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1.
PLoS Med ; 18(1): e1003498, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444330

RESUMO

BACKGROUND: Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. METHODS AND FINDINGS: Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009-0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40-75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation. CONCLUSIONS: Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Reino Unido/epidemiologia
2.
Diabetes Care ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203707

RESUMO

OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

3.
PLoS Med ; 17(10): e1003394, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33064751

RESUMO

BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

5.
Epidemiol Prev ; 44(5-6 Suppl 1): 179-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33415961

RESUMO

Barbara Pacelli, a young Italian epidemiologist, passed away unexpectedly in September 2019. During her prolific professional life, she gave several scientific contributions to natural disaster epidemiology, particularly in relation to the medium and long-term health effects of earthquakes. In this opinion paper, we reflect on Barbara's legacy and outline potential actions that could arise from her work. Particularly, availability of electronic health records would enable a systematic and large-scale investigation into the long-term health effects of earthquakes in Italy, a country with high seismic risk. This effort would have high societal value as it would likely enable mitigation of substantial morbidity and mortality in areas affected by earthquakes. In this paper, we define scope, objectives, potential data sources, and analysis methods that could be used to systematically assess the chronic health effects of recent earthquakes in Italy. Keywords: earthquakes; chronic diseases; electronic health records; retrospective cohort; case crossover study.

6.
Eur Respir J ; 53(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30923185

RESUMO

While traffic and air pollution exposure is associated with increased mortality in numerous diseases, its association with disease severity and outcomes in pulmonary arterial hypertension (PAH) remains unknown.Exposure to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2) and indirect measures of traffic-related air pollution (distance to main road and length of roads within buffer zones surrounding residential addresses) were estimated for 301 patients with idiopathic/heritable PAH recruited in the UK National Cohort Study of Idiopathic and Heritable PAH. Associations with transplant-free survival and pulmonary haemodynamic severity at baseline were assessed, adjusting for confounding variables defined a prioriHigher estimated exposure to PM2.5 was associated with higher risk of death or lung transplant (unadjusted hazard ratio (HR) 2.68 (95% CI 1.11-6.47) per 3 µg·m-3; p=0.028). This association remained similar when adjusted for potential confounding variables (HR 4.38 (95% CI 1.44-13.36) per 3 µg·m-3; p=0.009). No associations were found between NO2 exposure or other traffic pollution indicators and transplant-free survival. Conversely, indirect measures of exposure to traffic-related air pollution within the 500-1000 m buffer zones correlated with the European Society of Cardiology/European Respiratory Society risk categories as well as pulmonary haemodynamics at baseline. This association was strongest for pulmonary vascular resistance.In idiopathic/heritable PAH, indirect measures of exposure to traffic-related air pollution were associated with disease severity at baseline, whereas higher PM2.5 exposure may independently predict shorter transplant-free survival.


Assuntos
Poluição do Ar/efeitos adversos , Hipertensão Arterial Pulmonar/epidemiologia , Poluição Relacionada com o Tráfego/efeitos adversos , Adulto , Idoso , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Prospectivos , Hipertensão Arterial Pulmonar/etiologia , Poluição Relacionada com o Tráfego/análise , Reino Unido/epidemiologia
7.
JMIR Res Protoc ; 8(2): e10997, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30714576

RESUMO

BACKGROUND: Main causes of death in Greece are cardiovascular diseases (CVDs), malignant neoplasms, respiratory diseases, and road traffic crashes. To assess the population health status, monitor health systems, and adjust policies, national population-based health surveys are recommended. The previous health surveys that were conducted in Greece were restricted to specific regions or high-risk groups. OBJECTIVE: This paper presents the design and methods of the Greek Health Examination Survey EMENO (National Survey of Morbidity and Risk Factors). The primary objectives are to describe morbidity (focusing on CVD, respiratory diseases, and diabetes), related risk factors, as well as health care and preventive measures utility patterns in a random sample of adults living in Greece. METHODS: The sample was selected by applying multistage stratified random sampling on 2011 Census. Trained interviewers and physicians made home visits. Standardized questionnaires were administered; physical examination, anthropometric and blood pressure measurements, and spirometry were performed. Blood samples were collected for lipid profile, glucose, glycated hemoglobin, and transaminases measurements. The survey was conducted from May 2013 until June 2016. RESULTS: In total, 6006 individuals were recruited (response rate 72%). Of these, 4827 participated in at least one physical examination, 4446 had blood tests, and 3622 spirometry, whereas 3580 provided consent for using stored samples for future research (3528 including DNA studies). Statistical analysis has started, and first results are expected to be submitted for publication by the end of 2018. CONCLUSIONS: EMENO comprises a unique health data resource and a bio-resource in a Mediterranean population. Its results will provide valid estimates of morbidity and risk factors' prevalence (overall and in specific subdomains) and health care and preventive measures usage in Greece, necessary for an evidence-based strategy planning of health policies and preventive activities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10997.

8.
Nat Commun ; 9(1): 260, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343764

RESUMO

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Proteínas de Transporte Vesicular/genética , Vitamina D/análogos & derivados , Amidoidrolases/genética , Doenças Autoimunes/genética , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Vitamina D/sangue
9.
Am J Epidemiol ; 186(1): 101-108, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453604

RESUMO

Many measures of chronic diseases, including respiratory disease, exhibit seasonal variation together with residual correlation between consecutive time periods and neighboring areas. We demonstrate a strategy for modeling data that exhibit both seasonal trend and spatiotemporal correlation, using an application to respiratory prescribing. We analyzed 55 months (2002-2006) of prescribing data from the northeast of England, in the United Kingdom. We estimated the seasonal pattern of prescribing by fitting a dynamic harmonic regression (DHR) model to salbutamol prescribing in relation to temperature. We compared the output of DHR models to static sinusoidal regression models. We used the DHR-fitted values as an offset in mixed-effects models that aimed to account for the remaining spatiotemporal variation in prescribing rates. As diagnostic checks, we assessed spatial and temporal correlation separately and jointly. Our application of a DHR model resulted in a better fit to the seasonal variation of prescribing than was obtained with a static model. After adjusting for the fitted values from the DHR model, we did not detect any remaining spatiotemporal correlation in the model's residuals. Using a DHR model and temperature data to account for the periodicity of prescribing proved to be an efficient way to capture its seasonal variation. The diagnostic procedures indicated that there was no need to model any remaining correlation explicitly.


Assuntos
Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Uso de Medicamentos/estatística & dados numéricos , Vigilância em Saúde Pública/métodos , Estações do Ano , Análise Espaço-Temporal , Distribuição por Idade , Poluição do Ar/estatística & dados numéricos , Asma/tratamento farmacológico , Asma/epidemiologia , Doença Crônica , Inglaterra , Humanos , Modelos Estatísticos , Padrões de Prática Médica , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Análise de Regressão , Doenças Respiratórias , Distribuição por Sexo , Fatores Socioeconômicos
10.
Lancet ; 388(10046): 776-86, 2016 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-27423262

RESUMO

BACKGROUND: Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant data meta-analyses of prospective studies of body-mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding pre-existing disease and the first 5 years of follow-up. METHODS: Of 10 625 411 participants in Asia, Australia and New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 years, IQR 11·4-14·7), 3 951 455 people in 189 studies were never-smokers without chronic diseases at recruitment who survived 5 years, of whom 385 879 died. The primary analyses are of these deaths, and study, age, and sex adjusted hazard ratios (HRs), relative to BMI 22·5-<25·0 kg/m(2). FINDINGS: All-cause mortality was minimal at 20·0-25·0 kg/m(2) (HR 1·00, 95% CI 0·98-1·02 for BMI 20·0-<22·5 kg/m(2); 1·00, 0·99-1·01 for BMI 22·5-<25·0 kg/m(2)), and increased significantly both just below this range (1·13, 1·09-1·17 for BMI 18·5-<20·0 kg/m(2); 1·51, 1·43-1·59 for BMI 15·0-<18·5) and throughout the overweight range (1·07, 1·07-1·08 for BMI 25·0-<27·5 kg/m(2); 1·20, 1·18-1·22 for BMI 27·5-<30·0 kg/m(2)). The HR for obesity grade 1 (BMI 30·0-<35·0 kg/m(2)) was 1·45, 95% CI 1·41-1·48; the HR for obesity grade 2 (35·0-<40·0 kg/m(2)) was 1·94, 1·87-2·01; and the HR for obesity grade 3 (40·0-<60·0 kg/m(2)) was 2·76, 2·60-2·92. For BMI over 25·0 kg/m(2), mortality increased approximately log-linearly with BMI; the HR per 5 kg/m(2) units higher BMI was 1·39 (1·34-1·43) in Europe, 1·29 (1·26-1·32) in North America, 1·39 (1·34-1·44) in east Asia, and 1·31 (1·27-1·35) in Australia and New Zealand. This HR per 5 kg/m(2) units higher BMI (for BMI over 25 kg/m(2)) was greater in younger than older people (1·52, 95% CI 1·47-1·56, for BMI measured at 35-49 years vs 1·21, 1·17-1·25, for BMI measured at 70-89 years; pheterogeneity<0·0001), greater in men than women (1·51, 1·46-1·56, vs 1·30, 1·26-1·33; pheterogeneity<0·0001), but similar in studies with self-reported and measured BMI. INTERPRETATION: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This finding supports strategies to combat the entire spectrum of excess adiposity in many populations. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, US National Institutes of Health.


Assuntos
Índice de Massa Corporal , Causas de Morte , Mortalidade/tendências , Adulto , Idoso , Ásia/epidemiologia , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , América do Norte/epidemiologia , Sobrepeso/mortalidade , Estudos Prospectivos
11.
Endoscopy ; 47(3): 225-31, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25268309

RESUMO

BACKGROUND AND STUDY AIMS: Following the results of a major UK study showing that once-only flexible sigmoidoscopy (FSIG) screening significantly reduced colorectal cancer (CRC) incidence and mortality, an FSIG screening program in England was announced in late 2010. Three "early pilot" sites were selected in 2011 in Derby, South of Tyne, and Tees to assess the practicalities of the delivery of FSIG screening. PARTICIPANTS AND METHODS: Eligible people aged 55 from selected practices in the three early pilot areas received postal invitations to participate. The South of Tyne and Derby sites employed interactive models of screening invitation, while Tees used a simple invitation. Data were collected to assess uptake, process, and outcome. A self-completion participant satisfaction questionnaire was sent to all participants 1 month after attendance. RESULTS: A total of 4023 55-year-olds were invited to participate. Uptake was 29 %, with 1151 people screened over a 3-month period. Screening uptake differed by method of invitation: a simple approach was significantly more successful than an interactive one (32 % vs. 27 %, P = 0.0015). Uptake decreased significantly with increasing deprivation. Adenomas were found in 111 (9.8 %) of those screened and cancer in two. The procedure was rated "very" or "fairly" acceptable by 97 % of participants. Over 90 % of respondents said they would participate in future cancer screening and a similar proportion would recommend doing so to others. CONCLUSION: Delivery of an FSIG screening program to prevent CRC is feasible and should be implemented using a simple invitation system. The national Bowel Scope program subsequently commenced at pilot sites in May 2013, with full implementation planned by 2016.


Assuntos
Adenoma/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Seleção de Pacientes , Desenvolvimento de Programas/métodos , Neoplasias Retais/diagnóstico , Neoplasias do Colo Sigmoide/diagnóstico , Sigmoidoscopia , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Projetos Piloto , Estudos Prospectivos , Fatores Socioeconômicos , Inquéritos e Questionários
12.
J Public Health (Oxf) ; 35(4): 502-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24293452

RESUMO

BACKGROUND: We investigated the association between respiratory prescribing, air quality and deprivation in primary health care. Most previous studies have used data from secondary and tertiary care to quantify air pollution effects on exacerbations of asthma and chronic obstructive pulmonary disease (COPD). However, these outcomes capture patients who suffer from relatively severe symptoms. METHODS: This is a population-based ecological study. We analysed respiratory medication (salbutamol) prescribed monthly by 63 primary care practices, UK. Firstly, we captured the area-wide seasonal variation in prescribing. Then, using the area-wide variation in prescribing as an offset, we built a mixed-effects model to assess the remaining variation in relation to air quality and demographic variables. RESULTS: An increase of 10 µg/m(3) in ambient PM10 was associated with an increase of 1% (95% CI: 0.1-2%) in salbutamol prescribing. An increase of 1 SD in income and employment deprivation was associated with an increase of 20.5% (95% CI: 8.8-33.4%) and 14.7% (95% CI: 4.3-26.2%) in salbutamol prescribing rate, respectively. CONCLUSIONS: The study provides evidence that monthly respiratory prescribing in primary care is a useful indicator of the extent to which air pollution exacerbates asthma and COPD symptoms. Respiratory prescribing was higher on deprived populations.


Assuntos
Poluição do Ar/efeitos adversos , Albuterol/uso terapêutico , Broncodilatadores/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Pobreza/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Poluição do Ar/estatística & dados numéricos , Asma/tratamento farmacológico , Asma/epidemiologia , Feminino , Humanos , Masculino , Material Particulado/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estações do Ano , Fatores Socioeconômicos , Reino Unido/epidemiologia , Adulto Jovem
13.
Health Place ; 18(6): 1248-54, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23041911

RESUMO

Where patients who are registered with a general practice actually live (the service utilisation area) often differ from what GPs consider their practice boundaries or catchment area to be, as well as from administrative boundaries. A key aim of primary care commissioners is to allocate resources efficiently and to locate services in such a way that access is convenient for patients. To achieve this robust understanding of practice service utilisation areas and the overlap between practices and administrative areas are essential. We used kernel analysis of the postcodes of over 400,000 registered patients to define GP service utilisation areas. We estimated service utilisation for each of 64 practices for a period of five years (2002-2006) exploring the areas in which 99%, 98%, and 95% of registered patients were expected to live. These service utilisation areas were not coterminous with other practices or with administrative boundaries. We present a simple analytical method to define GP catchment areas that captures the true service utilisation area and identifies the extent of overlap. This is a practical tool that can assist health care commissioning.


Assuntos
Área Programática de Saúde/estatística & dados numéricos , Medicina Geral/estatística & dados numéricos , Inglaterra/epidemiologia , Clínicos Gerais/estatística & dados numéricos , Política de Saúde , Humanos , Densidade Demográfica
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