Showing papers in "BMC Medicine in 2014"
TL;DR: Mortality from liver cirrhosis was also comparatively high in Central Asia countries, particularly Mongolia, Uzbekistan and Kyrgyzstan, and in parts of sub-Saharan Africa, notably Gabon.
Abstract: Liver cirrhosis is a major yet largely preventable and underappreciated cause of global health loss. Variations in cirrhosis mortality at the country level reflect differences in prevalence of risk factors such as alcohol use and hepatitis B and C infection. We estimated annual age-specific mortality from liver cirrhosis in 187 countries between 1980 and 2010. We systematically collected vital registration and verbal autopsy data on liver cirrhosis mortality for the period 1980 to 2010. We corrected for misclassification of deaths, which included deaths attributed to improbable or nonfatal causes. We used ensemble models to estimate liver cirrhosis mortality with uncertainty by age, sex, country and year. We used out-of-sample predictive validity to select the optimal model. Global liver cirrhosis deaths increased from around 676,000 (95% uncertainty interval: 452,863 to 1,004,530) in 1980 to over 1 million (1,029,042; 670,216 to 1,554,530) in 2010 (about 2% of the global total). Over the same period, the age-standardized cirrhosis mortality rate decreased by 22%. This was largely driven by decreasing cirrhosis mortality rates in China, the US and countries in Western Europe. In 2010, Egypt, followed by Moldova, had the highest age-standardized cirrhosis mortality rates, 72.7 and 71.2 deaths per 100,000, respectively, while Iceland had the lowest. In Egypt, almost one-fifth (18.1%) of all deaths in males 45- to 54-years old were due to liver cirrhosis. Liver cirrhosis mortality in Mexico is the highest in Latin America. In France and Italy, liver cirrhosis mortality fell by 50% to 60%; conversely, in the United Kingdom, mortality increased by about one-third. Mortality from liver cirrhosis was also comparatively high in Central Asia countries, particularly Mongolia, Uzbekistan and Kyrgyzstan, and in parts of sub-Saharan Africa, notably Gabon. Liver cirrhosis is a significant cause of global health burden, with more than one million deaths in 2010. Our study identifies areas with high and/or rapidly increasing mortality where preventive measures to control and reduce liver cirrhosis risk factors should be urgently strengthened. Please see related commentary: http://www.biomedcentral.com/1741-7015/12/159/abstract
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815 citations
TL;DR: The most frequent vascular pathologies in the aging brain and in AD are cerebral amyloid angiopathy and small vessel disease as mentioned in this paper, which suggest additive or synergistic effects of both pathologies on cognitive decline.
Abstract: Recent epidemiological and clinico-pathological data indicate considerable overlap between cerebrovascular disease (CVD) and Alzheimer’s disease (AD) and suggest additive or synergistic effects of both pathologies on cognitive decline. The most frequent vascular pathologies in the aging brain and in AD are cerebral amyloid angiopathy and small vessel disease. Up to 84% of aged subjects show morphological substrates of CVD in addition to AD pathology. AD brains with minor CVD, similar to pure vascular dementia, show subcortical vascular lesions in about two-thirds, while in mixed type dementia (AD plus vascular dementia), multiple larger infarcts are more frequent. Small infarcts in patients with full-blown AD have no impact on cognitive decline but are overwhelmed by the severity of Alzheimer pathology, while in early stages of AD, cerebrovascular lesions may influence and promote cognitive impairment, lowering the threshold for clinically overt dementia. Further studies are warranted to elucidate the many hitherto unanswered questions regarding the overlap between CVD and AD as well as the impact of both CVD and AD pathologies on the development and progression of dementia.
504 citations
TL;DR: Clinicians and researchers with an interest in the effect of diet on health are asked to describe what constitutes a Mediterranean diet in different geographical settings, and how they can study the health benefits of this dietary pattern.
Abstract: The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern.
435 citations
TL;DR: It is shown that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread.
Abstract: The complex and unprecedented Ebola epidemic ongoing in West Africa has highlighted the need to review the epidemiological characteristics of Ebola Virus Disease (EVD) as well as our current understanding of the transmission dynamics and the effect of control interventions against Ebola transmission Here we review key epidemiological data from past Ebola outbreaks and carry out a comparative review of mathematical models of the spread and control of Ebola in the context of past outbreaks and the ongoing epidemic in West Africa We show that mathematical modeling offers useful insights into the risk of a major epidemic of EVD and the assessment of the impact of basic public health measures on disease spread We also discuss the critical need to collect detailed epidemiological data in real-time during the course of an ongoing epidemic, carry out further studies to estimate the effectiveness of interventions during past outbreaks and the ongoing epidemic, and develop large-scale modeling studies to study the spread and control of viral hemorrhagic fevers in the context of the highly heterogeneous economic reality of African countries
384 citations
TL;DR: Findings suggest that adherence-enhancing interventions should particularly target psychological factors such as self-efficacy and concerns/beliefs about the efficacy and safety of ART, and that simplification of regimens might have smaller but significant effects.
Abstract: Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adherence. We searched PubMed for original English-language papers, published between 1996 and June 2014, and the reference lists of all relevant articles found. Studies reporting on predictors/correlates of adherence of adults prescribed ART for chronic HIV infection were included without restriction to adherence assessment method, study design or geographical location. Two researchers independently extracted the data from the same papers. Random effects models with inverse variance weights were used to aggregate findings into pooled effects estimates with 95% confidence intervals. The standardized mean difference (SMD) was used as the common effect size. The impact of study design features (adherence assessment method, study design, and the United Nations Human Development Index (HDI) of the country in which the study was set) was investigated using categorical mixed effects meta-regression. In total, 207 studies were included. The following predictors/correlates were most strongly associated with adherence: adherence self-efficacy (SMD = 0.603, P = 0.001), current substance use (SMD = -0.395, P = 0.001), concerns about ART (SMD = -0.388, P = 0.001), beliefs about the necessity/utility of ART (SMD = 0.357, P = 0.001), trust/satisfaction with the HIV care provider (SMD = 0.377, P = 0.001), depressive symptoms (SMD = -0.305, P = 0.001), stigma about HIV (SMD = -0.282, P = 0.001), and social support (SMD = 0.237, P = 0.001). Smaller but significant associations were observed for the following being prescribed a protease inhibitor-containing regimen (SMD = -0.196, P = 0.001), daily dosing frequency (SMD = -0.193, P = 0.001), financial constraints (SMD -0.187, P = 0.001) and pill burden (SMD = -0.124, P = 0.001). Higher trust/satisfaction with the HIV care provider, a lower daily dosing frequency, and fewer depressive symptoms were more strongly related with higher adherence in low and medium HDI countries than in high HDI countries. These findings suggest that adherence-enhancing interventions should particularly target psychological factors such as self-efficacy and concerns/beliefs about the efficacy and safety of ART. Moreover, these findings suggest that simplification of regimens might have smaller but significant effects.
370 citations
TL;DR: The SASA! study assessed the community-level impact of SASA!, a community mobilization intervention to prevent violence and reduce HIV-risk behaviors in Kampala, Uganda, and found that women experiencing violence in intervention communities were more likely to receive supportive community responses.
Abstract: Background: Intimate partner violence (IPV) and HIV are important and interconnected public health concerns. While it is recognized that they share common social drivers, there is limited evidence surrounding the potential of community interventions to reduce violence and HIV risk at the community level. The SASA! study assessed the community-level impact of SASA!, a community mobilization intervention to prevent violence and reduce HIV-risk behaviors. Methods: From 2007 to 2012 a pair-matched cluster randomized controlled trial (CRT) was conducted in eight communities (four intervention and four control) in Kampala, Uganda. Cross-sectional surveys of a random sample of community members, 18- to 49-years old, were undertaken at baseline (n = 1,583) and four years post intervention implementation (n = 2,532). Six violence and HIV-related primary outcomes were defined ap riori .A n adjusted cluster-level intention-to-treat analysis compared outcomes in intervention and control communities at follow-up. Results: The intervention was associated with significantly lower social acceptance of IPV among women (adjusted risk ratio 0.54, 95% confidence interval (CI) 0.38 to 0.79) and lower acceptance among men (0.13, 95% CI 0.01 to 1.15); significantly greater acceptance that a woman can refuse sex among women (1.28, 95% CI 1.07 to 1.52) and men (1.31, 95% CI 1.00 to 1.70); 52% lower past year experience of physical IPV among women (0.48, 95% CI 0.16 to 1.39); and lower levels of past year experience of sexual IPV (0.76, 95% CI 0.33 to 1.72). Women experiencing violence in intervention communities were more likely to receive supportive community responses. Reported past year sexual concurrency by men was signi ficantly lower in intervention compared to control communities (0.57, 95% CI 0.36 to 0.91). Conclusions: This is the first CRT in sub-Saharan Africa to assess the community impact of a mobilization program on the social acceptability of IPV, the past year prevalence of IPV and levels of sexual concurrency. SASA! achieved important community impacts, and is now being delivered in control communities and replicated in 15 countries. Trial registration: ClinicalTrials.gov #NCT00790959, Study protocol available at http://www.trialsjournal.com/content/13/1/96
359 citations
TL;DR: The conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental, and understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.
Abstract: Delirium is a common and serious problem among acutely unwell persons. Alhough linked to higher rates of mortality, institutionalisation and dementia, it remains underdiagnosed. Careful consideration of its phenomenology is warranted to improve detection and therefore mitigate some of its clinical impact. The publication of the fifth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) provides an opportunity to examine the constructs underlying delirium as a clinical entity. Altered consciousness has been regarded as a core feature of delirium; the fact that consciousness itself should be physiologically disrupted due to acute illness attests to its clinical urgency. DSM-5 now operationalises `consciousness’ as `changes in attention’. It should be recognised that attention relates to content of consciousness, but arousal corresponds to level of consciousness. Reduced arousal is also associated with adverse outcomes. Attention and arousal are hierarchically related; level of arousal must be sufficient before attention can be reasonably tested. Our conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental. Understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.
321 citations
TL;DR: Current guidance documents on the assessment and treatment of hyponatremia vary in methodological rigor and recommendations are not always consistent.
Abstract: Background
Hyponatremia is a common electrolyte disorder. Multiple organizations have published guidance documents to assist clinicians in managing hyponatremia. We aimed to explore the scope, content, and consistency of these documents.
301 citations
TL;DR: There is a need for more research looking at the ways in which having dementia impacts on clinical care for other conditions and how the process of care and different services are adapting to the needs of people with dementia and comorbidity.
Abstract: Background: Evidence suggests that amongst people with dementia there is a high prevalence of comorbid medical conditions and related complaints. The presence of dementia may complicate clinical care for other conditions and undermine a patient’s ability to manage a chronic condition. The aim of this study was to scope the extent, range and nature of research activity around dementia and comorbidity. Methods: We undertook a scoping review including all types of research relating to the prevalence of comorbidities in people with dementia; current systems, structures and other issues relating to service organisation and delivery; patient and carer experiences; and the experiences and attitudes of service providers. We searched AMED, Cochrane Library, CINAHL, PubMed, NHS Evidence, Scopus, Google Scholar (searched 2012, Pubmed updated 2013), checked reference lists and performed citation searches on PubMed and Google Scholar (ongoing to February 2014). Results: We included 54 primary studies, eight reviews and three guidelines. Much of the available literature relates to the prevalence of comorbidities in people with dementia or issues around quality of care. Less is known about service organisation and delivery or the views and experiences of people with dementia and their family carers. There is some evidence that people with dementia did not have the same access to treatment and monitoring for conditions such as visual impairment and diabetes as those with similar comorbidities but without dementia. Conclusions: The prevalence of comorbid conditions in people with dementia is high. Whilst current evidence suggests that people with dementia may have poorer access to services the reasons for this are not clear. There is a need for more research looking at the ways in which having dementia impacts on clinical care for other conditions and how the process of care and different services are adapting to the needs of people with dementia and comorbidity. People with dementia should be included in the debate about the management of comorbidities in older populations and there needs to be greater consideration given to including them in studies that focus on age-related healthcare issues.
298 citations
TL;DR: Higher intake of yogurt is associated with a reduced risk of type 2 diabetes, whereas other dairy foods and consumption of total dairy are not appreciably associated with incidence of T2D.
Abstract: The relation between consumption of different types of dairy and risk of type 2 diabetes (T2D) remains uncertain. Therefore, we aimed to evaluate the association between total dairy and individual types of dairy consumptions and incident T2D in US adults. We followed 41,436 men in the Health Professionals Follow-Up Study (1986 to 2010), 67,138 women in the Nurses’ Health Study (1980 to 2010), and 85,884 women in the Nurses’ Health Study II (1991 to 2009). Diet was assessed by validated food-frequency questionnaires, and data were updated every four years. Incident T2D was confirmed by a validated supplementary questionnaire. During 3,984,203 person-years of follow-up, we documented 15,156 incident T2D cases. After adjustment for age, body mass index (BMI) and other lifestyle and dietary risk factors, total dairy consumption was not associated with T2D risk and the pooled hazard ratio (HR) (95% confidence interval (CI)) of T2D for one serving/day increase in total dairy was 0.99 (0.98, 1.01). Among different types of dairy products, neither low-fat nor high-fat dairy intake was appreciably associated with risk of T2D. However, yogurt intake was consistently and inversely associated with T2D risk across the three cohorts with the pooled HR of 0.83 (0.75, 0.92) for one serving/day increment (P for trend <0.001). We conducted a meta-analysis of 14 prospective cohorts with 459,790 participants and 35,863 incident T2D cases; the pooled relative risks (RRs) (95% CIs) were 0.98 (0.96, 1.01) and 0.82 (0.70, 0.96) for one serving total dairy/day and one serving yogurt/day, respectively. Higher intake of yogurt is associated with a reduced risk of T2D, whereas other dairy foods and consumption of total dairy are not appreciably associated with incidence of T2D.
287 citations
Rovira i Virgili University1, Carlos III Health Institute2, Harvard University3, University of Navarra4, Barcelona Biomedical Research Park5, University of Barcelona6, University of Valencia7, University of Málaga8, University of Las Palmas de Gran Canaria9, Bellvitge University Hospital10, Spanish National Research Council11
TL;DR: Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk.
Abstract: Background: It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk. Methods: We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvencion con DIeta MEDiterranea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality. Results: During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group. Conclusions: Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk.
TL;DR: This prospective survey shows that non-celiac gluten sensitivity has a strong correlation with female gender and adult age, and the prevalence of NCGS seems to be only slightly higher than that of celiac disease.
Abstract: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86
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TL;DR: Stable and protective childhoods are critical factors in the development of resilience to health-harming behaviors in England, with nurturing childhoods supporting the adoption of health-benefiting behaviors and the provision of positive childhood environments for future generations.
Abstract: Background: Epidemiological and biomedical evidence link adverse childhood experiences (ACEs) with health-harming behaviors and the development of non-communicable disease in adults. Investment in interventions to improve early life experiences requires empirical evidence on levels of childhood adversity and the proportion of HHBs potentially avoided should such adversity be addressed. Methods: A nationally representative survey of English residents aged 18 to 69 (n = 3,885) was undertaken during the period April to July 2013. Individuals were categorized according to the number of ACEs experienced. Modeling identified the proportions of HHBs (early sexual initiation, unintended teenage pregnancy, smoking, binge drinking, drug use, violence victimization, violence perpetration, incarceration, poor diet, low levels of physical exercise) independently associated with ACEs at national population levels. Results: Almost half (47%) of individuals experienced at least one of the nine ACEs. Prevalence of childhood sexual, physical, and verbal abuse was 6.3%, 14.8%, and 18.2% respectively (population-adjusted). After correcting for sociodemographics, ACE counts predicted all HHBs, e.g. (0 versus 4+ ACEs, adjusted odds ratios (95% confidence intervals)): smoking 3.29 (2.54 to 4.27); violence perpetration 7.71 (4.90 to 12.14); unintended teenage pregnancy 5.86 (3.93 to 8.74). Modeling suggested that 11.9% of binge drinking, 13.6% of poor diet, 22.7% of smoking, 52.0% of violence perpetration, 58.7% of heroin/crack cocaine use, and 37.6% of unintended teenage pregnancy prevalence nationally could be attributed to ACEs. Conclusions: Stable and protective childhoods are critical factors in the development of resilience to health-harming behaviors in England. Interventions to reduce ACEs are available and sustainable, with nurturing childhoods supporting the adoption of health-benefiting behaviors and ultimately the provision of positive childhood environments for future generations.
TL;DR: New Global Burden of Disease estimates for liver Cirrhosis, published in BMC Medicine, suggest that cirrhosis caused over a million deaths in 2010, with a further million due to liver cancer and acute hepatitis.
Abstract: New Global Burden of Disease estimates for liver cirrhosis, published in BMC Medicine, suggest that cirrhosis caused over a million deaths in 2010, with a further million due to liver cancer and acute hepatitis. Cause-specific mortality data were very sparse for some regions, particularly in Africa, with no relevant mortality data for 58/187 countries. Liver disease involves infectious, malignant and chronic aetiologies with overlapping symptoms. Where available mortality data come from verbal autopsies, separating different types of liver disease is challenging. Cirrhosis is a disease of rich and poor alike; key public health risk factors such as alcohol consumption play an important role. Risk-reduction strategies such as controlling the price of alcohol are being widely discussed. Since these estimates used alcohol consumption as a covariate, they cannot be used to explore relationships between alcohol consumption and cirrhosis mortality. There is hope: coming generations of adults will have been vaccinated against hepatitis B, and this is envisaged to reduce the burden of fatal liver disease. But more complete civil registration globally is needed to fully understand the burden of liver disease. Please see related article: http://www.biomedcentral.com/1741-7015/12/145/abstract.
TL;DR: Epidemiological evidence for a beneficial effect of low alcohol consumption without heavy drinking episodes is strong, corroborated by experimental evidence, however, episodic and chronic heavy drinking do not provide any beneficial effect on IHD.
Abstract: Alcohol consumption is a major global risk factor for mortality and morbidity. Much discussion has revolved around the diverse findings on the complex relationship between alcohol consumption and the leading cause of death and disability, ischemic heart disease (IHD). We conducted a systematic search of the literature up to August 2014 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify meta-analyses and observational studies examining the relationship between alcohol drinking, drinking patterns, and IHD risk, in comparison to lifetime abstainers. In a narrative review we have summarized the many meta-analyses published in the last 10 years, discussing the role of confounding and experimental evidence. We also conducted meta-analyses examining episodic heavy drinking among on average moderate drinkers. The narrative review showed that the use of current abstainers as the reference group leads to systematic bias. With regard to average alcohol consumption in relation to lifetime abstainers, the relationship is clearly J-shaped, supported by short-term experimental evidence and similar associations within strata of potential confounders, except among smokers. Women experience slightly stronger beneficial associations and also a quicker upturn to a detrimental effect at lower levels of average alcohol consumption compared to men. There was no evidence that chronic or episodic heavy drinking confers a beneficial effect on IHD risk. People with alcohol use disorder have an elevated risk of IHD (1.5- to 2-fold). Results from our quantitative meta-analysis showed that drinkers with average intake of <30 g/day and no episodic heavy drinking had the lowest IHD risk (relative risk = 0.64, 95% confidence interval 0.53 to 0.71). Drinkers with episodic heavy drinking occasions had a risk similar to lifetime abstainers (relative risk = 1.12, 95% confidence interval 0.91 to 1.37). Epidemiological evidence for a beneficial effect of low alcohol consumption without heavy drinking episodes is strong, corroborated by experimental evidence. However, episodic and chronic heavy drinking do not provide any beneficial effect on IHD. Thus, average alcohol consumption is not sufficient to describe the risk relation between alcohol consumption and IHD. Alcohol policy should try to reduce heavy drinking patterns.
TL;DR: The interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity, and the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression.
Abstract: Major depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction. A literature search was conducted using PsychINFO and PubMed databases until 22 November 2013. A total of 22 studies with a pooled total of 14,233 participants met the inclusion criteria, the results of which were combined and a meta-analysis performed using the Liptak-Stouffer z-score method. The results suggest that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (P = 0.03). When the studies were stratified by type of environmental stressor, the evidence was stronger for an interaction with stressful life events (P = 0.01) and weaker for interaction of BDNF Val66Met with childhood adversity (P = 0.051). The interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity. Methodological limitations of existing studies include poor measurement of life stress.
TL;DR: Findings on cardiovascular disease (CVD) and risk factors in the etiology of AD are summarized and the relation between imaging makers of pre-clinical vascular disease and AD is summarized.
Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD.
TL;DR: To provide orientation in decision making in multimorbidity during primary care consultations, guiding principles are developed and named after the Greek mythological figure Ariadne and recognized and appreciated as important by family physicians and primary care researchers.
Abstract: Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patientcentered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient’s preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers. Please see related article: http://www.biomedcentral.com/1741-7015/12/222.
TL;DR: Low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity made it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms.
Abstract: The ‘Older People’s Exercise intervention in Residential and nursing Accommodation’ (OPERA) cluster randomised trial evaluated the impact of training for care home staff together with twice-weekly, physiotherapist-led exercise classes on depressive symptoms in care home residents, but found no effect. We report a process evaluation exploring potential explanations for the lack of effect. The OPERA trial included over 1,000 residents in 78 care homes in the UK. We used a mixed methods approach including quantitative data collected from all homes. In eight case study homes, we carried out repeated periods of observation and interviews with residents, care staff and managers. At the end of the intervention, we held focus groups with OPERA research staff. We reported our first findings before the trial outcome was known. Homes showed large variations in activity at baseline and throughout the trial. Overall attendance rate at the group exercise sessions was low (50%). We considered two issues that might explain the negative outcome: whether the intervention changed the culture of the homes, and whether the residents engaged with the intervention. We found low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity. The trial team delivered 3,191 exercise groups but only 36% of participants attended at least 1 group per week and depressed residents attended significantly fewer groups than those who were not depressed. Residents were very frail and therefore most groups only included seated exercises. The intervention did not change the culture of the homes and, in the case study homes, activity levels did not change outside the exercise groups. Residents did not engage in the exercise groups at a sufficient level, and this was particularly true for those with depressive symptoms at baseline. The physical and mental frailty of care home residents may make it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms.
TL;DR: The opsonic phagocytosis assay appears to be a strong correlate of protection against malaria, a valuable biomarker of immunity, and provides a much-needed new tool for assessing responses to blood-stage malaria vaccines and measuring immunity in populations.
Abstract: An understanding of the mechanisms mediating protective immunity against malaria in humans is currently lacking, but critically important to advance the development of highly efficacious vaccines. Antibodies play a key role in acquired immunity, but the functional basis for their protective effect remains unclear. Furthermore, there is a strong need for immune correlates of protection against malaria to guide vaccine development. Using a validated assay to measure opsonic phagocytosis of Plasmodium falciparum merozoites, we investigated the potential role of this functional activity in human immunity against clinical episodes of malaria in two independent cohorts (n = 109 and n = 287) experiencing differing levels of malaria transmission and evaluated its potential as a correlate of protection. Antibodies promoting opsonic phagocytosis of merozoites were cytophilic immunoglobulins (IgG1 and IgG3), induced monocyte activation and production of pro-inflammatory cytokines, and were directed against major merozoite surface proteins (MSPs). Consistent with protective immunity in humans, opsonizing antibodies were acquired with increasing age and malaria exposure, were boosted on re-infection, and levels were related to malaria transmission intensity. Opsonic phagocytosis was strongly associated with a reduced risk of clinical malaria in longitudinal studies in children with current or recent infections. In contrast, antibodies to the merozoite surface in standard immunoassays, or growth-inhibitory antibodies, were not significantly associated with protection. In multivariate analyses including several antibody responses, opsonic phagocytosis remained significantly associated with protection against malaria, highlighting its potential as a correlate of immunity. Furthermore, we demonstrate that human antibodies against MSP2 and MSP3 that are strongly associated with protection in this population are effective in opsonic phagocytosis of merozoites, providing a functional link between these antigen-specific responses and protection for the first time. Opsonic phagocytosis of merozoites appears to be an important mechanism contributing to protective immunity in humans. The opsonic phagocytosis assay appears to be a strong correlate of protection against malaria, a valuable biomarker of immunity, and provides a much-needed new tool for assessing responses to blood-stage malaria vaccines and measuring immunity in populations.
TL;DR: A cumulative effect of public health programs for obesity prevention resulting in an increase in physical activity, and a decline in television viewing and in the consumption of sugar-sweetened soft drinks by children is postulated.
Abstract: Surveys performed in the past 10 to 15 years show a yet unexplained stabilization or decline in prevalence rates of childhood obesity in developed countries. The projected continuous increase in obesity prevalence throughout future decades seems not to occur at present. Apparently, saturation has been reached, which might be related to societal adjustments. Hence, we postulate a cumulative effect of public health programs for obesity prevention resulting, for example, in an increase in physical activity, and a decline in television viewing and in the consumption of sugar-sweetened soft drinks by children. Effective public health programs are urgently needed for developing countries, where obesity rates in children still continued to increase during the past decade.
TL;DR: Antibiotic use has decreased among children and adolescents, but has increased for older adults, and broad-spectrum antibiotic prescribing continues to be on the rise.
Abstract: The use of antibiotics is the single most important driver in antibiotic resistance. Nevertheless, antibiotic overuse remains common. Decline in antibiotic prescribing in the United States coincided with the launch of national educational campaigns in the 1990s and other interventions, including the introduction of routine infant immunizations with the pneumococcal conjugate vaccine (PCV-7); however, it is unknown if these trends have been sustained through recent measurements. We performed an analysis of nationally representative data from the Medical Expenditure Panel Surveys from 2000 to 2010. Trends in population-based prescribing were examined for overall antibiotics, broad-spectrum antibiotics, antibiotics for acute respiratory tract infections (ARTIs) and antibiotics prescribed during ARTI visits. Rates were reported for three age groups: children and adolescents (<18 years), adults (18 to 64 years), and older adults (≥65 years). An estimated 1.4 billion antibiotics were dispensed over the study period. Overall antibiotic prescribing decreased 18% (risk ratio (RR) 0.82, 95% confidence interval (95% CI) 0.72 to 0.94) among children and adolescents, remained unchanged for adults, and increased 30% (1.30, 1.14 to 1.49) among older adults. Rates of broad-spectrum antibiotic prescriptions doubled from 2000 to 2010 (2.11, 1.81 to 2.47). Proportions of broad-spectrum antibiotic prescribing increased across all age groups: 79% (1.79, 1.52 to 2.11) for children and adolescents, 143% (2.43, 2.07 to 2.86) for adults and 68% (1.68, 1.45 to 1.94) for older adults. ARTI antibiotic prescribing decreased 57% (0.43, 0.35 to 0.52) among children and adolescents and 38% (0.62, 0.48 to 0.80) among adults; however, it remained unchanged among older adults. While the number of ARTI visits declined by 19%, patients with ARTI visits were more likely to receive an antibiotic (73% versus 64%; P <0.001) in 2010 than in 2000. Antibiotic use has decreased among children and adolescents, but has increased for older adults. Broad-spectrum antibiotic prescribing continues to be on the rise. Public policy initiatives to promote the judicious use of antibiotics should continue and programs targeting older adults should be developed.
TL;DR: The epidemiology of multimorbidity in southern China was examined in a large representative sample and was associated with the regular use of secondary outpatient care in preference to primary care, which has many major implications.
Abstract: Background: China, like other countries, is facing a growing burden of chronic disease but the prevalence of multimorbidity and implications for the healthcare system have been little researched. We examined the epidemiology of multimorbidity in southern China in a large representative sample. The effects of multimorbidity and other factors on usual source of healthcare were also examined. Methods: We conducted a large cross-sectional survey among approximately 5% (N = 162,464) of the resident population in three prefectures in Guangdong province, southern China in 2011. A multistage, stratified random sampling was adopted. The study population had many similar characteristics to the national census population. Interviewer-administered questionnaires were used to collect self-report data on demographics, socio-economics, lifestyles, healthcare use, and health characteristics from paper-based medical reports. Results: More than one in ten of the total study population (11.1%, 95% confidence interval (CI) 10.6 to 11.6) had two or more chronic conditions from a selection of 40 morbidities. The prevalence of multimorbidity increased with age (adjusted odds ratio (aOR) = 1.36, 95% CI 1.35 to 1.38 per five years). Female gender (aOR = 1.70, 95% CI 1.64 to 1.76), low education (aOR = 1.26, 95% CI 1.23 to 1.29), lack of medical insurance (aOR = 1.79, 95% CI 1.71 to 1.89), and unhealthy lifestyle behaviours were independent predictors of multimorbidity. Multimorbidity was associated with the regular use of secondary outpatient care in preference to primary care. Conclusions: Multimorbidity is now common in China. The reported preferential use of secondary care over primary care by patients with multimorbidity has many major implications. There is an urgent need to further develop a strong and equitable primary care system.
TL;DR: An FI based on routine laboratory data can identify older adults at increased risk of death, and additional evaluation of this approach in clinical settings is warranted.
Abstract: Older adults are at an increased risk of death, but not all people of the same age have the same risk. Many methods identify frail people (that is, those at increased risk) but these often require time-consuming interactions with health care providers. We evaluated whether standard laboratory tests on their own, or added to a clinical frailty index (FI), could improve identification of older adults at increased risk of death. This is a secondary analysis of a prospective cohort study, where community dwelling and institutionalized participants in the Canadian Study of Health and Aging who also volunteered for blood collection (n = 1,013) were followed for up to six years. A standard FI (FI-CSHA) was constructed from data obtained during the clinical evaluation and a second, novel FI was constructed from laboratory data plus systolic and diastolic blood pressure measurements (FI-LAB). A combined FI included all items from each index. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves. Of 1,013 participants, 51.3% had died by six years. The mean baseline value of the FI-LAB was 0.27 (standard deviation 0.11; range 0.05 to 0.63), the FI-CSHA was 0.25 (0.11; 0.02 to 0.72), and the combined FI was 0.26 (0.09; 0.06 to 0.59). In an age- and sex-adjusted model, with each increment in the FI-LAB, the hazard ratios increased by 2.8% (95% confidence interval 1.02 to 1.04). The hazard ratios for the FI-CSHA and the combined FI were 1.02 (1.01 to 1.03) and 1.04 (1.03 to 1.05), respectively. The FI-LAB and FI-CSHA remained independently associated with death in the face of the other. The areas under the ROC curves were 0.72 for FI-LAB, 0.73 for FI-CSHA and 0.74 for the combined FI. An FI based on routine laboratory data can identify older adults at increased risk of death. Additional evaluation of this approach in clinical settings is warranted.
TL;DR: While theNumber of deceased donors is higher than the number of living donors, opt-out consent leads to a relative increase in the total number of livers and kidneys transplanted.
Abstract: Policy decisions about opt-in and opt-out consent for organ donation are based on limited evidence. To fill this gap we investigated the difference between deceased and living organ donation rates in opt-in and opt-out consent systems across a 13 year period. We controlled for extensive covariates and estimated the causal effect of consent with instrumental variables analysis. This panel study used secondary data analysis to compare organ donor and transplant rates in 48 countries that had either opt-in or opt-out consent. Organ donation data were obtained over a 13-year period between 2000 and 2012. The main outcome measures were the number of donors, number of transplants per organ and total number (deceased plus living) of kidneys and livers transplanted. The role of consent on donor and transplant rates was assessed using multilevel modeling and the causal effect estimated with instrumental variables analysis. Deceased donor rates (per-million population) were higher in opt-out (M = 14.24) than opt-in consent countries (M = 9.98; χ = -4.27, 95% confidence interval (CI) = -8.08, -0.45, P = .029). However, the number of living donors was higher in opt-in (M = 9.36) than opt-out countries (M = 5.49; B = 3.86, 95% CI = 1.16, 6.56, P = .006). Importantly, the total number of kidneys transplanted (deceased plus living) was higher in opt-out (M = 28.32) than opt-in countries (M = 22.43; B = -5.89, 95% CI = -11.60, -0.17, P = .044). Similarly, the total number of livers transplanted was higher in opt-out (M = 11.26) than opt-in countries (M = 7.53; B = -3.73, 95% CI = -7.47, 0.01, P = .051). Instrumental variables analysis suggested that the effect of opt-in versus opt-out consent on the difference between deceased and living donor rates is causal. While the number of deceased donors is higher than the number of living donors, opt-out consent leads to a relative increase in the total number of livers and kidneys transplanted.
TL;DR: A systematic review of the Medline and EMBASE databases supports the association of a number of traditional vascular risk factors, but also highlights disparities between clinically apparent and silent strokes, potentially suggesting important differences in pathophysiology and warranting further investigation.
Abstract: Background
Cerebral infarction is a commonly observed radiological finding in the absence of corresponding, clinical symptomatology, the so-called silent brain infarction (SBI). SBIs are a relatively new consideration as improved imaging has facilitated recognition of their occurrence. However, the true incidence, prevalence and risk factors associated with SBI remain controversial.
Max Delbrück Center for Molecular Medicine1, International Agency for Research on Cancer2, Imperial College London3, Utrecht University4, Emory University5, French Institute of Health and Medical Research6, German Cancer Research Center7, Aarhus University8, University of Granada9, University of Cambridge10, Cancer Epidemiology Unit11, Academy of Athens12, National and Kapodistrian University of Athens13, Harvard University14, Prevention Institute15, Umeå University16, Lund University17, University of Tromsø18
TL;DR: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles and prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
Abstract: Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors – healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index.
TL;DR: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes, with no significant associations apparent in the rest.
Abstract: Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR)=0.63; 95% CI 0.41 to 0.97; P for trend =0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend=0.04 and HR= 0.60; 95% CI 0.37 to 0.97; P for trend =0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.
TL;DR: High quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs, according to a systematic review and meta-analyses.
Abstract: Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.
TL;DR: There is good quality evidence that universally delivered workplace mental health interventions can reduce the level of depression symptoms among workers, and more evidence for the effectiveness of CBT-based programs than other interventions.
Abstract: Depression is a major public health problem among working-age adults. The workplace is potentially an important location for interventions aimed at preventing the development of depression, but to date, the mental health impact of universal interventions in the workplace has been unclear. A systematic search was conducted in relevant databases to identify randomized controlled trials of workplace interventions aimed at universal prevention of depression. The quality of studies was assessed using the Downs and Black checklist. A meta-analysis was performed using results from studies of adequate methodological quality, with pooled effect size estimates obtained from a random effects model. Nine workplace-based randomized controlled trials (RCT) were identified. The majority of the included studies utilized cognitive behavioral therapy (CBT) techniques. The overall standardized mean difference (SMD) between the intervention and control groups was 0.16 (95% confidence interval (CI): 0.07, 0.24, P = 0.0002), indicating a small positive effect. A separate analysis using only CBT-based interventions yielded a significant SMD of 0.12 (95% CI: 0.02, 0.22, P = 0.01). There is good quality evidence that universally delivered workplace mental health interventions can reduce the level of depression symptoms among workers. There is more evidence for the effectiveness of CBT-based programs than other interventions. Evidence-based workplace interventions should be a key component of efforts to prevent the development of depression among adults.