

6.
J Glob Health ; 9(1): 010427, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31131101

##### RESUMO

Background: Retinal vein occlusion (RVO) is the second most common retinal vascular disorder that affected 16.4 million people worldwide in 2008. The last decade has seen new epidemiological data on RVO, enabling us to provide a contemporary estimation of RVO epidemiology. Methods: We searched PubMed, Medline, Embase, GLOBAL HEALTH, World Health Organization Global Health Library, China National Knowledge Infrastructure for studies that reported prevalence or incidence of RVO in the general population. The age- and sex-specific prevalence of RVO was estimated by a multilevel mixed-effects logistic regression, the incidence of RVO and potential risk factors for RVO were respectively pooled by a random-effects meta-analysis. Results: The prevalence of any RVO, branch RVO (BRVO) and central RVO (CRVO) all increased with advanced age, but didn't differ significantly between sexes. In 2015, the global prevalence of any RVO, BRVO and CRVO in people aged 30-89 years was 0.77% (95% confidence interval CI = 0.55-1.08), 0.64% (95% CI = 0.47-0.87) and 0.13% (95% CI = 0.08-0.21), equivalent to an overall of 28.06 million, 23.38 million and 4.67 million affected people. For any RVO, the pooled five-year cumulative incidence was 0.86% (95% CI = 0.70-1.07) and the pooled ten-year cumulative incidence was 1.63% (95% CI = 1.38-1.92). Hypertension was the strongest risk factor for any RVO, with a meta- odds ratio (OR) of 2.82 (95% CI = 2.12-3.75). Conclusions: This study provides an updated summary of RVO epidemiology in the general population. More epidemiological studies worldwide are still needed to better understand the global disease burden of RVO.

##### Assuntos
Saúde Global/estatística & dados numéricos , Oclusão da Veia Retiniana/epidemiologia , Humanos , Incidência , Prevalência , Fatores de Risco
7.
Thyroid ; 29(6): 886-893, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30929638

##### RESUMO

Background: Thyroglobulin (Tg) is a 660 kDa iodoglycoprotein that serves as a scaffold for thyroid hormone synthesis. Although a twin study showed that variability of serum Tg levels has a substantial genetic basis, no genome-wide association study (GWAS) of serum/plasma Tg levels has been performed to date. The aim of this study was to identify genetic variants associated with plasma Tg levels among healthy individuals. Methods: A GWAS was conducted on two Croatian cohorts, and a combined analysis was performed. The analyses included 1094 individuals. A total of 7,597,379 variants, imputed using the 1000 Genomes reference panel, were analyzed for association. GWAS was performed under an additive model, controlling for age, sex, and relatedness within each data set. Combined analysis was conducted using the inverse-variance fixed-effects method. Results: Sixteen variants located on chromosome 3, within the ST6GAL1 gene, reached genome-wide significance. The lead SNP was rs4012172 ( \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$p = 1.29 \times {10^{ - 10}}$$ \end{document} ), which explained 3.19% of the variance in Tg levels. ST6GAL1 belongs to the sialyltransferase protein family, which has a fundamental role in the synthesis of specific sialylated structures on various glycoproteins, including Tg. It is known that only immature Tg (poorly sialylated or desialylated) can be transferred to the bloodstream. Conclusions: A highly biologically plausible locus was identified that could have a role in the regulation of plasma Tg levels in healthy individuals.

8.
J Glob Health ; 9(1): 010702, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30992986

##### RESUMO

Introduction: Stakeholder involvement has been described as an indispensable part of health research priority setting. Yet, more than 75% of the exercises using the Child Health and Nutrition Research Initiative (CHNRI) methodology have omitted the step involving stakeholders in priority setting. Those that have used stakeholders have rarely used the public, possibly due to the difficulty of assembling and/or accessing a public stakeholder group. In order to strengthen future exercises using the CHNRI methodology, we have used a public stakeholder group to weight 15 CHNRI criteria, and have explored regional differences or being a health stakeholder is influential, and whether the criteria are collapsible. Methods: Using Amazon Mechanical Turk (AMT), an online crowdsourcing platform, we collected demographic information and conducted a Likert-scale format survey about the importance of the CHNRI criteria from 1051 stakeholders. The Kruskal-Wallis test, with Dunn's test for posthoc comparisons, was used to examine regional differences and Wilcoxon rank-sum test was used to analyse differences between stakeholders with health training/background and stakeholders without a health background and by region. A Factor Analysis (FA) was conducted on the criteria to identify the main domains connecting them. Criteria means were converted to weights. Results: There were regional differences in thirteen of fifteen criteria according to the Kruskal-Wallis test and differences in responses from health stakeholders vs those who were not in eleven of fifteen criteria using the Wilcoxon rank-sum test. Three components were identified: improve and impact results; implementation and affordability; and, study design and dissemination. A formula is provided to convert means to weights for future studies. Conclusion: In future CHNRI studies, researchers will need to ensure adequate representation from stakeholders to undue bias of CHNRI results. These results should be used in combination with other stakeholder groups, including government, donors, policy makers, and bilateral agencies. Global and regional stakeholder groups scored CHNRI criteria differently; due to this, researchers should consider which group to use in their CHNRI exercises.

##### Assuntos
Pesquisa Biomédica/organização & administração , Saúde da Criança , Participação dos Interessados , Adolescente , Adulto , Idoso , Crowdsourcing , Feminino , Saúde Global , Prioridades em Saúde , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
9.
Nutr Cancer ; 71(7): 1078-1085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30945952

##### RESUMO

25-Hydroxyvitamin D (25-OHD) may have a prognostic value in colorectal cancer (CRC) patients. However, as 25-OHD concentration is strongly impacted by surgery, it is uncertain what is the most reliable time-point for 25-OHD assessment, pre- or post-operative. Therefore, we examined 515 CRC patients (AJCC I-III) who underwent surgery. Blood samples were collected either pre-operatively (n = 286; median = 1 day before surgery) or post-operatively (n = 229; median = 8 days). Serum 25-OHD concentration was determined by liquid chromatography-tandem mass spectrometry. Association between 25-OHD and survival was tested in the whole cohort, followed by stratified analyses in pre- and post-operatively sampled. Median 25-OHD in the cohort was 36.7 nmol/L and median follow-up time was 5.9 years. There were no differences between pre- and post-operative cohort in age, sex, 25-OHD, AJCC stage, or localization of tumor. After adjustment, higher 25-OHD (>50 nmol/L) was associated with better overall survival only in post-operative (HR = 0.53; 95% CI: 0.33-0.84; P = 0.006), but not in pre-operative cohort (HR = 1.13; 95% CI: 0.77-1.65; P = 0.53). In conclusion, higher post-operative 25-OHD levels were associated with better survival outcome in CRC patients, while no such association was found for pre-operative levels. Time-point of blood collection should be addressed carefully in future research as it might affect the prognostic value of 25-OHD in CRC.

10.
J Glob Health ; 9(1): 010601, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30873278

##### Assuntos
Doença Arterial Periférica/epidemiologia , China/epidemiologia , Humanos , Prevalência
11.
J Glob Health ; 9(1): 010422, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30842883

##### RESUMO

Objectives: Medication errors continue to contribute substantially to global morbidity and mortality. In the context of the recent launch of the World Health Organization's (WHO) Third Global Patient Safety Challenge: Medication Without Harm, we sought to establish agreement on research priorities for medication safety. Methods: We undertook a consensus prioritisation exercise using an approach developed by the Child Health and Nutrition Research Initiative. Based on a combination of productivity and citations, we identified leading researchers in patient and medication safety and invited them to participate. We also extended the invitation to a further pool of experts from the WHO Global Patient Safety Network. All experts independently generated research ideas, which they then independently scored based on the criteria of: answerability, effectiveness, innovativeness, implementation, burden reduction and equity. An overall Research Priority Score and Average Expert Agreement were calculated for each research question. Findings: 131 experts submitted 333 research ideas, and 42 experts then scored the proposed research questions. The top prioritised research areas were: (1) deploying and scaling technology to enhance medication safety; (2) developing guidelines and standard operating procedures for high-risk patients, medications and contexts; (3) score-based approaches to predicting high-risk patients and situations; (4) interventions to increase patient medication literacy; (5) focused training courses for health professionals; and (6) universally applicable pictograms to avoid medication-related harm. Whilst there was a focus on promoting patient education and involvement across resource settings, priorities identified in high-resource settings centred on the optimisation of existing systems through technology. In low- and middle-resource settings, priorities focused on identifying systemic issues contributing to high-risk situations. Conclusions: WHO now plans to work with global, regional and national research funding agencies to catalyse the investment needed to enable teams to pursue these research priorities in medication safety across high-, middle- and low-resource country settings.

##### Assuntos
Consenso , Saúde Global , Erros de Medicação/prevenção & controle , Segurança do Paciente , Pesquisa/organização & administração , Humanos
12.
J Glob Health ; 9(1): 010701, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30820318

##### RESUMO

Introduction: The Child Health and Nutrition Research Initiative (CHNRI) method for health research prioritisation relies on stakeholders weighting criteria used to assess research options. These weights in turn impact on the final scores and ranks assigned to research options. Three quarters of CHNRI studies published to date have not involved stakeholders in criteria weighting. Of those that have, few incorporated members of the public into stakeholder groups. Those that have compared different stakeholder groups, such as donors, researchers, or policy makers, showed that different groups place different values upon CHNRI criteria. When choosing the composition of a stakeholder group, it may be important to understand factors that may influence weighting. Drawing upon a group of international public stakeholders, this study explores some of the effects of individual and demographic characteristics has on the weights assigned to the most commonly used CHNRI criteria, with the aim of informing future researchers on avoiding future biases. Methods: Individual and demographic information and 5-point Likert scale responses to questions about the importance of 15 CHNRI criteria were collected from 1031 "Turkers" (Amazon Mechanical Turk workers) via Amazon Mechanical Turk (AMT), which is an online crowdsourcing platform. Thirteen of the fifteen criteria were analysed using random-intercept models and the remaining two were analysed through logistic regression. Results: Self-reported health status explained most of the variability in participants' responses across criteria (11/15 criteria), followed by being female (10/15), ethnicity (9/15), employment (8/15), and religion (7/15). Differences across criteria indicate that when choosing stakeholder groups, researchers need to consider these factors to minimise bias. Conclusion: Researchers should collect and report more detailed information from stakeholders, including individual and demographic characteristics, and ensure participation from both genders, multiple ethnicities, religious beliefs, and people with differing health statuses to be transparent regarding possible biases in health research prioritisation. Our analyses indicate that these factors do influence the relative importance of these values, even when the data appears fairly homogeneous.

##### Assuntos
Pesquisa Biomédica , Prioridades em Saúde , Participação dos Interessados , Adolescente , Adulto , Idoso , Saúde da Criança , Demografia , Feminino , Saúde Global , Humanos , Individualidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Ciências da Nutrição , Adulto Jovem
13.
Circulation ; 139(5): 620-635, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30586737

##### RESUMO

BACKGROUND: Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF. METHODS: We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events. RESULTS: We identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk. CONCLUSIONS: The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.

14.
Lancet Glob Health ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30497986

##### RESUMO

BACKGROUND: Global child mortality reduced substantially during the Millennium Development Goal period (2000-15). We aimed to estimate morbidity, mortality, and prevalence of risk factors for child pneumonia at the global, regional, and national level for developing countries for the Millennium Development Goal period. METHODS: We estimated the incidence, number of hospital admissions, and in-hospital mortality due to all-cause clinical pneumonia in children younger than 5 years in developing countries at 5-year intervals during the Millennium Development Goal period (2000-15) using data from a systematic review and Poisson regression. We estimated the incidence and number of cases of clinical pneumonia, and the pneumonia burden attributable to HIV for 132 developing countries using a risk-factor-based model that used Demographic and Health Survey data on prevalence of the various risk factors for child pneumonia. We also estimated pneumonia mortality in young children using data from multicause models based on vital registration and verbal autopsy. FINDINGS: Globally, the number of episodes of clinical pneumonia in young children decreased by 22% from 178 million (95% uncertainty interval [UI] 110-289) in 2000 to 138 million (86-226) in 2015. In 2015, India, Nigeria, Indonesia, Pakistan, and China contributed to more than 54% of all global pneumonia cases, with 32% of the global burden from India alone. Between 2000 and 2015, the burden of clinical pneumonia attributable to HIV decreased by 45%. Between 2000 and 2015, global hospital admissions for child pneumonia increased by 2·9 times with a more rapid increase observed in the WHO South-East Asia Region than the African Region. Pneumonia deaths in this age group decreased from 1·7 million (95% UI 1·7-2·0) in 2000 to 0·9 million (0·8-1·1) in 2015. In 2015, 49% of global pneumonia deaths occurred in India, Nigeria, Pakistan, Democratic Republic of the Congo, and Ethiopia collectively. All key risk factors for child pneumonia (non-exclusive breastfeeding, crowding, malnutrition, indoor air pollution, incomplete immunisation, and paediatric HIV), with the exception of low birthweight, decreased across all regions between 2000 and 2015. INTERPRETATION: Globally, the incidence of child pneumonia decreased by 30% and mortality decreased by 51% during the Millennium Development Goal period. These reductions are consistent with the decrease in the prevalence of some of the key risk factors for pneumonia, increasing socioeconomic development and preventive interventions, improved access to care, and quality of care in hospitals. However, intersectoral action is required to improve socioeconomic conditions and increase coverage of interventions targeting risk factors for child pneumonia to accelerate decline in pneumonia mortality and achieve the Sustainable Development Goals for health by 2030. FUNDING: Bill & Melinda Gates Foundation.

15.
J Glob Health ; 8(2): 021103, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30574296

##### RESUMO

Background: Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes. Methodology: We performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region. Results: 67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe. Conclusion: There were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood.

##### Assuntos
Anemia Falciforme/epidemiologia , Efeitos Psicossociais da Doença , Saúde Global/estatística & dados numéricos , Pré-Escolar , Humanos , Lactente , Recém-Nascido
16.
J Glob Health ; 8(2): 021101, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30410744

##### RESUMO

Background: Epidemiology of type 1 diabetes mellitus (T1DM) among children aged 0-4 years globally is not well understood. We aim to assess the incidence of T1DM in low- and middle-income countries (LMIC) by conducting a systematic review of previous reports. We also aim to address possible contribution to child mortality and to identify any temporal trends. Methods: A systematic review was performed using a carefully designed search strategy to explore MEDLINE, EMBASE and Global Health databases. Data was extracted from all studies that satisfied the inclusion criteria -a total of 83 records extracted from 26 830 sources that were analysed. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process to assess quality of evidence and applied meta-analysis approaches to assess global and regional incidence and time trends. Results: The overall pooled incidence of T1DM in children aged 0-4 years globally is 11.2 (95% CI = 10.0-12.3) per 100 000 child years. The regional incidence were the highest for European Region A (EUR A) at 15.5 (95% CI = 13.5-17.5) per 100 000 child years. EUR C had the incidence of 10.0 (95% CI = 6.5-13.6) and EUR B 5.8 (95% CI = 4.7-7.0), Region of the Americas A (AMR A) 11.4 (95% CI = 7.8-14.9), AMR B of 2.5 (95% CI = 0.2-4.8), Eastern Mediterranean Region (EMR B) 7.1 (95% CI = 4.2-10.0) and Western Pacific Region (WPR A) 7.0 (95% CI = 2.9-11.0) per 100 000 child years, while other regions had very low rates or no data. When data points were categorised in the study periods and re-analysed, an increasing trend of the T1DM incidence was observed, with the incidence of 20.9 (95% CI = 7.8-34.1) per 100 000 child years in the years 2010-2015, preceded by 13.2 (95% CI = 11.0-15.5) in 2000-2009 study period, 10.0 (95% CI = 8.4-11.7) in 1990-1999 and 8.3 (95% CI = 5.1-11.6) in 1980-1989, respectively. Although the data are scarce, and variation and uncertainty are large, we estimated that the number of new cases of T1DM among children aged 0-4 years in the world each year is between 100 000 and 150 000. Conclusions: The identified large variation in incidence estimates for different parts of the world, along with scarcity of information and the identified strong temporal increase in T1DM incidence suggest a clear need for further research into this subject.

##### Assuntos
Países em Desenvolvimento , Diabetes Mellitus Tipo 1/epidemiologia , Saúde Global/estatística & dados numéricos , Pré-Escolar , Humanos , Incidência , Lactente , Recém-Nascido , Morbidade/tendências
17.
J Glob Health ; 8(2): 021102, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30479748

##### RESUMO

Background: Inborn errors of metabolism (IEM) are a group of over 500 heterogeneous disorders resulting from a defect in functioning of an intermediate metabolic pathway. Individually rare, their cumulative incidence is thought to be high, but it has not yet been estimated globally. Although outcomes can often be good if recognised early, IEM carry a high fatality rate if not diagnosed. As a result, IEM may contribute significantly to the burden of non-communicable childhood morbidity. Methods: We conducted a systematic literature review of birth prevalence and case fatality of IEM globally, with search dates set from 1980 to 2017. Using random-effects meta-analysis, we estimated birth prevalence of separate classes of IEM and all-cause IEM, split by geographical region. We also estimated levels of parental consanguinity in IEM cases and global case fatality rates and resultant child deaths from all-cause IEM. Findings: 49 studies met our selection criteria. We estimate the global birth prevalence of all-cause IEM to be 50.9 per 100 000 live births (95% confidence intervals (CI) = 43.4-58.4). Regional pooled birth prevalence rates showed the highest rates of IEM to be in the Eastern Mediterranean region (75.7 per 100 000 live births, 95% CI = 50.0-101.4), correlating with a higher observed rate of parental consanguinity in studies from this area. We estimate case fatality rates to be 33% or higher in low- and middle-income countries (LMICs), resulting in a minimum of 23 529 deaths from IEM per year globally (95% CI = 20 382-27 427), accounting for 0.4% of all child deaths worldwide. Conclusions: IEM represent a significant cause of global child morbidity and mortality, comprising a notable proportion of child deaths currently not delineated in global modelling efforts. Our data highlight the need for policy focus on enhanced laboratory capacity for screening and diagnosis, community interventions to tackle parental consanguinity, and increased awareness and knowledge regarding management of IEM, particularly in LMICs.

18.
J Glob Health ; 8(2): 020702, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30356511

##### RESUMO

Background: In 2015, it was estimated that the burden of disease in Iran comprised of 19 million disability-adjusted life years (DALYs), 74% of which were due to non-communicable diseases (NCDs). The observed leading causes of death were cardiovascular diseases (41.9%), neoplasms (14.9%), and road traffic injuries (7.4%). Even so, the health research investment in Iran continues to remain limited. This study aims to identify national health research priorities in Iran for the next five years to assist the efficient use of resources towards achieving the long-term health targets. Methods: Adapting the Child Health and Nutrition Research Initiative (CHNRI) method, this study engaged 48 prominent Iranian academic leaders in the areas related to Iran's long-term health targets, a group of research funders and policy makers, and 68 stakeholders from the wider society. 128 proposed research questions were scored independently using a set of five criteria: feasibility, impact on health, impact on economy, capacity building, and equity. Findings: The top-10 priorities were focused on the research questions relating to: health insurance system reforms to improve equity; integration of NCDs prevention strategy into primary health care; cost-effective population-level interventions for NCDs and road traffic injury prevention; tailoring medical qualifications; epidemiological assessment of NCDs by geographic areas; equality in the distribution of health resources and services; current and future common health problems in Iran's elderly and strategies to reduce their economic burden; the status of antibiotic resistance in Iran and strategies to promote rational use of antibiotics; the health impacts of water crisis; and research to replace the physician-centered health system with a team-based one. Conclusions: These findings highlight consensus amongst various prominent Iranian researchers and stakeholders over the research priorities that require investment to generate information and knowledge relevant to the national health targets and policies. The exercise should assist in addressing the knowledge gaps to support both the National General Health Policies by 2025 and the health targets of the United Nations' Sustainable Development Goals by 2030.

##### Assuntos
Pesquisa/organização & administração , Causas de Morte/tendências , Pessoas com Deficiência/estatística & dados numéricos , Metas , Humanos , Irã (Geográfico)/epidemiologia , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/prevenção & controle , Anos de Vida Ajustados por Qualidade de Vida
19.
J Glob Health ; 8(2): 020503, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30206477

##### RESUMO

Background: Dry eye disease (DED) is one of the most prevalent ocular diseases in the world. In China, new lifestyles driven by information technology and the rapid ageing process have brought DED a severe public health concern. The aim of our study was to obtain the pooled prevalence of DED in China and explore its potential correlates. Methods: A comprehensive systematic review was conducted to identify all relevant literature published since 1990. Meta-analysis and meta-regression approaches were adopted to estimate the prevalence of DED. The number of people with DED was obtained by multiplying the corresponding demographic data in 2010. Results: Advanced age, female sex and larger latitude were significant risk factors for DED by symptoms and signs, whereas only advanced age was positively associated with an increased prevalence of DED by symptoms. In 2010, the prevalence of DED by symptoms and signs were 13.55% (95% CI = 10.00-18.05) and that of DED by symptoms was 31.40% (95% CI = 23.02-41.13) in Chinese people aged 5-89 years, corresponding to a total of 170.09 million (95% CI = 125.52-226.63) and 394.13 million (95% CI = 288.99-516.30) affected individuals respectively. Conclusions: The huge burden of DED in China calls for more public health attention and actions. Improved epidemiological studies on DED prevalence are still urgently needed.

##### Assuntos
Síndromes do Olho Seco/epidemiologia , Disparidades nos Níveis de Saúde , Distribuição por Idade , China/epidemiologia , Feminino , Geografia , Humanos , Masculino , Prevalência , Fatores de Risco , Distribuição por Sexo
20.
J Glob Health ; 8(1): 010102, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29977523