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Norton S.,Kings College London | Matthews F.E.,Institute of Public Health | Barnes D.E.,University of California at San Francisco | Barnes D.E.,San Francisco Medical Center | And 3 more authors.
The Lancet Neurology

Background: Recent estimates suggesting that over half of Alzheimer's disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors. Methods: Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimer's disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050. Findings: Worldwide, the highest estimated PAR was for low educational attainment (19·1%, 95% CI 12·3-25·6). The highest estimated PAR was for physical inactivity in the USA (21·0%, 95% CI 5·8-36·6), Europe (20·3%, 5·6-35·6), and the UK (21·8%, 6·1-37·7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49·4% (95% CI 25·7-68·4), which equates to 16·8 million attributable cases (95% CI 8·7-23·2 million) of 33·9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28·2% (95% CI 14·2-41·5), which equates to 9·6 million attributable cases (95% CI 4·8-14·1 million) of 33·9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8·3% worldwide. Interpretation: After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression. Funding: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough. © 2014 Elsevier Ltd. Source

The burden of chronic conditions is high in low- and middle-income countries and poses a significant challenge to already weak healthcare delivery systems in these countries. Studies investigating chronic conditions among the urban poor remain few and focused on specific chronic conditions rather than providing overall profile of chronic conditions in a given community, which is critical for planning and managing services within local health systems. We aimed to assess the prevalence and health- seeking behaviour for self-reported chronic conditions in a poor neighbourhood of a metropolitan city in India. We conducted a house-to-house survey covering 9299 households (44514 individuals) using a structured questionnaire. We relied on self-report by respondents to assess presence of any chronic conditions, including diabetes and hypertension. Multivariable logistic regression was used to analyse the prevalence and health-seeking behaviour for self-reported chronic conditions in general as well as for diabetes and hypertension in particular. The predictor variables included age, sex, income, religion, household poverty status, presence of comorbid chronic conditions, and tiers in the local health care system. Overall, the prevalence of self-reported chronic conditions was 13.8% (95% CI = 13.4, 14.2) among adults, with hypertension (10%) and diabetes (6.4%) being the most commonly reported conditions. Older people and women were more likely to report chronic conditions. We found reversal of socioeconomic gradient with people living below the poverty line at significantly greater odds of reporting chronic conditions than people living above the poverty line (OR = 3, 95% CI = 1.5, 5.8). Private healthcare providers managed over 80% of patients. A majority of patients were managed at the clinic/health centre level (42.9%), followed by the referral hospital (38.9%) and the super-specialty hospital (18.2%) level. An increase in income was positively associated with the use of private facilities. However, elderly people, people below the poverty line, and those seeking care from hospitals were more likely to use government services. Our findings provide further evidence of the urgent need to improve care for chronic conditions for urban poor, with a preferential focus on improving service delivery in government health facilities. Source

Background:Although overall sociodemographic and cancer site variation in the risk of cancer diagnosis through emergency presentation has been previously described, relatively little is known about how this risk may vary differentially by sex, age and deprivation group between patients with a given cancer.Methods:Data from the Routes to Diagnosis project on 749 645 patients (2006–2010) with any of 27 cancers that can occur in either sex were analysed. Crude proportions and crude and adjusted odds ratios were calculated for emergency presentation, and interactions between sex, age and deprivation with cancer were examined.Results:The overall proportion of patients diagnosed through emergency presentation varied greatly by cancer. Compared with men, women were at greater risk for emergency presentation for bladder, brain, rectal, liver, stomach, colon and lung cancer (e.g., bladder cancer-specific odds ratio for women vs men, 1.50; 95% CI 1.39–1.60), whereas the opposite was true for oral/oropharyngeal cancer, lymphomas and melanoma (e.g., oropharyngeal cancer-specific odds ratio for women vs men, 0.49; 95% CI 0.32–0.73). Similarly, younger patients were at higher risk for emergency presentation for acute leukaemia, colon, stomach and oesophageal cancer (e.g., colon cancer-specific odds ratio in 35–44- vs 65–74-year-olds, 2.01; 95% CI 1.76–2.30) and older patients for laryngeal, melanoma, thyroid, oral and Hodgkin’s lymphoma (e.g., melanoma specific odds ratio in 35–44- vs 65–74-year-olds, 0.20; 95% CI 0.12–0.33). Inequalities in the risk of emergency presentation by deprivation group were greatest for oral/oropharyngeal, anal, laryngeal and small intestine cancers.Conclusions:Among patients with the same cancer, the risk for emergency presentation varies notably by sex, age and deprivation group. The findings suggest that, beyond tumour biology, diagnosis through an emergency route may be associated both with psychosocial processes, which can delay seeking of medical help, and with difficulties in suspecting the diagnosis of cancer after presentation.British Journal of Cancer advance online publication, 3 March 2015; doi:10.1038/bjc.2015.52 www.bjcancer.com. © 2015 Cancer Research UK Source

Benaglia T.,Medical Research Council | Sharples L.D.,Medical Research Council | Fitzgerald R.C.,Medical Research Council Cancer Cell Unit | Lyratzopoulos G.,Institute of Public Health

Background & Aims: We developed a model to compare the health benefits and cost effectiveness of screening for Barrett's esophagus by either Cytosponge™ or by conventional endoscopy vs no screening, and to estimate their abilities to reduce mortality from esophageal adenocarcinoma. Methods: We used microsimulation modeling of a hypothetical cohort of 50-year-old men in the United Kingdom with histories of gastroesophageal reflux disease symptoms, assuming the prevalence of Barrett's esophagus to be 8%. Participants were invited to undergo screening by endoscopy or Cytosponge (invitation acceptance rates of 23% and 45%, respectively), and outcomes were compared with those from men who underwent no screening. We estimated the number of incident esophageal adenocarcinoma cases prevented and the incremental cost-effectiveness ratio of quality-adjusted life years (QALYs) of the different strategies. Patients found to have high-grade dysplasia or intramucosal cancer received endotherapy. Model inputs included data on disease progression, test accuracy, post-treatment status, and surveillance protocols. Costs and benefits were discounted at 3.5% per year. Supplementary and sensitivity analyses comprised esophagectomy management of high-grade dysplasia or intramucosal cancer, screening by ultrathin nasal endoscopy, and different assumptions of uptake of screening invitations for either strategy. Results: We estimated that compared with no screening, Cytosponge screening followed by treatment of patients with dysplasia or intramucosal cancer costs an additional $240 (95% credible interval, $196-$320) per screening participant and results in a mean gain of 0.015 (95% credible interval, -0.001 to 0.029) QALYs and an incremental cost-effectiveness ratio of $15.7 thousand (K) per QALY. The respective values for endoscopy were $299 ($261-$367), 0.013 (0.003-0.023) QALYs, and $22.2K. Screening by the Cytosponge followed by treatment of patients with dysplasia or intramucosal cancer would reduce the number of cases of incident symptomatic esophageal adenocarcinoma by 19%, compared with 17% for screening by endoscopy, although this greater benefit for Cytosponge depends on more patients accepting screening by Cytosponge compared with screening by endoscopy. Conclusions: In a microsimulation model, screening 50-year-old men with symptoms of gastroesophageal reflux disease by Cytosponge is cost effective and would reduce mortality from esophageal adenocarcinoma compared with no screening. © 2013 AGA Institute. Source

Multiple imputation is often used for missing data. When a model contains as covariates more than one function of a variable, it is not obvious how best to impute missing values in these covariates. Consider a regression with outcome Y and covariates X and X2. In 'passive imputation' a value X* is imputed for X and then X2 is imputed as (X*)2. A recent proposal is to treat X2 as 'just another variable' (JAV) and impute X and X2 under multivariate normality. We use simulation to investigate the performance of three methods that can easily be implemented in standard software: 1) linear regression of X on Y to impute X then passive imputation of X2; 2) the same regression but with predictive mean matching (PMM); and 3) JAV. We also investigate the performance of analogous methods when the analysis involves an interaction, and study the theoretical properties of JAV. The application of the methods when complete or incomplete confounders are also present is illustrated using data from the EPIC Study. JAV gives consistent estimation when the analysis is linear regression with a quadratic or interaction term and X is missing completely at random. When X is missing at random, JAV may be biased, but this bias is generally less than for passive imputation and PMM. Coverage for JAV was usually good when bias was small. However, in some scenarios with a more pronounced quadratic effect, bias was large and coverage poor. When the analysis was logistic regression, JAV's performance was sometimes very poor. PMM generally improved on passive imputation, in terms of bias and coverage, but did not eliminate the bias. Given the current state of available software, JAV is the best of a set of imperfect imputation methods for linear regression with a quadratic or interaction effect, but should not be used for logistic regression. Source

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