[Show abstract][Hide abstract] ABSTRACT: AbstracObjectives
To examine the prevalence of seizures, epilepsy, and seropositivity to cysticercosis in rural villagers (cysticercosis-endemic setting), rural-to-urban migrants into a non-endemic urban shantytown, and urban inhabitants of the same non-endemic shanty town.Methods
Three Peruvian populations (n=985) originally recruited into a study about chronic diseases and migration, were studied. These groups included rural inhabitants from an endemic region (n=200), long-term rural-to-urban migrants (n=589), and individuals living in the same urban setting (n=196). Seizure disorders were detected by a survey and a neurologist examined positive respondents. Serum samples from 981/985 individuals were processed for cysticercosis antibodies on immunoblot.ResultsEpilepsy prevalence (per 1,000 people) was 15.3 in the urban group, 35.6 in migrants, and 25 in rural inhabitants. A gradient in cysticercosis antibody seroprevalence was observed: urban 2%, migrant 13.5%, and rural group 18% (p<0.05). A similarly increasing pattern of higher seroprevalence was observed among migrants by age at migration. In rural villagers, there was strong evidence of an association between positive serology and having seizures (p=0.011) but such an association was not observed in long-term migrants or in urban residents. In the entire study population, compared to seronegative participants, those with strong antibody reactions (≥4 antibody bands) were more likely to have epilepsy (p<0.001).Conclusions
It is not only international migration that affects cysticercosis endemicity; internal migration can also affect patterns of endemicity within an endemic country. The neurologic consequences of cysticercosis infection likely outlast the antibody response for years after rural-to-urban migration.This article is protected by copyright. All rights reserved.
Tropical Medicine & International Health 01/2015; · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsDrug treatments for obesity have proven efficacy from randomised trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.Methods
We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over three years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95 % confidence intervals (CI) was estimated.ResultsWe identified 100,701 patients receiving orlistat, 15,355 receiving sibutramine and 508,140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg/m2 respectively. Patients receiving orlistat lost, on average, 0.94 kg/month (0.93 to 0.95) over the first four months. Weight gain then occurred, although weight remained slightly below baseline at three years. Patients receiving sibutramine lost, 1.28 kg/month (1.26 to 1.30) over the first four months, but by three years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the three-year period, with gains ranging between 0.01 and 0.06 kg/month..Conclusions
Orlistat and sibutramine had early effects on weight loss, not sustained over three years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomised trials.
British Journal of Clinical Pharmacology 12/2014; · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to evaluate the performance of risk scores (Framingham, Assign and QRISK2) in predicting high cardiovascular disease (CVD) risk in individuals rather than populations.
PLoS ONE 10/2014; 9(10):e106455. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsThis was a cohort study to evaluate if individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors.Methods
The study included new users of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year.ResultsA total of 426,089 persons were included in the primary analysis, with 45,541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin-converting enzyme inhibitors. The total number of new diagnoses of dementia was 6,517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after start of treatment (adjusted hazard ratio 0.92, 95% CI 0.85-1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% CI 0.50-0.72).ConclusionsA small reduction in dementia risk was seen with angiotensin receptor blockers compared with angiotensin-converting enzyme inhibitors. However the strongest association was seen in early follow-up suggesting the inverse association is unlikely to be causal, but reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users.
British Journal of Clinical Pharmacology 09/2014; · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers.
With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects.
5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI.
BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups.
National Institute for Health Research, Wellcome Trust, and Medical Research Council.
[Show abstract][Hide abstract] ABSTRACT: Ischaemia in different arterial territories before acute myocardial infarction (AMI) may influence post-AMI outcomes. No studies have evaluated prospectively collected information on ischaemia and its effect on short- and long-term coronary mortality. The objective of this study was to compare patients with and without prospectively measured ischaemic presentations before AMI in terms of infarct characteristics and coronary mortality.
European Heart Journal 07/2014; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To inform potential pathophysiological mechanisms of air pollution effects on cardiovascular disease (CVD), we investigated short-term associations between ambient air pollution and a range of cardiovascular events from three national databases in England and Wales.
[Show abstract][Hide abstract] ABSTRACT: There is strong evidence of reductions in major vascular events from statins across all cardiovascular risk categories. However, trials of statin therapy have provided conflicting results regarding statin use and type 2 diabetes (T2DM). We aimed to assess the effect of statins on T2DM development.
[Show abstract][Hide abstract] ABSTRACT: Antipsychotics increase the risk of stroke. Their effect on myocardial infarction remains uncertain because people prescribed and not prescribed antipsychotic drugs differ in their underlying vascular risk making between-person comparisons difficult to interpret. The aim of our study was to investigate this association using the self-controlled case series design that eliminates between-person confounding effects.
European Heart Journal 07/2014; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.
BMJ Open 07/2014; 4(7):e005540. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic and hypnotic drugs taken in the first trimester of pregnancy, compared with children of mothers with depression and/or anxiety but not treated with medication and children of mothers without diagnosed mental illness during pregnancy.
PLoS ONE 06/2014; 9(6):e100996. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our understanding of genome biology, genomics, and disease, and even hu-man history, has advanced tremen-dously with the completion of the Human Genome Project. Technologi-cal advances coupled with significant cost reductions in genomic research have yielded novel insights into disease etiol-ogy, diagnosis, and therapy for some of the world's most intractable and devastat-ing diseases—including ma-laria, HIV/AIDS, tuberculosis, cancer, and diabetes. Yet, de-spite the burden of infectious diseases and, more recently, noncommunicable diseases (NCDs) in Africa, Africans have only par-ticipated minimally in genomics research. Of the thousands of genome-wide association studies (GWASs) that have been conducted globally, only seven (for HIV susceptibility, malaria, tuberculosis, and podoconiosis) have been conducted exclusively on Afri-can participants; four others (for prostate cancer, obsessive compulsive disorder, and anthropometry) included some African participants (www.genome.gov/gwastudies/). As discussed in 2011 (www.h3africa.org), if the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent. The lack of large-scale genomics studies in Africa is the result of many deep-seated issues, including a shortage of African scien-tists with genomic research expertise, lack of biomedical research infrastructure, lim-ited computational expertise and resources, lack of adequate support for biomedical research by African governments, and the participation of many African scientists in collaborative research at no more than the level of sample collection. Overcoming these limitations will, in part, depend on African Enabling the genomic revolution in Africa By The H3Africa Consortium * H3Africa is developing capacity for health-related genomics research in Africa Yet, roughly a decade ago, newly pro-posed DNA-based taxonomy (11) promised to solve the species debate. A Barcode of Life Data Systems (BOLD) (12) quickly emerged, seeking to provide a reliable, cost-effective solution to the problem of species identification (12) and a standard screening threshold of sequence differ-ence (10× average intraspecific difference) to speed the discovery of new animal spe-cies (13). Sometimes considered a "carica-ture of real taxonomy" (14), this approach failed to identify, perhaps not surprisingly, two American crow species and a number of members of the herring gull Larus ar-gentatus species assemblage above the set threshold (13). Furthermore, despite past (3) and present (6) sequencing projects, carrion crows and hooded crows can also not be differentiated from one another by means of DNA-barcode approaches. By contrast, Poelstra et al. show that much more DNA sequencing data are needed, combined with RNA expression data, to reconstruct the evolution of a reproductive barrier that culminated in the speciation of these two crow taxa. Armed with this new very detailed genetic informa-tion, it is clear that none of the currently formulated species concepts fully apply to these two crow taxa (unless one is willing relax some stringency in the various definitions). In-deed, the genomes of German carrion crows are much more similar to those of hooded crows than to Spanish car-rion crows. Put simply, apart from the few carrion crow type "speciation islands," German carrion crows could be con-sidered to represent hooded crows with a black (carrion crow) phenotype. There is a clear need for ad-ditional population genomic studies using a more dense sampling, especially among the fully black carrion crows, before the complexity of repro-ductive isolation and speciation among these two taxa can be fully understood. The specia-tion genomics strategy already proved itself in unraveling the complexities of mimicry among many Heliconius butterfly taxa (7) and, as in the study of Poelstra et al., stresses the im-portance of using RNA-based information in addition to DNA. Only time will tell if, and when, German carrion crows will adopt the "hooded phenotype," a fate that seems un-avoidable. Until then, we can only applaud these crows for defeating Linnaeus's curse.
[Show abstract][Hide abstract] ABSTRACT: The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.
The Lancet 05/2014; 383(9932):1899-911. · 39.21 Impact Factor