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1.
Am J Epidemiol ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914184

RESUMO

Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications on results of three influenza mortality projects from the United States Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; IHME estimate was considerably lower. The greatest country-specific influenza-associated mortality rate fold differences between CDC/IHME and between GLaMOR/IHME estimates were among countries in South-East Asia and Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: low respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other two groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally.

2.
Nat Hum Behav ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989287

RESUMO

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

3.
Lancet Respir Med ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32971018

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is the predominant viral pathogen associated with acute lower respiratory infection (ALRI) in children who are younger than 5 years. Little is reported on the national estimates of RSV-associated ALRI hospitalisations in these children on the basis of robust epidemiological data. We aimed to generate national level estimates for RSV-associated ALRI hospitalisations in children aged younger than 5 years. METHODS: We included data for RSV and ALRI hospitalisation in children who were younger than 5 years from systematic literature reviews (including unpublished data) and from inpatient databases, representing 58 countries. We used two different methods, the rate-based method and the proportion-based method, to estimate national RSV-associated ALRI hospitalisations in children younger than 5 years in 2019. The rate-based method synthesised data for laboratory-confirmed RSV-associated ALRI hospitalisation rates using a spatiotemporal Gaussian process meta-regression (ST-GPR). The proportion-based method applied data for RSV positive proportions among ALRI to all-cause ALRI hospitalisation envelopes (ie, total disease burden of ALRI hospitalisations of any cause) using a Bayesian regularised trimmed meta-regression (MR-BRT). Where applicable, we reported estimates by both methods to provide a plausible range for each country. FINDINGS: A total of 334 studies and 1985 data points (defined as an individual estimate for one age group and 1 year for each study) were included in our analysis, accounting for 398 million (59%) of the 677 million children aged younger than 5 years worldwide representing 58 countries. We reported the number of annual national RSV-associated ALRI hospitalisations for 29 countries using the rate-based method, and for 42 countries using the proportion-based method. The median number of RSV-associated ALRI hospitalisations in children younger than 5 years was 8·25 thousand (IQR 1·97-48·01), and the median rate of RSV-associated ALRI hospitalisations was 514 (339-866) hospitalisations per thousand children younger than 5 years. Despite large variation among countries, a high proportion of the RSV-associated ALRI hospitalisations were in infants aged younger than 1 year in all countries (median proportion 45%, IQR 32-56). In 272 (76%) of the 358 years included in the analysis, the RSV-associated ALRI hospitalisation rate fluctuated between 0·8 and 1·2 times the country's median yearly rate. General agreement was observed between estimates by the rate-based method and proportion-based method, with the exceptions of India, Kenya, Norway, and Philippines. INTERPRETATION: By incorporating data from various sources, our study provides robust estimates on national level burden of RSV-associated ALRI hospitalisation in children aged younger than 5 years. These estimates are important for informing policy for the introduction of RSV immunisations and also serve as baseline data for the RSV disease burden in young children. FUNDING: The Foundation for Influenza Epidemiology.

4.
Aging (Albany NY) ; 12(15): 15222-15259, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788422

RESUMO

Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. Composition of the IgG N-glycome changes with age of an individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is known to be affected by both genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of IgG, analyzed in 5 different populations totaling 10,482 IgG glycomes, and of IgG's fragment crystallizable region (Fc), analyzed in 2,579 samples from 27 populations sampled across the world. Country of residence associated with many N-glycan features and the strongest association was with monogalactosylation where it explained 38% of variability. IgG monogalactosylation strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators, and with the expected lifespan. Subjects from developing countries had low levels of IgG galactosylation, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

5.
J Infect Dis ; 222(Supplement_7): S592-S598, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32794556

RESUMO

BACKGROUND: Bronchiolitis is the commonest cause of respiratory related hospital admissions in young children. This study aimed to describe temporal trends in bronchiolitis admissions for children under 2 years of age in Scotland by patient characteristics, socioeconomic deprivation, and duration of admission. METHODS: The national hospital admissions database for Scotland was used to extract data on all bronchiolitis admissions (International Classification of Disease, Tenth Revision, code J21) in children <2 years of age from 2001 to 2016. Deprivation quintiles were classified using the 2011 Scottish Index of Multiple Deprivation. RESULTS: Over the 15-year study period, admission rates for children under 2 years old increased 2.20-fold (95% confidence interval [CI], 1.4-3.6-fold) from 17.2 (15.9-18.5) to 37.7 (37.4-38.1) admissions per 1000 children per year. Admissions peaked in infants aged 1 month, and in those born in the 3 months preceding the peak bronchiolitis month-September, October, and November. Admissions from the most-deprived quintile had the highest overall rate of admission, at 40.5 per 1000 children per year (95% CI, 39.5-41.5) compared with the least-deprived quintile, at 23.0 admissions per 1000 children per year (22.1-23.9). The most-deprived quintile had the greatest increase in admissions over time, whereas the least-deprived quintile had the lowest increase. Zero-day admissions, defined as admission and discharge within the same calendar date, increased 5.3-fold (5.1-5.5) over the study period, with the highest increase in patients in the most-deprived quintile. CONCLUSIONS: This study provides baseline epidemiological data to aid policy makers in the strategic planning of preventative interventions. With the majority of bronchiolitis caused by respiratory syncytial virus (RSV), and several RSV vaccines and monoclonal antibodies currently in clinical trials, understanding national trends in bronchiolitis admissions is an important proxy for determining potential RSV vaccination strategies.

6.
J Infect Dis ; 222(Supplement_7): S634-S639, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32794576

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV)-related acute lower respiratory infection is an important cause of death in infants and young children. However, little is known about the risk period for RSV-related deaths after presentation to health services with an RSV illness. METHODS: Using the Scottish national mortality database, we identified deaths from respiratory/circulatory causes (hereafter "respiratory/circulatory deaths") in young children aged <5 years during 2009-2016, whose medical history and records of laboratory-confirmed RSV infections were obtained by linking the mortality database to the national surveillance data set and the Scottish Morbidity Record. We used a self-controlled case series (SCCS) design to evaluate the relative incidence of deaths with respiratory/circulatory deaths in the first year after an RSV episode. We defined the risk interval as the first year after the RSV episode, and the control interval as the period before and after the risk interval until 5 years after birth. Age-adjusted incidence ratio and attributable fraction were generated using the R software package SCCS. RESULTS: We included 162 respiratory/circulatory deaths, of which 36 occurred in children with a history of laboratory-confirmed RSV infection. We found that the mortality risk decreased with time after the RSV episode and that the risk was statistically significant for the month after RSV illness. More than 90% of respiratory/circulatory deaths occurring within 1 week after the RSV episode were attributable to RSV (attributable fraction, 93.9%; 95% confidence interval, 77.6%-98.4%), compared with about 80% of those occurring 1 week to 1 month after RSV illness (80.3%; 28.5%-94.6%). CONCLUSIONS: We found an increased risk of death in the first month after an RSV illness episode leading to healthcare attendance. This provides a practical cutoff time window for community-based surveillance studies estimating RSV-related mortality risk. Further studies are warranted to assess the mortality risk beyond the first month after RSV illness episode.

7.
J Infect Dis ; 222(Supplement_7): S599-S605, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32815542

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection (RTI) in young children. Registries provide opportunities to explore RSV epidemiology and burden. METHODS: We explored routinely collected hospital data on RSV in children aged < 5 years in 7 European countries. We compare RSV-associated admission rates, age, seasonality, and time trends between countries. RESULTS: We found similar age distributions of RSV-associated hospital admissions in each country, with the highest burden in children < 1 years old and peak at age 1 month. Average annual rates of RTI admission were 41.3-112.0 per 1000 children aged < 1 year and 8.6-22.3 per 1000 children aged < 1 year. In children aged < 5 years, 57%-72% of RTI admissions with specified causal pathogen were coded as RSV, with 62%-87% of pathogen-coded admissions in children < 1 year coded as RSV. CONCLUSIONS: Our results demonstrate the benefits and limitations of using linked routinely collected data to explore epidemiology and burden of RSV. Our future work will use these data to generate estimates of RSV burden using time-series modelling methodology, to inform policymaking and regulatory decisions regarding RSV immunization strategy and monitor the impact of future vaccines.

8.
J Infect Dis ; 222(Supplement_7): S688-S694, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32821916

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. METHODS: Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012-2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. RESULTS: Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20-64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. CONCLUSIONS: Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0-5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits.

9.
BMJ Glob Health ; 5(8)2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32792409

RESUMO

INTRODUCTION: Healthcare providers in resource-limited settings rely on the presence of tachypnoea and chest indrawing to establish a diagnosis of pneumonia in children. We aimed to determine the test characteristics of commonly assessed signs and symptoms for the radiographic diagnosis of pneumonia in children 0-59 months of age. METHODS: We conducted an analysis using patient-level pooled data from 41 shared datasets of paediatric pneumonia. We included hospital-based studies in which >80% of children had chest radiography performed. Primary endpoint pneumonia (presence of dense opacity occupying a portion or entire lobe of the lung or presence of pleural effusion on chest radiograph) was used as the reference criterion radiographic standard. We assessed the sensitivity, specificity, and likelihood ratios for clinical findings, and combinations of findings, for the diagnosis of primary endpoint pneumonia among children 0-59 months of age. RESULTS: Ten studies met inclusion criteria comprising 15 029 children; 24.9% (n=3743) had radiographic pneumonia. The presence of age-based tachypnoea demonstrated a sensitivity of 0.92 and a specificity of 0.22 while lower chest indrawing revealed a sensitivity of 0.74 and specificity of 0.15 for the diagnosis of radiographic pneumonia. The sensitivity and specificity for oxygen saturation <90% was 0.40 and 0.67, respectively, and was 0.17 and 0.88 for oxygen saturation <85%. Specificity was improved when individual clinical factors such as tachypnoea, fever and hypoxaemia were combined, however, the sensitivity was lower. CONCLUSIONS: No single sign or symptom was strongly associated with radiographic primary end point pneumonia in children. Performance characteristics were improved by combining individual signs and symptoms.

10.
Lancet Child Adolesc Health ; 4(9): 678-687, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32827490

RESUMO

BACKGROUND: The absolute number of pneumonia deaths in India has declined substantially since 2000. However, pneumonia remains a major cause of morbidity in children in the country. We used a risk factor-based model to estimate pneumonia and severe pneumonia morbidity in Indian states in 2000 and 2015. METHODS: In this modelling study, we estimated the burden of pneumonia and severe pneumonia in children younger than 5 years using a risk factor-based model. We did a systematic literature review to identify published data on the incidence of pneumonia from community-based longitudinal studies and calculated summary estimates. We estimated state-specific incidence rates for WHO-defined clinical pneumonia between 2000 and 2015 using Poisson regression and the prevalence of risk factors in each state was obtained from National Family Health Surveys. From clinical pneumonia studies, we identified studies reporting the proportion of clinical pneumonia cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases. We used the estimate of the proportion of cases with lower chest wall indrawing to estimate WHO-defined severe pneumonia cases for each state. FINDINGS: Between 2000 and 2015, the estimated number of pneumonia cases in Indian HIV-uninfected children younger than 5 years decreased from 83·8 million cases (95% uncertainty interval [UI] 14·0-300·8) to 49·8 million cases (9·1-174·2), representing a 41% reduction in pneumonia cases. The incidence of pneumonia in children younger than 5 years in India was 657 cases per 1000 children (95% UI 110-2357) in 2000 and 403 cases per 1000 children (74-1408) in 2015. The estimated national pneumonia case fatality rate in 2015 was 0·38% (95% UI 0·11-2·10). In 2015, the estimated number of severe pneumonia cases was 8·4 million (95% UI 1·2-31·7), with an incidence of 68 cases per 1000 children (9-257) and a case fatality ratio of 2·26% (0·60-16·30). In 2015, the estimated number of pneumonia cases in HIV-uninfected children was highest in Uttar Pradesh (12·4 million [95% UI 2·1-45·0]), Bihar (7·3 million [1·3-26·1]), and Madhya Pradesh (4·6 million [0·7-17·0]). Between 2000 and 2015, the greatest reduction in pneumonia cases was observed in Kerala (82% reduction). In 2015, pneumonia incidence was greater than 500 cases per 1000 children in two states: Uttar Pradesh (565 cases per 1000 children [95% UI 94-2047]) and Madhya Pradesh (563 cases per 1000 children [88-2084]). INTERPRETATION: The estimated number of pneumonia and severe pneumonia cases among children younger than 5 years in India decreased between 2000 and 2015. Improvements in socioeconomic indicators and specific government initiatives are likely to have contributed to declines in the prevalence of pneumonia risk factors in many states. However, pneumonia incidence in many states remains high. The introduction of new vaccines that target pneumonia pathogens and reduce risk factors will help further reduce the burden of pneumonia in the country. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Pneumonia/epidemiologia , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Índia/epidemiologia , Masculino , Vigilância da População , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
12.
Int J Cancer ; 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32638365

RESUMO

Increasing numbers of common genetic variants associated with colorectal cancer (CRC) have been identified. Our study aimed to determine whether risk prediction based on common genetic variants might enable stratification for CRC risk. Meta-analysis of 11 genome-wide association studies comprising 16 871 cases and 26 328 controls was performed to capture CRC susceptibility variants. Genetic prediction models with several candidate polygenic risk scores (PRSs) were generated from Scottish CRC case-control studies (6478 cases and 11 043 controls) and the score with the best performance was then tested in UK Biobank (UKBB) (4800 cases and 20 287 controls). A weighted PRS of 116 CRC single nucleotide polymorphisms (wPRS116 ) was found with the best predictive performance, reporting a c-statistics of 0.60 and an odds ratio (OR) of 1.46 (95% confidence interval [CI] = 1.41-1.50, per SD increase) in Scottish data set. The predictive performance of this wPRS116 was consistently validated in UKBB data set with c-statistics of 0.61 and an OR of 1.49 (95% CI = 1.44-1.54, per SD increase). Modeling the levels of PRS with age and sex in the general UK population shows that employing genetic risk profiling can achieve a moderate degree of risk discrimination that could be helpful to identify a subpopulation with higher CRC risk due to genetic susceptibility.

13.
PLoS Genet ; 16(7): e1008785, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628676

RESUMO

To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances from GeneAtlas (UK Biobank), 77 showed little evidence of pleiotropy (HEIDI), and 92 evidence of colocalization (eCAVIAR). Results were wide ranging: including, for example, new evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia, and a new finding that intestinal fatty acid binding protein (FABP2) abundance contributes to the pathogenesis of cardiovascular disease. We also demonstrated confirmatory evidence for the causal role of four further proteins (FGF5, IL6R, LPL, LTA) in cardiovascular disease risk.


Assuntos
Doenças Cardiovasculares/genética , Análise da Randomização Mendeliana , Proteoma/genética , Esquizofrenia/genética , Antígenos de Diferenciação/genética , Doenças Cardiovasculares/patologia , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Fator 5 de Crescimento de Fibroblastos/genética , Estudos de Associação Genética/métodos , Humanos , Lipase Lipoproteica/genética , Linfotoxina-alfa/genética , Masculino , Locos de Características Quantitativas , Receptores Imunológicos/genética , Receptores de Interleucina-6/genética , Esquizofrenia/patologia
14.
Glycobiology ; 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32521004

RESUMO

Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identified by three previous GWAS of human plasma proteome N-glycosylation. However, the possibility that some of these loci are false positives needs to be eliminated by replication studies, which have been limited so far. Here, we use the largest set of samples so far (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen were replicated in our study. For the remaining locus (near the KREMEN1 gene) the replication power was low, and hence replication results were inconclusive. The very high replication rate highlights the general robustness of the GWAS findings as well as the high standards adopted by the community that studies genetic regulation of protein glycosylation. The fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode glycosyltransferases: MGAT5, B3GAT1, FUT8, FUT6, ST6GAL1, B4GALT1, ST3GAL4, and MGAT3. The remaining seven loci offer starting points for further functional follow-up investigation into molecules and mechanisms that regulate human protein N-glycosylation in vivo.

17.
J Glob Health ; 10(1): 010602, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32426124

RESUMO

Introduction: Common approaches to measure health behaviors rely on participant responses and are subject to bias. Technology-based alternatives, particularly using GPS, address these biases while opening new channels for research. This study describes the development and implementation of a GPS-based approach to detect health facility visits in rural Pune district, India. Methods: Participants were mothers of under-five year old children within the Vadu Demographic Surveillance area. Participants received GPS-enabled smartphones pre-installed with a location-aware application to continuously record and transmit participant location data to a central server. Data were analyzed to identify health facility visits according to a parameter-based approach, optimal thresholds of which were calibrated through a simulation exercise. Lists of GPS-detected health facility visits were generated at each of six follow-up home visits and reviewed with participants through prompted recall survey, confirming visits which were correctly identified. Detected visits were analyzed using logistic regression to explore factors associated with the identification of false positive GPS-detected visits. Results: We enrolled 200 participants and completed 1098 follow-up visits over the six-month study period. Prompted recall surveys were completed for 694 follow-up visits with one or more GPS-detected health facility visits. While the approach performed well during calibration (positive predictive value (PPV) 78%), performance was poor when applied to participant data. Only 440 of 22 251 detected visits were confirmed (PPV 2%). False positives increased as participants spent more time in areas of high health facility density (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.62-3.25). Visits detected at facilities other than hospitals and clinics were also more likely to be false positives (OR = 2.78, 95% CI = 1.65-4.67) as were visits detected to facilities nearby participant homes, with the likelihood decreasing as distance increased (OR = 0.89, 95% CI = 0.82-0.97). Visit duration was not associated with confirmation status. Conclusions: The optimal parameter combination for health facility visits simulated by field workers substantially overestimated health visits from participant GPS data. This study provides useful insights into the challenges in detecting health facility visits where providers are numerous, highly clustered within urban centers and located near residential areas of the population which they serve.


Assuntos
Utilização de Instalações e Serviços/estatística & dados numéricos , Sistemas de Informação Geográfica , Instalações de Saúde/estatística & dados numéricos , Rememoração Mental , Mães/psicologia , Adolescente , Adulto , Pré-Escolar , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Índia , Lactente , Pessoa de Meia-Idade , Mães/estatística & dados numéricos , Reprodutibilidade dos Testes , População Rural/estatística & dados numéricos , Smartphone , Adulto Jovem
18.
Cancer Med ; 9(13): 4823-4835, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32400092

RESUMO

Several associations between non-genetic biomarkers and colorectal cancer (CRC) risk have been detected, but the strength of evidence and the direction of associations are not confirmed. We aimed to evaluate the evidence of these associations and integrate results from different approaches to assess causal inference. We searched Medline and Embase for meta-analyses of observational studies, meta-analyses of randomized clinical trials (RCTs), and Mendelian randomization (MR) studies measuring the associations between non-genetic biomarkers and CRC risk and meta-analyses of RCTs on supplementary micronutrients. We repeated the meta-analyses using random-effects models and categorized the evidence based on predefined criteria. We described each MR study and evaluated their credibility. Seventy-two meta-analyses of observational studies and 18 MR studies on non-genetic biomarkers and six meta-analyses of RCTs on micronutrient intake and CRC risk considering 65, 42, and five unique associations, respectively, were identified. No meta-analyses of RCTs on blood level biomarkers have been found. None of the associations were classified as convincing or highly suggestive, three were classified as suggestive, and 26 were classified as weak. For three biomarkers explored in MR studies, there was evidence of causality and seven were classified as likely noncausal. For the first time, results from both observational and MR studies were integrated by triangulating the evidence for a wide variety of non-genetic biomarkers and CRC risk. At blood level, lower vitamin D, higher homeostatic model assessment-insulin resistance, and human papillomavirus infection were associated with higher CRC risk while increased linoleic acid and oleic acid and decreased arachidonic acid were likely causally associated with lower CRC risk. No association was found convincing in both study types.

19.
J Glob Health ; 10(1): 010801, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32257166

RESUMO

Background: In China, childhood asthma prevalence showed a remarkable increase in the past decades. An updated epidemiological assessment of childhood asthma in China with a focus on prevalence and time trends is required. Methods: We systematically searched three main Chinese databases and one English database to identify epidemiological studies of the prevalence of childhood asthma in China. Asthma cases were defined according to one of the five sets of Chinese diagnostic criteria which were established by the Children Respiratory Disease Group. We estimated age- and sex-specific prevalence of asthma using a multilevel mixed-effects logistic regression. We presented the time trends of asthma prevalence between 1990 and 2020 by age, sex and setting (urban vs rural), and also estimated the number of children affected by asthma in 2010. Results: In 1990, the prevalence of asthma ranged from 0.13% (95% confidence interval (CI) = 0.10-0.20) in rural girls aged 14 years to 1.34% (95% CI = 1.11-1.67) in urban boys aged five years. In 2010, the overall prevalence of asthma in Chinese children aged 0-14 years was 2.12% (95% CI = 1.83-2.51), corresponding to 5.16 million children living with asthma. Children aged 5-9 years were with the highest prevalence estimate of 2.65% (95% CI = 2.31-3.12) and those aged 10-14 years were with the lowest (1.48%, 95% CI = 1.26-1.78). In 2020, it is expected that this disparity will continue, with the prevalence of asthma being at the lowest level among rural girls aged 14 years (1.11%, 95% CI = 0.82-1.54) and at the highest level among urban boys aged four years (10.27%, 95% CI = 8.61-12.18). Over the 30 years (1990-2020), the prevalence of asthma in children aged 0-14 years has increased in both sexes and settings, which was consistently the lowest in rural girls and the highest in urban boys. Conclusions: This study shows that childhood asthma has been increasingly prevalent in China. Asthma is more frequent in boys and in rural areas. The detailed and systematic estimates of asthma prevalence in this study constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources related to the burden of childhood asthma in China.


Assuntos
Asma/epidemiologia , Efeitos Psicossociais da Doença , Asma/psicologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prevalência , Qualidade de Vida , População Rural , Distribuição por Sexo , População Urbana
20.
J Infect Dis ; 222(Supplement_7): S680-S687, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32227101

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. METHODS: We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases. RESULTS: We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event. CONCLUSIONS: Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society.

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