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1.  Angiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink 
Aims
This was a cohort study to evaluate whether 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.
Results
A 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 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 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% confidence interval 0.50–0.72).
Conclusions
A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users.
doi:10.1111/bcp.12511
PMCID: PMC4309639  PMID: 25223602
angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; dementia
2.  A systematic review and meta-analysis of risk factors for postherpetic neuralgia 
Pain  2015;157(1):30-54.
Supplemental Digital Content is Available in the Text.
Abstract
Patients with herpes zoster can develop persistent pain after rash healing, a complication known as postherpetic neuralgia. By preventing zoster through vaccination, the risk of this common complication is reduced. We searched MEDLINE and Embase for studies assessing risk factors for postherpetic neuralgia, with a view to informing vaccination policy. Nineteen prospective studies were identified. Meta-analysis showed significant increases in the risk of postherpetic neuralgia with clinical features of acute zoster including prodromal pain (summary rate ratio 2.29, 95% confidence interval: 1.42-3.69), severe acute pain (2.23, 1.71-2.92), severe rash (2.63, 1.89-3.66), and ophthalmic involvement (2.51, 1.29-4.86). Older age was significantly associated with postherpetic neuralgia; for individual studies, relative risk estimates per 10-year increase ranged from 1.22 to 3.11. Evidence for differences by gender was conflicting, with considerable between-study heterogeneity. A proportion of studies reported an increased risk of postherpetic neuralgia with severe immunosuppression (studies, n = 3/5) and diabetes mellitus (n = 1/4). Systemic lupus erythematosus, recent trauma, and personality disorder symptoms were associated with postherpetic neuralgia in single studies. No evidence of higher postherpetic neuralgia risk was found with depression (n = 4) or cancer (n = 5). Our review confirms a number of clinical features of acute zoster are risk factors for postherpetic neuralgia. It has also identified a range of possible vaccine-targetable risk factors for postherpetic neuralgia; yet aside from age-associated risks, evidence regarding risk factors to inform zoster vaccination policy is currently limited.
doi:10.1097/j.pain.0000000000000307
PMCID: PMC4685754  PMID: 26218719
Herpes zoster; Postherpetic neuralgia; Epidemiology; Risk factors
3.  Bariatric Surgery in the United Kingdom: A Cohort Study of Weight Loss and Clinical Outcomes in Routine Clinical Care 
PLoS Medicine  2015;12(12):e1001925.
Background
Bariatric surgery is becoming a more widespread treatment for obesity. Comprehensive evidence of the long-term effects of contemporary surgery on a broad range of clinical outcomes in large populations treated in routine clinical practice is lacking. The objective of this study was to measure the association between bariatric surgery, weight, body mass index, and obesity-related co-morbidities.
Methods and Findings
This was an observational retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. All 3,882 patients registered in the database and with bariatric surgery on or before 31 December 2014 were included and matched by propensity score to 3,882 obese patients without surgery. The main outcome measures were change in weight and body mass index over 4 y; incident diagnoses of type 2 diabetes mellitus (T2DM), hypertension, angina, myocardial infarction (MI), stroke, fractures, obstructive sleep apnoea, and cancer; mortality; and resolution of hypertension and T2DM. Weight measures were available for 3,847 patients between 1 and 4 mo, 2,884 patients between 5 and 12 mo, and 2,258 patients between 13 and 48 mo post-procedure. Bariatric surgery patients exhibited rapid weight loss for the first four postoperative months, at a rate of 4.98 kg/mo (95% CI 4.88–5.08). Slower weight loss was sustained to the end of 4 y. Gastric bypass (6.56 kg/mo) and sleeve gastrectomy (6.29 kg/mo) were associated with greater initial weight reduction than gastric banding (2.77 kg/mo). Protective hazard ratios (HRs) were detected for bariatric surgery for incident T2DM, 0.68 (95% CI 0.55–0.83); hypertension, 0.35 (95% CI 0.27–0.45); angina, 0.59 (95% CI 0.40–0.87);MI, 0.28 (95% CI 0.10–0.74); and obstructive sleep apnoea, 0.55 (95% CI 0.40–0.87). Strong associations were found between bariatric surgery and the resolution of T2DM, with a HR of 9.29 (95% CI 6.84–12.62), and between bariatric surgery and the resolution of hypertension, with a HR of 5.64 (95% CI 2.65–11.99). No association was detected between bariatric surgery and fractures, cancer, or stroke. Effect estimates for mortality found no protective association with bariatric surgery overall, with a HR of 0.97 (95% CI 0.66–1.43). The data used were recorded for the management of patients in primary care and may be subject to inaccuracy, which would tend to lead to underestimates of true relative effect sizes.
Conclusions
Bariatric surgery as delivered in the UK healthcare system is associated with dramatic weight loss, sustained at least 4 y after surgery. This weight loss is accompanied by substantial improvements in pre-existing T2DM and hypertension, as well as a reduced risk of incident T2DM, hypertension, angina, MI, and obstructive sleep apnoea. Widening the availability of bariatric surgery could lead to substantial health benefits for many people who are morbidly obese.
In a UK cohort study, Ian Douglas and colleagues investigate weight, BMI, and related health outcomes after bariatric surgery.
Editors' Summary
Background
Obesity—having an unhealthy amount of body fat—is a growing threat to global public health. Worldwide, 13% of adults are obese, and, in the UK and the US, the statistics are even worse. A quarter and a third, respectively, of adults in these countries are obese. Obesity is defined as having a body mass index (BMI; an indicator of body fat calculated by dividing a person’s weight in kilograms by their height in meters squared) of ≥30 kg/m2. Compared to people with a healthy weight (a BMI of 18.5–24.9 kg/m2), overweight and obese people have an increased risk of developing type 2 diabetes, cardiovascular conditions such as hypertension (high blood pressure), myocardial infarction (heart attack), angina, and stroke, and they tend to die younger. People become overweight, and eventually obese, by consuming food and drink that contain more energy (calories) than they need for their daily activities. So, obesity can be prevented and reversed by eating less and exercising more.
Why Was This Study Done?
People with severe obesity (BMI of 40 kg/m2 or more) who have tried but failed to control their weight through lifestyle changes sometimes undergo bariatric surgery (weight loss surgery). In the UK and the US, this approach is also recommended for obese individuals who have an obesity-related illness such as type 2 diabetes with a lower BMI of 35 kg/m2 or more. Techniques such as gastric band surgery, gastric bypass, and sleeve gastrectomy all lead to reduced energy intake, and in randomized controlled trials comparing bariatric surgery and lifestyle interventions, bariatric surgery is associated with greater weight loss. However, the results of clinical trials are not always replicated in routine clinical practice. Here, the researchers investigate whether there is an association between bariatric surgery and weight, BMI, and obesity-related co-morbidities (illnesses) in the UK by undertaking a retrospective cohort study (an observational study that compares recorded clinical outcomes in non-randomized groups of patients who received different treatments).
What Did the Researchers Do and Find?
The researchers used the UK Clinical Practice Research Datalink, which contains anonymized clinical information about patients provided by general practitioners (primary care physicians), to identify 3,882 patients who had had bariatric surgery. They matched each patient (average BMI 44.7 kg/m2), according to the patient’s medications and constellation of risk factors, to an obese individual from the dataset who had not had bariatric surgery. This “propensity matching” technique is used in studies where patients are not allocated at random to receive a treatment, and is meant to control for confounding—the possibility that patients who receive the treatment may be otherwise distinct from patients who do not. According to this analysis, patients who had had bariatric surgery lost weight rapidly during the first four post-operative months (4.98 kg/month); their weight loss was sustained at a slower rate for up to four years. By contrast, there were no weight changes in the patients who did not have surgery. Notably, bariatric surgery was associated with a lower risk of type 2 diabetes onset, hypertension onset, angina onset, myocardial infarction, and obstructive sleep apnea (a sleep disorder) onset, and with the resolution of both type 2 diabetes and hypertension in those who already had these conditions when they underwent surgery. However, over an average of 3.4 years of follow-up, there was no evidence of any difference in the risk of death.
What Do These Findings Mean?
These findings show that bariatric surgery delivered in routine clinical practice in the UK is associated with a substantial initial weight loss that is sustained for at least four years after surgery. They also show that bariatric surgery is associated with improvements in pre-existing type 2 diabetes and hypertension and with a reduced risk of developing several obesity-related co-morbidities. Because the data used in the study were recorded for patient management by primary care physicians, the researchers were unable to use strict diagnostic criteria for some outcomes, which may limit the accuracy of these findings. Nevertheless, these results suggest that widening the availability of bariatric surgery in the UK could provide substantial health benefits for many people who are morbidly obese. Indeed, the researchers calculate that, if the associations seen in this study are causal (an observational study cannot prove that a treatment causes a specific outcome), bariatric surgery could prevent and/or resolve many tens of thousands of cases of hypertension and type 2 diabetes and prevent similar numbers of cases of other obesity-related illnesses among the 1.4 million morbidly obese people living in the UK.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001925.
The World Health Organization provides information on obesity (in several languages)
The Institute for Health Metrics and Evaluation website provides the latest details about global obesity trends; the World Obesity Federation also provides information about the global obesity epidemic
The UK National Health Service Choices website provides information about obesity (including some real stories), bariatric surgery (including some comments from patients), and healthy eating
The US Centers for Disease Control and Prevention has information on all aspects of overweight and obesity
ChooseMyPlate.gov is a resource provided by the US Department of Agriculture that provides individuals and healthcare professionals with user-friendly information on nutrition and physical exercise
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information on bariatric surgery and on weight control and healthy living
MedlinePlus provides links to other sources of information on obesity and bariatric surgery (in English and Spanish)
doi:10.1371/journal.pmed.1001925
PMCID: PMC4687869  PMID: 26694640
4.  Risk factors of hypertension among adults aged 35–64 years living in an urban slum Nairobi, Kenya 
BMC Public Health  2015;15:1251.
Background
Hypertension is an emerging public health problem in Sub Saharan Africa (SSA) and urbanization is considered to favor its emergence. Given a paucity of information on hypertension and associated risk factors among urban slum dwellers in SSA, we aimed to characterize the distribution of risk factors for hypertension and investigate their association with hypertension in an urban slum in Kenya.
Methods
We conducted a community based cross-sectional survey among adults 35 years and older living in Kibera slum Nairobi, Kenya. Trained interviewers collected data on socio demographic characteristics and self reported health behaviours using modified World Health Organization stepwise surveillance questionnaire for chronic disease risk factors. Anthropometric and blood pressure measurements were performed following standard procedures. Multiple logistic regression was used for analysis and odds ratios with 95 % confidence intervals were calculated to identify risk factors associated with hypertension.
Result
A total of 1528 adults were surveyed with a mean age of 46.7 years. The age-standardized prevalence of hypertension was 29.4 % (95 % CI 27.0–31.7). Among the 418 participants classified as hypertensive, over one third (39.0 %) were unaware they had hypertension. Prevalence of current smoking and alcohol consumption was 8.5 and 13.1 % respectively. Over one quarter 26.2 % participants were classified as overweight (Body Mass Index [BMI] ≥25 to ≤29.9 kg/m2), and 17 % classified as obese (BMI ≥30 kg/m2). Overweight, obesity, current smoking, some level of education, highest wealth index, moderate physical activity, older age and being widowed were each independently associated with hypertension. When fit in a multivariable logistic regression model, being a widow [AOR = 1.7; (95 % CI, 1.1–2.6)], belonging to the highest wealth index [AOR = 1.6; (95 % CI, 1.1–2.5)], obesity [AOR = 1.8; 95 % CI, 1.1–3.1)] and moderate physical activity [AOR = 1.9; (95 % CI, 1.2–3.0)], all remained significantly associated with hypertension.
Conclusion
Hypertension in the slum is a public health problem affecting at least one in three adults aged 35–64 years. Age, marital status, wealth index, physical inactivity and body mass index are important risk factors associated with hypertension. Prevention measures targeting the modifiable risk factors associated with hypertension are warranted to curb hypertension and its progressive effects.
doi:10.1186/s12889-015-2610-8
PMCID: PMC4683777  PMID: 26679701
Hypertension; Risk factors; Urbanization; Obesity; Cardiovascular diseases
5.  Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States 
PLoS Medicine  2015;12(12):e1001919.
Background
Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association.
Methods and Findings
The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17–2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47–1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75–1.74) and unvaccinated (IR 1.78, 95% CI 1.68–1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study’s power to assess the role of vaccination.
Conclusions
Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events.
Using U.S. Medicare data, Caroline Minassian and colleagues test for associations between shingles and subsequent myocardial infarction or stroke.
Editors' Summary
Background
Chickenpox, which is caused by the varicella zoster virus, is a common childhood infectious disease. Although recovery from chickenpox is usually quick, the varicella zoster virus can persist throughout life inside the nervous system. The dormant virus causes no symptoms, but if it becomes activated, it causes herpes zoster (also known as shingles or zoster), a painful skin rash. Anyone who has had chickenpox can develop zoster, but the condition is most common and most severe in elderly people—half of zoster episodes occur in people aged more than 60 years. Early signs of zoster include burning or shooting pain, tingling, and itching. Blister-like sores, which last 1–14 days, then develop on one side of the face or on one side of the body in a horizontal band. The pain of zoster, which can be debilitating, can continue for years after the rash disappears—a condition called post-herpetic neuralgia, which greatly reduces the quality of life. There is no cure for zoster, but vaccination can prevent the condition or lessen its effects, and early treatment with antivirals may prevent lingering pain by inhibiting viral replication.
Why Was This Study Done?
Association studies suggest that people have an increased risk of an acute cardiovascular event—a stroke or a myocardial infarction (MI; heart attack)—in the weeks and months following a zoster episode. However, these studies mainly compared the incidence of stroke and MI (the number of strokes and MIs in a given time period) among people who had had zoster with the incidence among people who had not had zoster and were therefore vulnerable to between-person confounding. That is, rather than zoster increasing a person’s risk of MI or stroke, people who had had zoster may have shared another unknown characteristic (confounder) that was responsible for their increased risk of MI and stroke. Here, the researchers investigate whether there is an increased risk of acute cardiovascular events after zoster using a self-controlled case series study design. Specifically, they compare the incidence of MI and ischemic stroke in a population of individuals during a period of time before and more than a year after the individuals had zoster with the incidence of MI and ischemic stroke in the same individuals during the weeks and months right after they were diagnosed with zoster. Because each case is his/her own control, between-person confounding is avoided.
What Did the Researchers Do and Find?
The researchers identified 42,954 Medicare beneficiaries aged ≥65 years who had had a zoster diagnosis and an ischemic stroke and 24,237 beneficiaries who had had a zoster diagnosis and an MI during a five-year period (Medicare is a US government health insurance plan that mainly covers the healthcare costs of elderly individuals; an ischemic stroke occurs when a blood clot blocks the brain’s blood supply). They then calculated age-adjusted incidence ratios for stroke and MI during predefined periods up to 12 months after a diagnosis of zoster relative to the time period before and more than a year after a diagnosis of zoster (the “baseline” period). Compared to the baseline period, there was a 2.4-fold increased rate of ischemic stroke and a 1.7-fold increased rate of MI in the first week after zoster. The increased rate of acute cardiovascular events reduced gradually over the six months following zoster. There was no evidence that MI or ischemic stroke incidence ratios differed between individuals who had been vaccinated against zoster (but still contracted the disease) and those who had not been vaccinated.
What Do These Findings Mean?
These findings suggest that zoster is associated with transiently increased rates of ischemic stroke and MI. Zoster vaccination—which reduces zoster incidence by half and can reduce zoster symptoms—was not found to modify the associations between zoster and ischemic stroke or MI. However, this second finding needs confirmation: the study had limited power to detect an effect of vaccination on ischemic stroke or MI following zoster, given the small number of participants who were vaccinated and then developed zoster despite being vaccinated. Another potential study limitation is residual confounding. Although the self-controlled case series design controls for time-fixed confounders, time-varying factors such as major life events or stress may still play a role in the association. Thus, an episode of zoster may cause stress, which could then lead to an increased risk of MI or stroke. Importantly, however, these findings enhance our understanding of the magnitude and timing of the association between zoster and acute cardiovascular events and provide information that might help to prevent such events in older individuals.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001919.
The US Centers for Disease Control and Prevention has detailed information about all aspects of shingles (zoster), including information on vaccination, and information on stroke and myocardial infarction
The National Institutes of Health Senior Health website includes information on zoster, a video describing a personal experience of zoster, and information on stroke and heart attack
The UK National Health Service Choices website provides information about all aspects of zoster and about cardiovascular disease
MedlinePlus provides links to other resources about zoster, stroke, and heart attack (in English and Spanish)
doi:10.1371/journal.pmed.1001919
PMCID: PMC4682931  PMID: 26671338
6.  Seizures, cysticercosis and rural-to-urban migration: the PERU MIGRANT study 
Objectives
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 shanty town 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.
Results
Epilepsy prevalence (per 1000 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 with 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 neurological consequences of cysticercosis infection likely outlast the antibody response for years after rural-to-urban migration.
Objectifs
Examiner la prévalence des crises d’épilepsie, de l’épilepsie et de la séropositivité à la cysticercose chez les villageois des zones rurales (cadre endémique pour la cysticercose), chez les migrants des zones ruraux vers les zones urbaines dans un bidonville urbain non endémique et chez les habitants urbains du même bidonville non endémique.
Méthodes
Trois populations péruviennes (n = 985) recrutées initialement dans une étude sur les maladies chroniques et la migration, ont été étudiées. Ces groupes comprenaient des habitants de zones rurales d'une région d'endémie (n = 200), des migrants de long terme de zones ruraux vers les villes (n = 589) et les personnes vivant dans le même milieu urbain (n = 196). Les troubles épileptiques ont été détectés par un sondage et un neurologue a examiné les répondants positifs. Des échantillons de sérum de 981/985 individus ont été testés pour les anticorps de cysticercose par Immunoblot.
Résultats
La prévalence de l’épilepsie (pour 1000 personnes) était de 15,3 dans le groupe urbain; 35,6 chez les migrants et 25 dans la population rurale. Un gradient dans la séroprévalence des anticorps de la cysticercose a été observé: dans le groupe urbain 2%, le groupe de migrants 13,5% et le groupe rural 18% (p <0,05). Une tendance croissante similaire de séroprévalence plus élevée a été observée chez les migrants selon l’âge à la migration. Chez les villageois ruraux, il y avait des preuves solides d'une association entre une sérologie positive et le fait d'avoir des crises (p = 0,011), mais une telle association n'a pas été observée chez les migrants de long terme ou chez les résidents urbains. Dans l'ensemble de la population de l’étude, ceux avec de fortes réactions d'anticorps (≥ 4 bandes d'anticorps) étaient plus susceptibles d'avoir l’épilepsie (p <0,001) comparé aux participants séronégatifs.
Conclusions
La migration internationale n'est pas la seule qui affecte l'endémicité de la cysticercose; la migration interne peut aussi modifier les profils d'endémicité au sein d'un même pays d'endémie. Les conséquences neurologiques de l'infection par la cysticercose sont susceptibles de survivre à la réponse d'anticorps durant des années après la migration des zones rurales vers les zones urbaines.
Objetivos
Examinar la prevalencia de convulsiones, epilepsia, y seropositividad para cisticercosis entre población rural (de zonas endémicas para cisticercosis), inmigrantes provenientes de zonas rurales a tugurios urbanos no endémicos, y habitantes urbanos de los mismo tugurios urbanos no endémicos.
Métodos
Se estudiaron tres poblaciones peruanas (n=985) originalmente reclutadas en un estudio de enfermedades crónicas y migración. Estos grupos incluían habitantes rurales de una región endémica (n=200), inmigrantes de larga duración de zonas rurales a urbanas (n=589), e individuos que vivían en la misma zona urbana (n=196). Las convulsiones se detectaron mediante una encuesta y un neurólogo examinó a quienes habían respondido positivamente. Se procesaron muestras de suero de 981/985 individuos en busca de anticuerpos para cisticercosis mediante inmunoblot.
Resultados
La prevalencia de epilepsia (por 1,000 personas) era de 15.3 en el grupo urbano, 35.6 en inmigrantes y 25 en habitantes rurales. Se observó un gradiente en la seroprevalencia de los anticuerpos para cisticercosis: grupos urbano 2%, inmigrante 13.5% y rural 18% (p<0.05). Se observó un patrón de aumento similar de mayor seroprevalencia entre inmigrantes según la edad que tenían en el momento de emigrar. En pobladores rurales, había una evidencia importante de asociación entre tener una serología positiva y sufrir convulsiones (p=0.011), pero esta asociación no se observaba en inmigrantes de larga duración o residentes urbanos. En la población al completo, comparada con los participantes seronegativos, aquellos con una fuerte reactividad de anticuerpos (≥4 bandas de anticuerpos) tenían una mayor probabilidad de sufrir epilepsia (p<0.001).
Conclusiones
No solo la migración internacional afecta la endemicidad de cisticercosis; la migración interna también puede afectar los patrones de endemicidad dentro de un país endémico. Las consecuencias neurológicas de la infección por cisticercos podrían durar más que la respuesta a anticuerpos años después de la migración de zonas rurales a zonas urbanas.
doi:10.1111/tmi.12456
PMCID: PMC4355387  PMID: 25581851
cysticercosis; neurocysticercosis; seizures; migration; Taenia solium; Peru
7.  Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 
Newton, John N | Briggs, Adam D M | Murray, Christopher J L | Dicker, Daniel | Foreman, Kyle J | Wang, Haidong | Naghavi, Mohsen | Forouzanfar, Mohammad H | Ohno, Summer Lockett | Barber, Ryan M | Vos, Theo | Stanaway, Jeffrey D | Schmidt, Jürgen C | Hughes, Andrew J | Fay, Derek F J | Ecob, Russell | Gresser, Charis | McKee, Martin | Rutter, Harry | Abubakar, Ibrahim | Ali, Raghib | Anderson, H Ross | Banerjee, Amitava | Bennett, Derrick A | Bernabé, Eduardo | Bhui, Kamaldeep S | Biryukov, Stanley M | Bourne, Rupert R | Brayne, Carol E G | Bruce, Nigel G | Brugha, Traolach S | Burch, Michael | Capewell, Simon | Casey, Daniel | Chowdhury, Rajiv | Coates, Matthew M | Cooper, Cyrus | Critchley, Julia A | Dargan, Paul I | Dherani, Mukesh K | Elliott, Paul | Ezzati, Majid | Fenton, Kevin A | Fraser, Maya S | Fürst, Thomas | Greaves, Felix | Green, Mark A | Gunnell, David J | Hannigan, Bernadette M | Hay, Roderick J | Hay, Simon I | Hemingway, Harry | Larson, Heidi J | Looker, Katharine J | Lunevicius, Raimundas | Lyons, Ronan A | Marcenes, Wagner | Mason-Jones, Amanda J | Matthews, Fiona E | Moller, Henrik | Murdoch, Michele E | Newton, Charles R | Pearce, Neil | Piel, Frédéric B | Pope, Daniel | Rahimi, Kazem | Rodriguez, Alina | Scarborough, Peter | Schumacher, Austin E | Shiue, Ivy | Smeeth, Liam | Tedstone, Alison | Valabhji, Jonathan | Williams, Hywel C | Wolfe, Charles D A | Woolf, Anthony D | Davis, Adrian C J
Lancet (London, England)  2015;386(10010):2257-2274.
Summary
Background
In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond.
Methods
We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters.
Findings
Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0–5·8) from 75·9 years (75·9–76·0) to 81·3 years (80·9–81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3–43·6), whereas DALYs were reduced by 23·8% (20·9–27·1), and YLDs by 1·4% (0·1–2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7–41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1–12·7]) and tobacco (10·7% [9·4–12·0]).
Interpretation
Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation.
Funding
Bill & Melinda Gates Foundation and Public Health England.
doi:10.1016/S0140-6736(15)00195-6
PMCID: PMC4672153  PMID: 26382241
8.  Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study 
BMJ Open  2015;5(12):e008737.
Objectives
To determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time.
Design
Cohort study.
Setting
Primary and secondary care in England.
Population
39 211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥65 and had at least 1 CAP episode between April 1998 and March 2011.
Main outcome measures
The association between hospitalisation within 28 days of CAP diagnosis (a ‘post-CAP’ hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period.
Results
14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998–2000) to 86% (2009–2010). Duration of hospitalisation and 28-day mortality decreased over the study period.
Conclusions
The risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and patient behaviour.
doi:10.1136/bmjopen-2015-008737
PMCID: PMC4679905  PMID: 26631055
EPIDEMIOLOGY; PUBLIC HEALTH
9.  The ‘rule of halves’ does not apply in Peru: Awareness, treatment, and control of hypertension and diabetes in rural, urban and rural-to-urban migrants 
Objective
To determine the awareness, treatment, and control of hypertension and diabetes by migration status.
Design
Cross-sectional study, secondary analyses of the PERU MIGRANT study.
Patients
Rural, rural-to-urban migrants, and urban participants.
Main outcome measures
Awareness, treatment and control of hypertension and diabetes mellitus were calculated using weights to account for participant’s group size.
Results
Of the 205/987 (weighted prevalence 24.1%, 95%CI: 21.1%–27.1%) participants identified as hypertensive 48.3% were aware of their diagnosis, 40% of them were receiving treatment, and 30.4% of those receiving treatment were controlled. Diabetes was present in 33/987 (weighted prevalence 4.6%, 95%CI: 3.1%–6%) and diabetes awareness, treatment and control were 71.1%, 40.6%, and 7.7%, respectively. Sub-optimal control rates, defined as those not meeting blood pressure or glycaemia targets among those with the condition, were 95.1% for hypertension and 97% for diabetes. Higher awareness, treatment and control rates, for both hypertension and diabetes, were observed in rural-to-urban migrants and urban participants compared to rural participants. However, treatment rates were much lower among migrants compared to the urban group.
Conclusions
These results identify major unmet needs in awareness, treatment, and control of hypertension and diabetes. Particular challenges are lack of awareness of both hypertension and diabetes in rural areas, and poor levels of treatment and control among people who have migrated from rural into urban areas.
doi:10.1097/HPC.0b013e318285ef60
PMCID: PMC4656025  PMID: 23680809
Cardiovascular diseases; epidemiology; risk factors; rural health; urban health
10.  Metabolic Abnormalities Are Common among South American Hispanics Subjects with Normal Weight or Excess Body Weight: The CRONICAS Cohort Study 
PLoS ONE  2015;10(11):e0138968.
Objective
We aimed to characterize metabolic status by body mass index (BMI) status.
Methods
The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru’s capital, costal urban, highly urbanized), urban and rural Puno (both high-altitude), and Tumbes (costal semirural). Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30 kg/m2), and as metabolically healthy (0–1 metabolic abnormality) or metabolically unhealthy (≥2 abnormalities). Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance.
Results
A total of 3088 (age 55.6±12.6 years, 51.3% females) had all measurements. Of these, 890 (28.8%), 1361 (44.1%) and 837 (27.1%) were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001). Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile.
Conclusions
Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose.
doi:10.1371/journal.pone.0138968
PMCID: PMC4658165  PMID: 26599322
11.  The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement 
PLoS Medicine  2015;12(10):e1001885.
Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting.
doi:10.1371/journal.pmed.1001885
PMCID: PMC4595218  PMID: 26440803
12.  How Does Cardiovascular Disease First Present in Women and Men? 
Circulation  2015;132(14):1320-1328.
Supplemental Digital Content is available in the text.
Background—
Given the recent declines in heart attack and stroke incidence, it is unclear how women and men differ in first lifetime presentations of cardiovascular diseases (CVDs). We compared the incidence of 12 cardiac, cerebrovascular, and peripheral vascular diseases in women and men at different ages.
Methods and Results—
We studied 1 937 360 people, aged ≥30 years and free from diagnosed CVD at baseline (51% women), using linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry, and mortality (Cardiovascular Research Using LInked Bespoke Studies and Electronic Records [CALIBER] research platform). During 6 years median follow-up between 1997 and 2010, 114 859 people experienced an incident cardiovascular diagnosis, the majority (66%) of which were neither myocardial infarction nor ischemic stroke. Associations of male sex with initial diagnoses of CVD, however, varied from strong (age-adjusted hazard ratios, 3.6–5.0) for abdominal aortic aneurysm, myocardial infarction, and unheralded coronary death (particularly >60 years), through modest (hazard ratio, 1.5–2.0) for stable angina, ischemic stroke, peripheral arterial disease, heart failure, and cardiac arrest, to weak (hazard ratio <1.5) for transient ischemic attack, intracerebral hemorrhage, and unstable angina, and inverse (0.69) for subarachnoid hemorrhage (all P<0.001).
Conclusions—
The majority of initial presentations of CVD are neither myocardial infarction nor ischemic stroke, yet most primary prevention studies focus on these presentations. Sex has differing associations with different CVDs, with implications for risk prediction and management strategies.
Clinical Trial Registration—
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01164371.
doi:10.1161/CIRCULATIONAHA.114.013797
PMCID: PMC4590518  PMID: 26330414
aging; cardiovascular diseases; electronic health records; incidence; population; risk factors; sex
13.  Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis 
BMJ Open  2015;5(9):e007824.
Objectives
Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD.
Design
Systematic review and meta-analysis.
Methods
MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible.
Results
Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case–control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta-analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40).
Conclusions
There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI.
doi:10.1136/bmjopen-2015-007824
PMCID: PMC4567661  PMID: 26362660
14.  Glitazone Treatment and Incidence of Parkinson’s Disease among People with Diabetes: A Retrospective Cohort Study 
PLoS Medicine  2015;12(7):e1001854.
Background
Recent in vitro and animal experiments suggest that peroxisome proliferation-activated receptor gamma (PPARɣ) agonist medications, such as antidiabetic glitazone (GTZ) drugs, are neuroprotective in models of Parkinson’s disease (PD). These findings have not been tested in humans. We hypothesized that individuals prescribed GTZ drugs would have a lower incidence of PD compared to individuals prescribed other treatments for diabetes.
Methods and Findings
Using primary care data from the United Kingdom Clinical Practice Research Datalink (CPRD), we conducted a retrospective cohort study in which individuals with diabetes who were newly prescribed GTZ (GTZ-exposed group) were matched by age, sex, practice, and diabetes treatment stage with up to five individuals prescribed other diabetes treatments (other antidiabetic drug-exposed group). Patients were followed up from 1999 until the first recording of a PD diagnosis, end of observation in the database, or end of the study (1 August 2013). An incidence rate ratio (IRR) was calculated using conditional Poisson regression, adjusted for possible confounders. 44,597 GTZ exposed individuals were matched to 120,373 other antidiabetic users. 175 GTZ-exposed individuals were diagnosed with PD compared to 517 individuals in the other antidiabetic drug-exposed group. The incidence rate (IR) of PD in the GTZ-exposed group was 6.4 per 10,000 patient years compared with 8.8 per 10,000 patient years in those prescribed other antidiabetic treatments (IRR 0.72, 95% confidence interval [CI] 0.60–0.87). Adjustments for potential confounding variables, including smoking, other medications, head injury, and disease severity, had no material impact (fully adjusted IRR 0.75, 0.59–0.94). The risk was reduced in those with current GTZ prescriptions (current GTZ-exposed IRR 0.59, 0.46–0.77) but not reduced among those with past prescriptions (past GTZ-exposed IRR 0.85, 0.65–1.10). Our study only included patients with diabetes who did not have a PD diagnosis when they were first prescribed GTZ, and thus, it cannot establish whether GTZ use prevents or slows the progression of PD.
Conclusions
In patients with diabetes, a current prescription for GTZ is associated with a reduction in incidence of PD. This suggests PPAR gamma pathways may be a fruitful drug target in PD.
In a retrospective cohort study, Ruth Brauer and colleagues examine the association between treatment with glitazone and incidence of Parkinson's disease.
Editors' Summary
Background
Parkinson’s disease (PD) is a common, progressive neurological disease. The condition is caused by the gradual loss of nerve cells that normally produce dopamine, a neurotransmitter that regulates the body’s movements. PD does not usually begin to develop until people are around 60 years old, although it can sometimes affect younger people. Its symptoms, which develop slowly, include tremor (trembling of the hands, legs, arm, jaw, and face), slow movement, and rigidity (muscle stiffness). As these symptoms worsen, affected individuals may have trouble walking, speaking, swallowing, and sleeping, and they may become depressed. No one has found a way to halt the loss of dopamine-producing nerve cells yet, but medications that replace or mimic the lost dopamine can reduce the severity of these symptoms. PD does not directly kill people, but it puts a great strain on the body that can make affected individuals vulnerable to life-threatening infections. Nevertheless, these days, many people with PD have a normal or near-normal life expectancy.
Why Was This Study Done?
Recent experiments suggest that drugs that bind to the peroxisome proliferation-activated receptor gamma (PPARγ agonist medications) may be neuroprotective (prevent nerve cell loss) in animal models of PD. PPARγ regulates how the body uses fats and sugars, and PPARγ agonist medications such as rosiglitazone and pioglitazone (glitazone [GTZ] drugs) are used to treat people with diabetes, a condition characterized by high levels of sugar in the blood. It is not known, however, whether GTZ drugs provide protection against PD in people. In this retrospective cohort study, the researchers investigate whether individuals with diabetes exposed to GTZ drugs have a lower incidence of PD than individuals using other antidiabetic drugs. A retrospective cohort study uses data already collected on a group (cohort) of people to look for associations between specific characteristics such as use of a drug and outcomes.
What Did the Researchers Do and Find?
The researchers identified 44,597 patients with diabetes who were newly exposed to GTZ drugs in the UK Clinical Practice Research Datalink, a database that contains primary care data on more than 13 million individuals. They matched each patient with up to five users of other antidiabetic drugs (120,373 controls) who were similar in terms of age, sex, attendance at the same primary care practice, and diabetes treatment stage; people with diabetes usually initially take a single drug but often switch to a different drug or to a combination of drugs as their disease progresses. Finally, the researchers followed up the entire cohort from January 1999 (when glitazones were introduced to treat diabetes) until diagnosis of PD, the end of inclusion in the database, or the end of the study (August 2013). During follow up, 175 glitazone users and 517 non-glitazone users were diagnosed with PD. The incidence rates of PD among glitazone-using individuals and among users of other antidiabetic treatments were 6.4 per 10,000 patient years and 8.8 per 10,000 patient years, respectively (an incidence rate ratio [IRR] of 0.72; an IRR compares the rate of occurrence of new cases of a disease in two groups of people). Adjustment for potential confounding variables (characteristics that might affect an individual’s likelihood of developing PD) such as smoking and head injury did not alter the IRR. Notably, the risk of PD was reduced among current users of GTZ drugs but not among past users.
What Do These Findings Mean?
These findings indicate that, among people with diabetes, current (but not past) GTZ use is associated with a 28% lower rate of clinical presentation of PD compared to the use of other antidiabetic drugs. Because the study only included patients with diabetes who did not have a PD diagnosis when they started GTZ treatment, these findings cannot establish whether GTZ use is associated with prevention of PD or with slower progression of the disease. Moreover, the accuracy of these findings may be affected by misdiagnosis of PD and misclassification of exposure periods to various antidiabetic drugs in the database and by residual confounding. Finally, these findings may not be applicable to people without diabetes. Importantly, the researchers do not recommend that GTZ drugs (which have been associated with some serious side effects) be used as a treatment for PD. Rather, they suggest that the pathways in which PPARγ is involved might contain potential drug targets for PD and should be investigated in future research.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001854.
The United States National Institute of Neurological Disorders and Stroke provides detailed information about PD (in English and Spanish), including links to US organizations that help people with PD
The UK National Health Service Choices website provides information on all aspects of PD (including personal stories)
The UK not-for-profit organization Parkinson'sUK and the US not-for-profit organization National Parkinson Foundation also provide detailed information about PD and personal stories
The UK not-for-profit organization Healthtalk.Org provides stories about all aspects of living with PD
MedlinePlus has links to further resources about PD and information about rosiglitazone and pioglitazone (in English and Spanish)
doi:10.1371/journal.pmed.1001854
PMCID: PMC4511413  PMID: 26196151
15.  A Systematic Review of Tobacco Smoking Prevalence and Description of Tobacco Control Strategies in Sub-Saharan African Countries; 2007 to 2014 
PLoS ONE  2015;10(7):e0132401.
Objective
To systematically review current smoking prevalence among adults in sub-Saharan Africa from 2007 to May 2014 and to describe the context of tobacco control strategies in these countries.
Data Sources
Five databases, Medline, Embase, Africa-wide Information, Cinahl Plus, and Global Health were searched using a systematic search strategy. There were no language restrictions.
Study Selection
26 included studies measured current smoking prevalence in nationally representative adult populations in sub-Saharan African countries.
Data Extraction
Study details were independently extracted using a standard datasheet. Data on tobacco control policies, taxation and trends in prices were obtained from the Implementation Database of the WHO FCTC website.
Results
Studies represented 13 countries. Current smoking prevalence varied widely ranging from 1.8% in Zambia to 25.8% in Sierra Leone. The prevalence of smoking was consistently lower in women compared to men with the widest gender difference observed in Malawi (men 25.9%, women 2.9%). Rwanda had the highest prevalence of women smokers (12.6%) and Ghana had the lowest (0.2%). Rural, urban patterns were inconsistent. Most countries have implemented demand-reduction measures including bans on advertising, and taxation rates but to different extents.
Conclusion
Smoking prevalence varied widely across sub-Saharan Africa, even between similar country regions, but was always higher in men. High smoking rates were observed among countries in the eastern and southern regions of Africa, mainly among men in Ethiopia, Malawi, Rwanda, and Zambia and women in Rwanda and rural Zambia. Effective action to reduce smoking across sub-Saharan Africa, particularly targeting population groups at increased risk remains a pressing public health priority.
doi:10.1371/journal.pone.0132401
PMCID: PMC4498629  PMID: 26162085
16.  Migration, urbanisation and mortality: 5-year longitudinal analysis of the PERU MIGRANT study 
Objective
To compare all-cause and cause-specific mortality among 3 distinct groups: within-country, rural-to-urban migrants, and rural and urban dwellers in a longitudinal cohort in Peru.
Methods
The PERU MIGRANT Study, a longitudinal cohort study, used an age-stratified and sex-stratified random sample of urban dwellers in a shanty town community in the capital city of Peru, rural dwellers in the Andes, and migrants from the Andes to the shanty town community. Participants underwent a questionnaire and anthropomorphic measurements at a baseline evaluation in 2007–2008 and at a follow-up visit in 2012–2013. Mortality was determined by death certificate or family interview.
Results
Of the 989 participants evaluated at baseline, 928 (94%) were evaluated at follow-up (mean age 48 years; 53% female). The mean follow-up time was 5.1 years, totalling 4732.8 person-years. In a multivariable survival model, and relative to urban dwellers, rural participants had lower all-cause mortality (HR=0.27; 95% CI 0.07 to 0.98), and both the rural (HR=0.07; 95% CI 0.01 to 0.87) and migrant (HR=0.13; 95% CI 0.02 to 0.81) groups had lower cardiovascular mortality.
Conclusions
Cardiovascular mortality of migrants remains similar to that of the rural group, suggesting that rural-to-urban migrants do not appear to catch up with urban mortality in spite of having a more urban cardiovascular risk factor profile.
doi:10.1136/jech-2015-205657
PMCID: PMC4494660  PMID: 25987723
17.  Congenital Anomalies in Children of Mothers Taking Antiepileptic Drugs with and without Periconceptional High Dose Folic Acid Use: A Population-Based Cohort Study 
PLoS ONE  2015;10(7):e0131130.
Background
Antenatal antiepileptic drug (AED) use has been found to be associated with increased major congenital anomaly (CA) risks. However whether such AED-associated risks were different according to periconceptional high dose (5mg daily) folic acid supplementation is still unclear.
Methods
We included 258,591 singleton live-born children of mothers aged 15-44 years in 1990-2013 from The Health Improvement Network, a large UK primary care database. We identified all major CAs according to the European Surveillance of Congenital Anomalies classification. Absolute risks and adjusted odds ratios (aOR) were calculated comparing children of mothers prescribed AEDs to those without such prescriptions, stratified by folic acid prescriptions around the time of conception (one month before conception to two months post-conception).
Results
CA risk was 476/10,000 in children of mothers with first trimester AEDs compared with 269/10,000 in those without AEDs equating to an aOR of 1.82, 95% confidence interval 1.30-2.56. The highest system-specific risks were for heart anomalies (198/10,000 and 79/10,000 respectively, aOR 2.49,1.47-4.21). Sodium valproate and lamotrigine were both associated with increased risks of any CA (aOR 2.63,1.46-4.74 and aOR 2.01,1.12-3.59 respectively) and system-specific risks. Stratification by folic acid supplementation did not show marked reductions in AED-associated risks (e.g. for CAs overall aOR 1.75, 1.01-3.03 in the high dose folic acid group and 1.94, 95%CI 1.21-3.13 in the low dose or no folic acid group); however, the majority of mothers taking AEDs only initiated high dose folic acid from the second month of pregnancy.
Conclusions
Children of mothers with AEDs in the first trimester of pregnancy have a 2-fold increased risk of major CA compared to those unexposed. We found no evidence that prescribed high dose folic acid supplementation reduced such AED-associated risks. Although statistical power was limited, prescribing of folic acid too late for it to be effective during the organogenic period or selective prescribing to those with more severe morbidity may explain these findings.
doi:10.1371/journal.pone.0131130
PMCID: PMC4492893  PMID: 26147467
18.  Data Resource Profile: Clinical Practice Research Datalink (CPRD) 
The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.
doi:10.1093/ije/dyv098
PMCID: PMC4521131  PMID: 26050254
19.  Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink 
BMC Medicine  2015;13:135.
Background
Previous cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB.
We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening.
Methods
Using data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990–2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates.
Results
During just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons).
Conclusions
Diabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0381-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-015-0381-9
PMCID: PMC4470065  PMID: 26048371
Tuberculosis; Diabetes; CPRD; Epidemiology; Cohort
20.  High prevalence of hypertension and of risk factors for non-communicable diseases (NCDs): a population based cross-sectional survey of NCDS and HIV infection in Northwestern Tanzania and Southern Uganda 
BMC Medicine  2015;13:126.
Background
The burden of non-communicable diseases (NCDs) is increasing in sub-Saharan Africa, but data available for intervention planning are inadequate. We determined the prevalence of selected NCDs and HIV infection, and NCD risk factors in northwestern Tanzania and southern Uganda.
Methods
A population-based cross-sectional survey was conducted, enrolling households using multistage sampling with five strata per country (one municipality, two towns, two rural areas). Consenting adults (≥18 years) were interviewed using the WHO STEPS survey instrument, examined, and tested for HIV and diabetes mellitus (DM). Adjusting for survey design, we estimated population prevalences of hypertension, DM, obstructive pulmonary disease, cardiac failure, epilepsy and HIV, and investigated factors associated with hypertension using logistic regression.
Results
Across strata, hypertension prevalence ranged from 16 % (95 % confidence interval (CI): 12 % to 22 %) to 17 % (CI: 14 % to 22 %) in Tanzania, and from 19 % (CI: 14 % to 26 %) to 26 % (CI: 23 % to 30 %) in Uganda. It was high in both urban and rural areas, affecting many young participants. The prevalence of DM (1 % to 4 %) and other NCDs was generally low. HIV prevalence ranged from 6 % to 10 % in Tanzania, and 6 % to 12 % in Uganda. Current smoking was reported by 12 % to 23 % of men in different strata, and 1 % to 3 % of women. Problem drinking (defined by Alcohol Use Disorder Identification Test criteria) affected 6 % to 15 % men and 1 % to 6 % women. Up to 46 % of participants were overweight, affecting women more than men and urban more than rural areas. Most patients with hypertension and other NCDs were unaware of their condition, and hypertension in treated patients was mostly uncontrolled. Hypertension was associated with older age, male sex, being divorced/widowed, lower education, higher BMI and, inversely, with smoking.
Conclusions
The high prevalence of NCD risk factors and unrecognized and untreated hypertension represent major problems. The low prevalence of DM and other preventable NCDs provides an opportunity for prevention. HIV prevalence was in line with national data. In Tanzania, Uganda and probably elsewhere in Africa, major efforts are needed to strengthen health services for the PREVENTION, early detection and treatment of chronic diseases.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-015-0357-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-015-0357-9
PMCID: PMC4476208  PMID: 26021319
Non-communicable diseases; hypertension; diabetes mellitus; heart failure; obstructive pulmonary disease; HIV infection; NCD risk factors; WHO STEPS survey; Africa
21.  The REporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) Statement: Methods for Arriving at Consensus and Developing Reporting Guidelines 
PLoS ONE  2015;10(5):e0125620.
Objective
Routinely collected health data, collected for administrative and clinical purposes, without specific a priori research questions, are increasingly used for observational, comparative effectiveness, health services research, and clinical trials. The rapid evolution and availability of routinely collected data for research has brought to light specific issues not addressed by existing reporting guidelines. The aim of the present project was to determine the priorities of stakeholders in order to guide the development of the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.
Methods
Two modified electronic Delphi surveys were sent to stakeholders. The first determined themes deemed important to include in the RECORD statement, and was analyzed using qualitative methods. The second determined quantitative prioritization of the themes based on categorization of manuscript headings. The surveys were followed by a meeting of RECORD working committee, and re-engagement with stakeholders via an online commentary period.
Results
The qualitative survey (76 responses of 123 surveys sent) generated 10 overarching themes and 13 themes derived from existing STROBE categories. Highest-rated overall items for inclusion were: Disease/exposure identification algorithms; Characteristics of the population included in databases; and Characteristics of the data. In the quantitative survey (71 responses of 135 sent), the importance assigned to each of the compiled themes varied depending on the manuscript section to which they were assigned. Following the working committee meeting, online ranking by stakeholders provided feedback and resulted in revision of the final checklist.
Conclusions
The RECORD statement incorporated the suggestions provided by a large, diverse group of stakeholders to create a reporting checklist specific to observational research using routinely collected health data. Our findings point to unique aspects of studies conducted with routinely collected health data and the perceived need for better reporting of methodological issues.
doi:10.1371/journal.pone.0125620
PMCID: PMC4428635  PMID: 25965407
22.  Angiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink 
Aims
This was a cohort study to evaluate whether 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.
Results
A 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 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 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% confidence interval 0.50–0.72).
Conclusions
A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users.
doi:10.1111/bcp.12511
PMCID: PMC4309639  PMID: 25223602
angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; dementia
23.  Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people 
Summary
Background
The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.
Methods
We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439).
Findings
Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1–10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76–3·22]), ischaemic stroke (1·72 [1·52–1·95]), stable angina (1·62 [1·49–1·77]), heart failure (1·56 [1·45–1·69]), and non-fatal myocardial infarction (1·54 [1·42–1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35–0·59]) and subarachnoid haemorrhage (0·48 [0·26–0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76–1·19]).
Interpretation
Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design.
Funding
Wellcome Trust, National Institute for Health Research, and Medical Research Council.
doi:10.1016/S2213-8587(14)70219-0
PMCID: PMC4303913  PMID: 25466521
24.  Heterogeneous associations between smoking and a wide range of initial presentations of cardiovascular disease in 1 937 360 people in England: lifetime risks and implications for risk prediction 
Background It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation.
Methods Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997–2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme).
Results During 11.6 million person-years of follow-up, 114 859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers’ lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR) = 1.04, 95% confidence interval (CI) 0.91–1.19).The strength of association differed markedly according to disease type: stable angina (HR = 1.08, 95% CI 1.01–1.15),transient ischaemic attack (HR = 1.41, 95% CI 1.28-1.55), unstable angina (HR = 1.54, 95% CI 1.38–1.72), intracerebral haemorrhage (HR = 1.61, 95% CI 1.37–1.89), heart failure (HR = 1.62, 95% CI 1.47–1.79), ischaemic stroke (HR = 1.90, 95% CI 1.72–2.10), MI (HR = 2.32, 95% CI 2.20–2.45), SAH (HR = 2.70, 95% CI 2.27–3.21), PAD (HR = 5.16, 95% CI 4.80–5.54) and abdominal aortic aneurysm (AAA) (HR = 5.18, 95% CI 4.61–5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR = 1.36, 1.47 and 2.74, respectively).
Conclusions The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction.
doi:10.1093/ije/dyu218
PMCID: PMC4339760  PMID: 25416721
Association study; cardiovascular outcomes; epidemiology; initial presentation; lifetime risks; primary prevention; smoking; risk prediction; risk stratification
25.  Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials 
Aims
To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy.
Methods
We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group's specialized register, MEDLINE (1950 to March 2009), EMBASE (1980 to March 2009), and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis.
Results
Forty-three eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only three direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio (OR] 3.78, 95% CI 3.14, 4.55) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritized oxcarbazepine, topiramate and pregabalin on the basis of short term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritized on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognized as being associated with serious visual disturbance with chronic use.
Conclusion
Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters.
doi:10.1111/bcp.12083
PMCID: PMC3853525  PMID: 23351090
anticonvulsants/therapeutic use; comparative study; epilepsy/drug therapy; meta-analysis; review; treatment outcome

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