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Inflammation is a critical pathway in the pathogenesis of atherosclerosis. Previous studies have shown that plasma levels of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, are associated with cardiovascular disease independent of traditional risk factors. Randomized trial data have also shown that statins reduce not only hsCRP but also cardiovascular event rates independent of their effect on low-density lipoprotein cholesterol (LDL-C) level. More recently, the CANTOS trial showed that directly reducing inflammation with canakinumab, an interleukin (IL)-1β neutralizing monoclonal antibody, could also reduce cardiovascular event rates. These mark the first phase 3 trial results validating inflammation as a viable target for preventing cardiovascular disease. In this review, we recap the role of inflammation in cardiovascular disease and highlight previous trial data showing its modulation with statins and other agents. We also detail the CANTOS trial results and discuss its implications for clinicians as well as future directions for anti-inflammatory therapy in the prevention of cardiovascular disease.

Statins have been shown to induce a phosphoprotein signature that modifies MYC (myelocytomatosis viral oncogene) activation and to have anti‐inflammatory activity that may impact the risk of Non‐Hodgkin's lymphoma (NHL). We analyzed the relationship between statins and risk of NHL using data from the Women's Health Initiative (WHI). The study population included 161,563 postmenopausal women ages 50–79 years from which 712 cases of NHL were diagnosed after 10.8 years of follow‐up. Information on statin use and other risk factors was collected by self‐ and interviewer‐administered questionnaires. Multivariable‐adjusted HR and 95% CI evaluating the relationship between statin use at baseline, as well as in a time‐dependent manner and risk of NHL, were computed from Cox proportional hazards analyses. A separate analysis was performed for individual NHL subtypes: diffuse large B‐Cell lymphoma (DLBCL) (n = 228), follicular lymphoma (n = 169), and small lymphocytic lymphoma (n = 74). All statistical tests were two‐sided. There was no significant association between use of statins at baseline and risk of NHL (HR 0.85, 95% C.I. 0.67–1.08). However, in the multivariable‐adjusted time‐dependent models, statin use was associated with a borderline lower risk of NHL (HR 0.81, 95% C.I. 0.66–1.00). Considering subtypes of NHL, statin use was associated with a lower risk of DLBCL (HR 0.62, 95% C.I. 0.42–0.91). This effect was driven by lipophilic statins (HR 0.62, 95% C.I. 0.40–0.96). In the WHI, statins were associated with a lower overall risk of DLBCL, particularly attributable to lipophilic statins. These results may have impact on primary or secondary prevention of NHL, particularly DLBCL.

HIV pre-exposure prophylaxis (PrEP) is highly efficacious at preventing HIV acquisition. This review discusses ways to identify candidates for PrEP, recommended PrEP regimens, baseline and follow-up evaluations, applications of PrEP for HIV-serodiscordant couples, resources to address financial barriers, investigational strategies for PrEP, and educational resources for clinicians and patients.

The driving force behind the current global type 2 diabetes epidemic is insulin resistance in overweight and obese individuals. Dietary factors, physical inactivity, and sedentary behaviors are the major modifiable risk factors for obesity. Nevertheless, many overweight/obese people do not develop diabetes and lifestyle interventions focused on weight loss and diabetes prevention are often ineffective. Traditionally, chronically elevated blood glucose concentrations have been the hallmark of diabetes; however, many individuals will either remain ‘prediabetic’ or regress to normoglycemia. Thus, there is a growing need for innovative strategies to tackle diabetes at scale. The emergence of biomarker technologies has allowed more targeted therapeutic strategies for diabetes prevention (precision medicine), though largely confined to pharmacotherapy. Unlike most drugs, lifestyle interventions often have systemic health-enhancing effects. Thus, the pursuance of lifestyle precision medicine in diabetes seems rational. Herein, we review the literature on lifestyle interventions and diabetes prevention, describing the biological systems that can be characterized at scale in human populations, linking them to lifestyle in diabetes, and consider some of the challenges impeding the clinical translation of lifestyle precision medicine. Electronic supplementary material The online version of this article (doi:10.1186/s12916-017-0938-x) contains supplementary material, which is available to authorized users.

Background: Levels of LDL (low‐density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid‐related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. Methods and Results: We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low‐density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo‐allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non–high‐density lipoprotein cholesterol, and triglycerides, but not LDL‐c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On‐statin levels of the smallest VLDL particle subclass were associated with a 68% per‐SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk—this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C‐index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein‐related risk were observed. Conclusions: Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Background: Inflammation is suggested to be a central feature of atherosclerosis, particularly among smokers. We studied whether inflammatory biomarkers GlycA and high‐sensitivity C‐reactive protein are associated with cigarette smoking. Methods and Results: A total of 11 509 participants, 6774 from the MESA (Multi‐Ethnic Study of Atherosclerosis) and 4735 from ELSA‐Brasil (The Brazilian Longitudinal Study of Adult Health) were included. We evaluated the cross‐sectional association between multiple measures of smoking behavior and the inflammatory biomarkers, GlycA and high‐sensitivity C‐reactive protein, using regression models adjusted for demographic, anthropometric, and clinical characteristics. Participants were 57.7±11.1 years old and 46.4% were men. Never, former, and current smokers comprised 51.7%, 34.0%, and 14.3% of the population, respectively. Multivariable‐adjusted mean absolute difference in GlycA levels (μmol/L) with 95% confidence interval (CI) were higher for former (4.1, 95% CI, 1.7–6.6 μmol/L) and current smokers (19.9, 95% CI, 16.6–23.2 μmol/L), compared with never smokers. Each 5‐unit increase in pack‐years of smoking was associated with higher GlycA levels among former (0.7, 95% CI, 0.3–1.1 μmol/L) and current smokers (1.6, 95% CI, 0.8–2.4 μmol/L). Among former smokers, each 5‐year increase in time since quitting smoking was associated with lower GlycA levels (−1.6, 95% CI, −2.4 to −0.8 μmol/L) and each 10‐unit increase in number of cigarettes/day was associated with higher GlycA among current smokers (2.8, 95% CI, 0.5–5.2 μmol/L). There were similar significant associations between all measures of smoking behavior, and both log‐transformed GlycA and high‐sensitivity C‐reactive protein. Conclusions: Acute and chronic exposure to tobacco smoking is associated with inflammation, as quantified by both GlycA and high‐sensitivity C‐reactive protein. These biomarkers may have utility for the study and regulation of novel and traditional tobacco products.

There are ~900,000 new HIV infections among women every year, representing nearly half of all new HIV infections globally. In the US, nearly one-fifth of all new HIV infections occur among women, and women from racial and ethnic minority communities experience disproportionately high rates of new HIV infections. Thus, there is a need to develop and implement effective HIV prevention strategies for women in the US and internationally, with a specific need to advance strategies in minority communities. Previous studies have demonstrated that oral HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral medications by HIV-uninfected persons to prevent HIV acquisition, can reduce HIV incidence among women who are adherent to PrEP. However, to date, awareness and uptake of PrEP among women have been very limited, suggesting a need for innovative strategies to increase the knowledge of and access to PrEP among women in diverse settings. This narrative review summarizes the efficacy and safety data of PrEP in women, discusses considerations related to medication adherence for women who use PrEP, and highlights behavioral, social, and structural barriers to maximize the effectiveness of PrEP in women. It also reviews novel modalities for PrEP in women which are being developed and tested, including topical formulations and long-acting injectable agents that may offer advantages as compared to oral PrEP and proposes a community-oriented, social networking framework to increase awareness of PrEP among women. If women are provided with access to PrEP and support to overcome social and structural barriers to adhere to PrEP, this prevention strategy holds great promise to impact the HIV epidemic among women in the US and globally.

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider’s office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider’s office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Global economic impacts of epidemics suggest high return on investment in prevention and One Health capacity. However, such investments remain limited, contributing to persistent endemic diseases and vulnerability to emerging ones. An interdisciplinary workshop explored methods for country-level analysis of added value of One Health approaches to disease control. Key recommendations include: 1. systems thinking to identify risks and mitigation options for decision-making under uncertainty; 2. multisectoral economic impact assessment to identify wider relevance and possible resource-sharing, and 3. consistent integration of environmental considerations. Economic analysis offers a congruent measure of value complementing diverse impact metrics among sectors and contexts.

Background: Primary prevention of cardiovascular disease (CVD) focuses on treatment of risk factors, including hypercholesterolemia, hypertension, and type 2 diabetes mellitus. We investigated whether a healthy diet in adolescence prevents development of clinical risk factors or incidence of CVD in adulthood. Methods and Results: We examined the time to the first development of ≥1 clinical risk factor (hypercholesterolemia, hypertension, or type 2 diabetes mellitus) or CVD in relation to a high school Alternative Healthy Eating Index (HS‐AHEI) within the Nurses’ Health Study II. Among those who completed a food frequency questionnaire about their high school diet and adult diet (mean age 42 years), 27 406 women free of clinical risk factors and 42 112 women free of CVD in 1998 were followed to June 2011. Hazard ratios (HRs) and 95% CIs were adjusted for potential confounders in high school and adulthood. We documented 11 542 first diagnoses of clinical risk factors and 423 CVD events. The HS‐AHEI was associated with a lower rate of risk factors (HR highest versus lowest quintiles 0.82; 95% CI, 0.77–0.87 [P trend <0.001]), was inversely associated with risk of developing ≥1 clinical risk factor in women with a low, medium, and high AHEI score during adulthood (HR high HS‐AHEI/high adult AHEI versus low/low 0.79 [95% CI, 0.74–0.85]), but was not statistically significantly associated with incident CVD. Conclusions: A healthy diet during adolescence is associated with lower risk of developing CVD risk factors. As diet tracks throughout life, and adult diet prevents CVD, healthy dietary habits that begin early are important for primordial prevention of CVD.

Background: Diagnostic testing in the care of patients newly presenting with symptoms suggestive of coronary artery disease may influence risk factor management, independent of test type or test results. However, little is known about changes in medications and lifestyle after anatomical or functional testing. Methods and Results: We examined what factors influenced preventive medical therapy and lifestyle practices at 60 days among 10 003 symptomatic patients (53% women; mean age 61 years) randomly assigned to anatomical testing with coronary computed tomographic angiography or functional testing (NCT01174550). We also assessed the association of preventive changes with major cardiovascular events. There were no differences in medications/lifestyle at baseline. At 60 days, relative to baseline, the computed tomographic angiography strategy was associated with a higher proportion of patients newly initiating aspirin (11.8% versus 7.8%), statins (12.7% versus 6.2%), and β‐blockers (8.1% versus 5.3%), compared to functional testing (P<0.0001 for each). No significant differences between computed tomographic angiography and functional testing strategies were observed for initiation of exercise, quitting smoking, or weight loss in overweight/obese patients, though overall prevalence of healthy eating was higher after computed tomographic angiography (P=0.002) while obese/overweight status was lower (P=0.040). Positive initial test results and revascularization demonstrated stronger associations with preventive medications and lifestyle than test type. Medication initiation was not associated with fewer cardiovascular events. Conclusions: Positive initial test results and revascularization are primary drivers of changes in preventive medical and lifestyle practices, with test type making secondary contributions. However, substantial opportunities exist to further reduce cardiovascular risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Transgender (trans) communities worldwide, particularly those on the trans feminine spectrum, are disproportionately burdened by HIV infection and at risk for HIV acquisition/transmission. Trans individuals represent an underserved, highly stigmatized, and under-resourced population not only in HIV prevention efforts but also in delivery of general primary medical and clinical care that is gender affirming. We offer a model of gender-affirmative integrated clinical care and community research to address and intervene on disparities in HIV infection for transgender people. We define trans terminology, briefly review the social epidemiology of HIV infection among trans individuals, highlight gender affirmation as a key social determinant of health, describe exemplar models of gender-affirmative clinical care in Boston MA, New York, NY, and San Francisco, CA, and offer suggested “best practices” for how to integrate clinical care and research for the field of HIV prevention. Holistic and culturally responsive HIV prevention interventions must be grounded in the lived realities the trans community faces to reduce disparities in HIV infection. HIV prevention interventions will be most effective if they use a structural approach and integrate primary concerns of transgender people (eg, gender-affirmative care and management of gender transition) alongside delivery of HIV-related services (eg, biobehavioral prevention, HIV testing, linkage to care, and treatment).

Introduction: Transgender populations have been underrepresented in HIV epidemiologic studies and consequently in HIV prevention, care, and treatment programs. Since 2012, there has been a dramatic increase in research focused on transgender people. Studies highlight the burden of HIV and risk determinants, including intersecting stigmas, as drivers of syndemics among transgender populations. This review synthesizes the most recent global epidemiology of HIV infection and describes current gaps in research and interventions to inform prioritization of HIV research for transgender populations. Methods: A systematic review was conducted of the medical literature published between January 1, 2012 and November 30, 2015. The data focused on HIV prevalence, determinants of risk, and syndemics among transgender populations. Results: Estimates varied dramatically by location and subpopulation. Transfeminine individuals have some of the highest concentrated HIV epidemics in the world with laboratory-confirmed prevalence up to 40%. Data were sparse among trans masculine individuals; however, they suggest potential increased risk for trans masculine men who have sex with men (MSM). No prevalence data were available for transgender people across Sub-Saharan Africa or Eastern Europe/Central Asia. Emerging data consistently support the association of syndemic conditions with HIV risk in transgender populations. Discussion: Addressing syndemic conditions and gender-specific challenges is critical to ensure engagement and retention in HIV prevention by transgender populations. Future research should prioritize: filling knowledge gaps in HIV epidemiology; elucidating how stigma shapes syndemic factors to produce HIV and other deleterious effects on transgender health; and understanding how to effectively implement HIV interventions for transgender people.

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer’s and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer’s Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

Background: The coverage of prevention and treatment strategies for ischemic heart disease and stroke is very low in Ethiopia. In view of Ethiopia’s meager healthcare budget, it is important to identify the most cost-effective interventions for further scale-up. This paper’s objective is to assess cost-effectiveness of prevention and treatment of ischemic heart disease (IHD) and stroke in an Ethiopian setting. Methods: Fifteen single interventions and sixteen intervention packages were assessed from a healthcare provider perspective. The World Health Organization’s Choosing Interventions that are Cost-Effective model for cardiovascular disease was updated with available country-specific inputs, including demography, mortality and price of traded and non-traded goods. Costs and health benefits were discounted at 3 % per year. Incremental cost-effectiveness ratios are reported in US$ per disability adjusted life year (DALY) averted. Sensitivity analysis was undertaken to assess robustness of our results. Results: Combination drug treatment for individuals having >35 % absolute risk of a CVD event in the next 10 years is the most cost-effective intervention. This intervention costs US$67 per DALY averted and about US$7 million annually. Treatment of acute myocardial infarction (AMI) (costing US$1000–US$7530 per DALY averted) and secondary prevention of IHD and stroke (costing US$1060–US$10,340 per DALY averted) become more efficient when delivered in integrated packages. At an annual willingness-to-pay (WTP) level of about US$3 million, a package consisting of aspirin, streptokinase, ACE-inhibitor and beta-blocker for AMI has the highest probability of being most cost-effective, whereas as WTP increases to > US$7 million, combination drug treatment to individuals having >35 % absolute risk stands out as the most cost-effective strategy. Cost-effectiveness ratios were relatively more sensitive to halving the effectiveness estimates as compared with doubling the price of drugs and laboratory tests. Conclusions: In Ethiopia, the escalating burden of CVD and its risk factors warrants timely action. We have demonstrated that selected CVD intervention packages could be scaled up at a modest budget increase. The level of willingness-to-pay has important implications for interventions’ probability of being cost-effective. The study provides valuable evidence for setting priorities in an essential healthcare package for CVD in Ethiopia.

Modifiable lifestyle factors, such as obesity, lack of physical activity, and smoking, contribute greatly to cancer and chronic disease morbidity and mortality worldwide. This review appraises recent evidence on modifiable lifestyle factors in the prevention of endometrial cancer (EC) and ovarian cancer (OC) as well as new evidence for lifestyle management of EC and OC survivors. For EC, obesity continues to be the strongest risk factor, while new evidence suggests that physical activity, oral contraceptive pills, and bariatric surgery may be protective against EC. Other medications, such as metformin and nonsteroidal anti-inflammatory drugs, may be protective, and interventional research is ongoing. For OC, we find increasing evidence to support the hypothesis that obesity and hormone replacement therapy increase the risk of developing OC. Oral contraceptive pills are protective against OC but are underutilized. Dietary factors such as the Mediterranean diet and alcohol consumption do not seem to affect the risk of either OC or EC. For EC and OC survivors, physical activity and weight loss are associated with improved quality of life. Small interventional trials show promise in increasing physical activity and weight maintenance for EC and OC survivors, although the impact on long-term health, including cancer recurrence and overall mortality, is unknown. Women’s health providers should integrate counseling about these modifiable lifestyle factors into both the discussion of prevention for all women and the management of survivors of gynecologic cancers.

Background: Insecticide-treated bed nets (ITNs) are highly effective in reducing malaria burden when used properly. However, factors related to individuals, households and community may influence how ITNs are used for malaria control. The study examined influences exerted at these levels to determine if they are associated with ITN non-use among children under 5 years of age in Rwanda. Methods: Using data from the 2010 Rwanda Demographic Health Survey, the investigation was done on the factors associated with ITN non-use among children under 5 years. Descriptive statistics as well as univariate and multilevel logistic regression analyses were used to identify factors associated with ITN non-use. Results: Responses from a total of 6173 women aged 15–49 years living in 492 villages were included in the analysis. Risk factors for children not utilizing ITNs (25 %) included: (Odds ratio [95 % confidence interval]) households with more than five members (1.42 [1.23–1.63]), employed mother (1.33 [1.06–1.66]), and lower household altitude (1.36 [1.14–1.61]). Protective risk factors for ITN use included households with more than three nets (0.39 [0.33–0.47]), mothers who attended one to four visits at antenatal clinics during pregnancy (0.45 [0.29–0.69]), more than four antenatal clinic visits during pregnancy (0.39 [0.21–0.70]), mothers married or living with partner (0.43 [0.36–0.52]), mothers with any education level (0.77 [0.65–0.91]), and households with higher community wealth quintile (0.71 [0.59–0.84]). Conclusions: Rwanda has achieved high coverage of ITN use and proper use has contributed to a decline in malaria in Rwanda; however, maintaining universal ITN coverage is not enough to protect citizens from this disease. Risk factors related to ITN non-use at individual, household and community level include poverty, education, birth spacing, and antenatal clinic attendance. There is a need to address findings with strategies to mitigate the non-use of ITNs for effective malaria prevention in Rwanda.

Background: People with bipolar disorder (BD) have a mortality gap of up to 20 years compared to the general population. Physical conditions, such as cardiovascular disease (CVD) and cancer, cause the majority of excess deaths in psychiatric populations and are the leading causes of mortality in people with BD. However, comparatively little attention has been paid to reducing the risk of physical conditions in psychiatric populations. Unhealthy lifestyle behaviors are among the potentially modifiable risk factors for a range of commonly comorbid chronic medical conditions, including CVD, diabetes, and obesity. This systematic review will identify and evaluate the available evidence for effective interventions to reduce risk and promote healthy lifestyle behaviors in BD. Methods/design We will search MEDLINE, Embase, PsychINFO, Cochrane Database of Systematic Reviews, and CINAHL for published research studies (with at least an abstract published in English) that evaluate behavioral or psychosocial interventions to address the following lifestyle factors in people with BD: tobacco use, physical inactivity, unhealthy diet, overweight or obesity, sleep-wake disturbance, and alcohol/other drug use. Primary outcomes for the review will be changes in tobacco use, level of physical activity, diet quality, sleep quality, alcohol use, and illicit drug use. Data on each primary outcome will be synthesized across available studies in that lifestyle area (e.g., tobacco abstinence, cigarettes smoked per day), and panel of research and clinical experts in each of the target lifestyle behaviors and those experienced with clinical and research with individuals with BD will determine how best to represent data related to that primary outcome. Seven members of the systematic review team will extract data, synthesize the evidence, and rate it for quality. Evidence will be synthesized via a narrative description of the behavioral interventions and their effectiveness in improving the healthy lifestyle behaviors in people with BD. Discussion The planned review will synthesize and evaluate the available evidence regarding the behavioral or psychosocial treatment of lifestyle-related behaviors in people with BD. From this review, we will identify gaps in our existing knowledge and research evidence about the management of unhealthy lifestyle behaviors in people with BD. We will also identify potential opportunities to address lifestyle behaviors in BD, with a view to reducing the burden of physical ill-health in this population. Systematic review registration PROSPERO CRD42015019993 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0282-9) contains supplementary material, which is available to authorized users.

Background: Warfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke‐preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range (TTR) ≥70% is similarly as effective and safe as novel anticoagulants. It is unclear whether AF patients with TTR ≥70% will remain stably anticoagulated and avoid the need to switch to a novel anticoagulant. We assessed stability of warfarin anticoagulation in AF patients with an initial TTR ≥70%. Methods and Results: Within the community‐based Anticoagulation and Risk Factors in AF (ATRIA) cohort followed from 1996 to 2003, we identified 2841 new warfarin users who continued warfarin over 9 months. We excluded months 1 to 3 to achieve a stable dose. For the 987 patients with TTR ≥70% in an initial 6‐month period (TTR 1; months 4–9), we described the distribution of TTR 2 (months 10–15) and assessed multivariable correlates of persistent TTR ≥70%. Of patients with TTR 1 ≥70%, 57% persisted with TTR 2 ≥70% and 16% deteriorated to TTR 2 <50%. Only initial TTR 1 ≥90% (adjusted odds ratio 1.47, 95% CI 1.07–2.01) independently predicted TTR 2 ≥70%. Heart failure was moderately associated with marked deterioration (TTR 2 <50%); adjusted odds ratio 1.45, 95% CI 1.00–2.10. Conclusions: Nearly 60% of AF patients with high‐quality TTR1 on warfarin maintained TTR ≥70% over the next 6 months. A minority deteriorated to very poor TTR. Patient features did not strongly predict TTR in the second 6‐month period. Our analyses support watchful waiting for AF patients with initial high‐quality warfarin anticoagulation before considering alternative anticoagulants.

Background: Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD. Methods and Results: We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort. Conclusions: Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD.

Introduction: HIV incidence remains high among young women in sub-Saharan Africa in spite of scale-up of HIV testing, behavioural interventions, antiretroviral treatment and medical male circumcision. There is a critical need to critique past approaches and learn about the most effective implementation of evidence-based HIV prevention strategies, particularly emerging interventions such as pre-exposure prophylaxis (PrEP). Discussion Women in sub-Saharan Africa are at increased risk of HIV during adolescence and into their 20s, in part due to contextual factors including gender norms and relationship dynamics, and limited access to reproductive and sexual health services. We reviewed behavioural, behavioural economic and biomedical approaches to HIV prevention for young African women, with a particular focus on the barriers, opportunities and implications for implementing PrEP in this group. Behavioural interventions have had limited impact in part due to not effectively addressing the context, broader sexual norms and expectations, and structural factors that increase risk and vulnerability. Of biomedical HIV prevention strategies that have been tested, daily oral PrEP has the greatest evidence for protection, although adherence was low in two placebo-controlled trials in young African women. Given high efficacy and effectiveness in other populations, demonstration projects of open-label PrEP in young African women are needed to determine the most effective delivery models and whether women at substantial risk are motivated and able to use oral PrEP with sufficient adherence to achieve HIV prevention benefits. Conclusions: Social marketing, adherence support and behavioural economic interventions should be evaluated as part of PrEP demonstration projects among young African women in terms of their effectiveness in increasing demand and optimizing uptake and effective use of PrEP. Lessons learned through evaluations of implementation strategies for delivering oral PrEP, a first-generation biomedical HIV prevention product, will inform development of new and less user-dependent PrEP formulations and delivery of an expanding choice of prevention options in HIV prevention programmes for young African women.

Background: The proportion of women entering pregnancy overweight or obese has been rising and, in turn, is associated with adverse maternal and fetal outcomes. Gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines further increases health risks and has been independently associated with postpartum weight retention. Hispanic women are disproportionately affected by overweight and obesity, but have had limited access to interventions that promote healthy lifestyles due to cultural, socioeconomic, and language barriers. Therefore, the overall goal of this randomized controlled trial is to test the efficacy of a culturally and linguistically modified, individually-tailored lifestyle intervention to reduce excess GWG, increase postpartum weight loss, and improve maternal metabolic status among overweight/obese Hispanic women. Methods/Design Overweight/obese Hispanic women are recruited in early pregnancy and randomly assigned to a Lifestyle Intervention (n = 150) or a Comparison Health and Wellness (control) intervention (n = 150). Multimodal contacts (i.e., in-person, telephone counseling, and mailed print-based materials) are used to deliver the intervention from early pregnancy (12 weeks gestation) to 6 months postpartum, with follow-up to 1 year postpartum. Targets of the intervention are to achieve IOM Guidelines for GWG and postpartum weight loss; American Congress of Obstetrician and Gynecologist guidelines for physical activity; and American Diabetes Association guidelines for diet. The intervention draws from Social Cognitive Theory and the Transtheoretical Model and includes strategies to address the specific social, cultural, and economic challenges faced by low-income Hispanic women. Assessments are conducted at baseline (~10 weeks gestation), mid pregnancy (24–28 weeks gestation), late pregnancy (32–34 weeks gestation) and postpartum at 6-weeks, 6-months, and 12-months by bicultural and bilingual personnel blinded to the intervention arm. Efficacy is assessed via GWG, postpartum weight loss, and biomarkers of glycemic control, insulin resistance, and cardiovascular disease risk factors. Changes in physical activity and diet are measured via 7-day accelerometer data and 24-h dietary recalls at each assessment time period. Discussion Hispanic women are the fastest growing minority group in the U.S. and are disproportionately affected by overweight and obesity. This randomised trial uses a high-reach, low-cost strategy that can readily be translated into clinical practice in underserved and minority populations. Trial registration NCT01868230 May 29, 2013

Background: The high prevalence of major depressive disorder in adolescents and the low rate of successful treatment highlight a pressing need for accessible, affordable adolescent depression prevention programs. The Internet offers opportunities to provide adolescents with high quality, evidence-based programs without burdening or creating new care delivery systems. Internet-based interventions hold promise, but further research is needed to explore the efficacy of these approaches and ways of integrating emerging technologies for behavioral health into the primary care system. Methods/Design We developed a primary care Internet-based depression prevention intervention, Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training (CATCH-IT), to evaluate a self-guided, online approach to depression prevention and are conducting a randomized clinical trial comparing CATCH-IT to a general health education Internet intervention. This article documents the research framework and randomized clinical trial design used to evaluate CATCH-IT for adolescents, in order to inform future work in Internet-based adolescent prevention programs. The rationale for this trial is introduced, the current status of the study is reviewed, and potential implications and future directions are discussed. Discussion The current protocol represents the only current, systematic approach to connecting at-risk youth with self-directed depression prevention programs in a medical setting. This trial undertakes the complex public health task of identifying at-risk individuals through mass screening of the general primary care population, rather than solely relying on volunteers recruited over the Internet, and the trial design provides measures of both symptomatic and diagnostic clinical outcomes. At the present time, we have enrolled N = 234 adolescents/expected 400 and N = 186 parents/expected 400 in this trial, from N = 6 major health systems. The protocol described here provides a model for a new generation of interventions that blend substantial computer-based instruction with human contact to intervene to prevent mental disorders such as depression. Because of the potential for broad generalizability of this model, the results of this study are important, as they will help develop the guidelines for preventive interventions with youth at-risk for the development of depressive and other mental disorders. Trial registration Clinical Trial Registry: NCT01893749 date 6 May 2012.

Background: In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results: We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions: TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767.

Background: Clinical practice focuses on the primary prevention of cardiovascular (CV) disease (CVD) through the modification and pharmacological treatment of elevated risk factors. Prediction models based on established risk factors are available for use in the primary prevention setting. However, the prevention of risk factor development through healthy lifestyle behaviors, or primordial prevention, is of paramount importance to achieve optimal population‐wide CV health and minimize long‐term CVD risk. Methods and Results: We developed a lifestyle‐based CVD prediction model among 61 025 women in the Nurses’ Health Study and 34 478 men in the Health Professionals Follow‐up Study, who were free of chronic disease in 1986 and followed for ≤24 years. Lifestyle factors were assessed by questionnaires in 1986. In the derivation step, we used the Bayes Information Criterion to create parsimonious 20‐year risk prediction models among a random two thirds of participants in each cohort separately. The scores were validated in the remaining one third of participants in each cohort. Over 24 years, there were 3775 cases of CVD in women and 3506 cases in men. The Healthy Heart Score included age, smoking, body mass index, exercise, alcohol, and a composite diet score. In the validation cohort, the risk score demonstrated good discrimination (Harrell's C‐index, 0.72; 95% confidence interval [CI], 0.71, 0.74 [women]; 0.77; 95% CI, 0.76, 0.79 [men]), fit, and calibration, particularly among individuals without baseline hypertension or hypercholesterolemia. Conclusions: The Healthy Heart Score accurately identifies individuals at elevated risk for CVD and may serve as an important clinical and public health screening tool for the primordial prevention of CVD.

OBJECTIVE To describe the metabolic profile of individuals with objective binge eating (OBE) and to evaluate whether associations between OBE and metabolic risk factors are mediated by body mass index (BMI). DESIGN AND METHODS Participants from the Framingham Heart Study, Third Generation and Omni 2 cohorts (n = 3551, 53.1% women, mean age 46.4 years) were screened for binge eating. We used multivariable-adjusted regression models to examine the associations of OBE with metabolic risk factors. RESULTS The prevalence of OBE was 4.8% in women and 4.9% in men. Compared to non-binge eating, OBE was associated with higher odds of hypertension (OR 1.85, 95% CI 1.32–2.60), hypertriglyceridemia (OR 1.42, 95% CI 1.01–2.01), low HDL (OR 1.70, 95% CI 1.18–2.44), insulin resistance (OR 3.18, 95% CI 2.25–4.50) and metabolic syndrome (OR 2.75, 95% CI 1.94–3.90). Fasting glucose was 7.2 mg/dl higher in those with OBE (p=0.0001). Individuals with OBE had more visceral, subcutaneous and liver fat. Most of these associations were attenuated with adjustment for BMI, with the exception of fasting glucose. CONCLUSIONS Binge eating is associated with a high burden of metabolic risk factors. Much of the associated risk appears to be mediated by BMI, with the exception of fasting glucose.

Acute pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). It is reported to occur in 2–10% of unselected patient samples and up to 40% of high-risk patients. The purpose of this article is to review the evidence behind the known risk factors for post-ERCP pancreatitis, as well as the technical and medical approaches developed to prevent it. There have been many advances in identifying the causes of this condition. Based on this knowledge, a variety of preventive strategies have been developed and studied. The approach to prevention begins with careful patient selection and performing ERCP for specific indications, while considering alternative diagnostic modalities when appropriate. Patients should also be classified by high-risk factors such as young age, female sex, suspected sphincter of Oddi dysfunction, a history of post-ERCP pancreatitis, and normal serum bilirubin, all of which have been identified in numerous research studies. The pathways of injury that are believed to cause post-ERCP pancreatitis eventually lead to the common endpoint of inflammation, and these individual steps can be targeted for preventive therapies through procedural techniques and medical management. This includes the use of a guide wire for cannulation, minimizing the number of cannulation attempts, avoiding contrast injections or trauma to the pancreatic duct, and placement of a temporary pancreatic duct stent in high-risk patients. Administration of rectal non-steroidal anti-inflammatory agents (NSAIDs) in high-risk patients is the proven pharmacological measure for prevention of post-ERCP pancreatitis. The evidence for or against numerous other attempted therapies is still unclear, and ongoing investigation is required.

Background: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. Methods: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. Results: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. Conclusions: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis.

The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom developed guidelines for the diagnosis, prevention, and management of delirium in July 2010 that included 10 recommendations for delirium prevention. The Hospital Elder Life Program (HELP) is a targeted multicomponent strategy that has proven effective and cost-effective at preventing functional and cognitive decline in hospitalized older persons. HELP provided much of the basis for seven of the NICE recommendations. Given interest by new HELP sites to meet NICE guidelines, three new protocols addressing hypoxia, infection, and pain that were not previously included in the HELP program were developed. In addition, the NICE dehydration guideline included constipation, which was not specifically addressed in the HELP protocols. This project describes the systematic development of three new protocols (hypoxia, infection, pain) and the expansion of an existing HELP protocol (constipation and dehydration) to achieve alignment between the HELP protocols and NICE guidelines. Following the Institute of Medicine recommendations for developing trustworthy guidelines, an interdisciplinary group of experts conducted a systematic review of current literature, rated the quality of the evidence, developed intervention protocols based on the highest-quality evidence, and submitted the protocols first to internal review and then to external review by an interdisciplinary panel of experts. The protocols were revised based on the review process and incorporated into the HELP materials. Inclusion of these protocols enhances the scope of the HELP program and allows fulfillment of NICE guideline recommendations for delirium prevention. The rigorous process applied may provide a useful example for updating existing guidelines or protocols that may be applicable to a broad range of clinical applications.

Background: The prevalence and health consequences of eating disorders and weight stigmatization have prompted increasing discussion of potential policy actions to address these public health issues. The present study aimed to assess support for policy strategies to address eating disorders and weight stigmatization among the general public and relevant health professionals. Methods: An Internet survey was fielded to a national sample of 944 US adults and 1,420 members of professional organizations specializing in eating disorders to examine their support for 23 potential policy strategies to address eating disorders and weight stigma. Participants also rated policy actions according to their potential for positive impact and feasible implementation. Results: Support for the majority of health and social policies was high in both samples. For example, strategies to 1) improve school-based health curriculum to include content aimed at preventing eating disorders, 2) require training for educators and health providers on the prevention and early identification of eating disorders, and 3) implement school-based anti-bullying policies that that protect students from being bullied about their weight, were supported by over two-thirds of participants. Conclusions: Our findings suggest that both health and social policy actions will be important in broader policy initiatives to address eating disorders and weight stigma.

Background: Armed conflicts are associated with a wide range of impacts on the mental health of children and adolescents. We evaluated the effectiveness of a school-based intervention aimed at reducing symptoms of posttraumatic stress disorder, depression, and anxiety (treatment aim); and improving a sense of hope and functioning (preventive aim). Methods: We conducted a cluster randomized trial with 329 children in war-affected Burundi (aged 8 to 17 (mean 12.29 years, standard deviation 1.61); 48% girls). One group of children (n = 153) participated in a 15-session school-based intervention implemented by para-professionals, and the remaining 176 children formed a waitlist control condition. Outcomes were measured before, one week after, and three months after the intervention. Results: No main effects of the intervention were identified. However, longitudinal growth curve analyses showed six favorable and two unfavorable differences in trajectories between study conditions in interaction with several moderators. Children in the intervention condition living in larger households showed decreases on depressive symptoms and function impairment, and those living with both parents showed decreases on posttraumatic stress disorder and depressive symptoms. The groups of children in the waitlist condition showed increases in depressive symptoms. In addition, younger children and those with low levels of exposure to traumatic events in the intervention condition showed improvements on hope. Children in the waitlist condition who lived on their original or newly bought land showed improvements in hope and function impairment, whereas children in the intervention condition showed deterioration on these outcomes. Conclusions: Given inconsistent effects across studies, findings do not support this school-based intervention as a treatment for posttraumatic stress disorder and depressive symptoms in conflict-affected children. The intervention appears to have more consistent preventive benefits, but these effects are contingent upon individual (for example, age, gender) and contextual (for example, family functioning, state of conflict, displacement) variables. Results suggest the potential benefit of school-based preventive interventions particularly in post-conflict settings. Trial registration The study was registered as ISRCTN42284825

Background: Diabetes and obesity have reached epidemic proportions in the U.S. with rates consistently higher among Hispanics as compared to non-Hispanic whites. Among Hispanic women diagnosed with gestational diabetes mellitus (GDM), 50% will go on to develop type 2 diabetes within 5 years of the index pregnancy. Although randomised controlled trials among adults with impaired glucose tolerance have shown that diet and physical activity reduce the risk of type 2 diabetes, such programs have not been tested in high-risk postpartum women. The overall goal of this randomised controlled trial is to test the efficacy of a culturally and linguistically modified, individually-tailored lifestyle intervention to reduce risk factors for type 2 diabetes and cardiovascular disease among postpartum Hispanic women with a history of abnormal glucose tolerance during pregnancy. Methods/Design Hispanic pregnant women who screen positive for GDM will be recruited and randomly assigned to a Lifestyle Intervention (n = 150) or a Health & Wellness (control) Intervention (n = 150). Multimodal contacts (i.e., in-person, telephone, and mailed materials) will be used to deliver the intervention from late pregnancy (29 weeks gestation) to 12 months postpartum. Targets of the intervention are to achieve Institute of Medicine Guidelines for postpartum weight loss; American Congress of Obstetrician and Gynecologist guidelines for physical activity; and American Diabetes Association guidelines for diet. The intervention draws from Social Cognitive Theory and the Transtheoretical Model and addresses the specific cultural and environmental challenges faced by low-income Hispanic women. Assessments will be conducted at enrollment, and at 6-weeks, 6-months, and 12-months postpartum by trained bicultural and bilingual personnel blinded to the intervention arm. Efficacy will be assessed via postpartum weight loss and biomarkers of insulin resistance and cardiovascular risk. Changes in physical activity and diet will be measured via 7-day actigraph data and three unannounced 24-hour dietary recalls at each assessment time period. Discussion Hispanic women are the fastest growing minority group in the U.S. and have the highest rates of sedentary behavior and postpartum diabetes after a diagnosis of GDM. This randomised trial uses a high-reach, low-cost strategy that can readily be translated into clinical practice in underserved and minority populations. Trial registration NCT01679210

Background The Hospital Elder Life Program (HELP) has been shown to be highly efficient and (cost-)effective in reducing delirium incidence in the USA. HELP provides multicomponent protocols targeted at specific risk factors for delirium and introduces a different view on care organization, with trained volunteers playing a pivotal role. The primary aim of this study is the quantification of the (cost-)effectiveness of HELP in the Dutch health care system. The second aim is to investigate the experiences of patients, families, professionals and trained volunteers participating in HELP. Methods/Design A multiple baseline approach (also known as a stepped-wedge design) will be used to evaluate the (cost-) effectiveness of HELP in a cluster randomized controlled study. All patients aged 70 years and older who are at risk for delirium and are admitted to cardiology, internal medicine, geriatrics, orthopedics and surgery at two participating community hospitals will be included. These eight units are implementing the intervention in a successive order that will be determined at random. The incidence of delirium, the primary outcome, will be measured with the Confusion Assessment Method (CAM). Secondary outcomes include the duration and severity of delirium, quality of life, length of stay and the use of care services up to three months after hospital discharge. The experiences of patients, families, professionals and volunteers will be investigated using a qualitative design based on the grounded theory approach. Professionals and volunteers will be invited to participate in focus group interviews. Additionally, a random sample of ten patients and their families from each hospital unit will be interviewed at home after discharge. Discussion We hypothesize that HELP will reduce delirium incidence during hospital admission and decrease the duration and severity of delirium and length of hospital stays among these older patients, which will lead to reduced health care costs. The results of this study may fundamentally change our views on care organization for older patients at risk for delirium. The stepped-wedge design was chosen for ethical, practical and statistical reasons. The study results will be generalizable to the Dutch hospital care system, and the proven cost-effectiveness of HELP will encourage the spread and implementation of this program.

The incidence and severity of Clostridium difficile infection (CDI) have dramatically increased in the Western world in recent years. In contrast, CDI is rarely reported in China, possibly due to under-diagnosis. This article briefly summarizes CDI incidence, management and preventive strategies. The authors intend to raise awareness of this disease among Chinese physicians and health workers, in order to minimize the medical and economic burden of a potential epidemic in the future.

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly. Study registration ISRCTN65924234

Background: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it. Methods: We studied 36 young Hispanic adults without diabetes (ages 18–40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups. Results: Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese. Conclusions: Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.

Background: Magnesium is associated with lower risk of sudden cardiac death, possibly through antiarrhythmic mechanisms. Magnesium influences endothelial function, inflammation, blood pressure, and diabetes, but a direct relation with coronary heart disease (CHD) risk has not been established. Methods and Results: We prospectively examined the association between dietary and plasma magnesium and risk of CHD among women in the Nurses' Health Study. The association for magnesium intake was examined among 86 323 women free of disease in 1980. Information on magnesium intake and lifestyle factors was ascertained every 2 to 4 years through questionnaires. Through 2008, 3614 cases of CHD (2511 nonfatal/1103 fatal) were documented. For plasma magnesium, we conducted a nested case–control analysis, with 458 cases of incident CHD (400 nonfatal/58 fatal) matched to controls (1:1) on age, smoking, fasting status, and date of blood sampling. Higher magnesium intake was not associated with lower risk of total CHD (P‐linear trend=0.12) or nonfatal CHD (P‐linear trend=0.88) in multivariable models. However, magnesium intake was inversely associated with risk of fatal CHD. The RR comparing quintile 5 to quintile 1 of magnesium intake was 0.61 (95% CI, 0.45 to 0.84; P‐linear trend=0.003). The association between magnesium intake and risk of fatal CHD appeared to be mediated partially by hypertension. Plasma magnesium levels above 2.0 mg/dL were associated with lower risk of CHD, although not independent of other cardiovascular biomarkers (RR, 0.67; 95% CI, 0.44 to 1.04). Conclusions: Dietary and plasma magnesium were not associated with total CHD incidence in this population of women. Dietary magnesium intake was inversely associated with fatal CHD, which may be mediated in part by hypertension.

Background: Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results: TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions: Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing.

Background: Recent work has demonstrated that fall risk can be attributed to cognitive as well as motor deficits. Indeed, everyday walking in complex environments utilizes executive function, dual tasking, planning and scanning, all while walking forward. Pilot studies suggest that a multi-modal intervention that combines treadmill training to target motor function and a virtual reality obstacle course to address the cognitive components of fall risk may be used to successfully address the motor-cognitive interactions that are fundamental for fall risk reduction. The proposed randomized controlled trial will evaluate the effects of treadmill training augmented with virtual reality on fall risk. Methods/Design: Three hundred older adults with a history of falls will be recruited to participate in this study. This will include older adults (n=100), patients with mild cognitive impairment (n=100), and patients with Parkinson’s disease (n=100). These three sub-groups will be recruited in order to evaluate the effects of the intervention in people with a range of motor and cognitive deficits. Subjects will be randomly assigned to the intervention group (treadmill training with virtual reality) or to the active-control group (treadmill training without virtual reality). Each person will participate in a training program set in an outpatient setting 3 times per week for 6 weeks. Assessments will take place before, after, and 1 month and 6 months after the completion of the training. A falls calendar will be kept by each participant for 6 months after completing the training to assess fall incidence (i.e., the number of falls, multiple falls and falls rate). In addition, we will measure gait under usual and dual task conditions, balance, community mobility, health related quality of life, user satisfaction and cognitive function. Discussion: This randomized controlled trial will demonstrate the extent to which an intervention that combines treadmill training augmented by virtual reality reduces fall risk, improves mobility and enhances cognitive function in a diverse group of older adults. In addition, the comparison to an active control group that undergoes treadmill training without virtual reality will provide evidence as to the added value of addressing motor cognitive interactions as an integrated unit.

Background: The societal burden of eating disorders is clear, and though there is a compelling need for a public health approach to eating disorders prevention, public health professionals have yet to take up the challenge. Discussion: The article lays out an argument for what steps need to be taken to bring a public health approach to eating disorders prevention. First, stock is taken of what the field has achieved so far, using tools from the prevention science literature, and, second, a research plan of action is offered that plays to the unique strengths of public health, drawing on a triggers-to-action framework from public health law. Minimal participation was found from public health professionals in eating disorders prevention research, and the vast majority of prevention research to date was found to be concentrated within the disciplines of psychology and psychiatry. Extreme disciplinary concentration of the research has led to a preponderance of individually targeted prevention strategies with little research focused on environmental targets, particularly at the macro level. New environmental initiatives are now emerging, such as a government-sponsored mass media anti-dieting campaign, and legal bans on extremely thin models in advertising, but for the most part, they have yet to be evaluated. A triggers-to-action framework, which focuses on evidentiary base, practical considerations, and political will, developed in public health law provides a basis for a strategic research plan for a public health approach to eating disorders prevention. Summary: There is enormous potential for growth in the scope and diversity of eating disorder prevention research strategies, particularly those targeting the macro environment. A public health approach will require a strategic plan for research that leverages the macro environment for prevention. The full engagement of public health professionals will bring to the field the much broader range of preventive strategies and perspectives needed to tackle the problem of eating disorders.

The Hospital Elder Life Program (HELP), an effective intervention to prevent delirium in older hospitalized adults, has been successfully replicated in a community teaching hospital as a quality improvement project. This article reports on successfully sustaining the program over 7 years and expanding its scale from one to six inpatient units at the same hospital. The program currently serves more than 7,000 older patients annually and is accepted as the standard of care throughout the hospital. Innovations that enhanced scalability and widespread implementation included ensuring dedicated staffing for the program, local adaptations to streamline protocols, continuous recruitment of volunteers, and more-efficient data collection. Outcomes include a lower rate of incident delirium; shorter length of stay (LOS); greater satisfaction of patients, families, and nursing staff; and significantly lower costs for the hospital. The financial return of the program, estimated at more than $7.3 million per year during 2008, comprises cost savings from delirium prevention and revenue generated from freeing up hospital beds (shorter LOS of HELP patients with and without delirium). Delirium poses a major challenge for hospital quality of care, patient safety, Medicare no-pay conditions, and costs of hospital care for older persons. Faced with rising numbers of elderly patients, hospitals can use HELP to improve the quality and cost-effectiveness of care.

Background: Nutrition and lifestyle are well-defined modulators of chronic diseases. Poor dietary habits (such as high intake of processed foods rich in fat and low intake of fruits and vegetables), as well as a sedentary lifestyle clearly contribute to today’s compromised quality of life in the United States. It is becoming increasingly clear that nutrition can modulate the toxicity of environmental pollutants. Objectives: Our goal in this commentary is to discuss the recommendation that nutrition should be considered a necessary variable in the study of human disease associated with exposure to environmental pollutants. Discussion: Certain diets can contribute to compromised health by being a source of exposure to environmental toxic pollutants. Many of these pollutants are fat soluble, and thus fatty foods often contain higher levels of persistent organics than does vegetable matter. Nutrition can dictate the lipid milieu, oxidative stress, and antioxidant status within cells. The modulation of these parameters by an individual’s nutritional status may have profound affects on biological processes, and in turn influence the effects of environmental pollutants to cause disease or dysfunction. For example, potential adverse health effects associated with exposure to polychlorinated biphenyls may increase as a result of ingestion of certain dietary fats, whereas ingestion of fruits and vegetables, rich in antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide protection. Conclusions: We recommend that future directions in environmental health research explore this nutritional paradigm that incorporates a consideration of the relationships between nutrition and lifestyle, exposure to environmental toxicants, and disease. Nutritional interventions may provide the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults.

While the association of a number of risk factors, such as family history and reproductive patterns, with breast cancer has been well established for many years, work in the past 10–15 years also has added substantially to our understanding of disease etiology. Contributions of particular note include the delineation of the role of endogenous and exogenous estrogens to breast cancer risk, and the discovery and quantification of risk associated with several gene mutations (e.g. BRCA1). Although it is difficult to integrate all epidemiologic data into a single biologic model, it is clear that several important components or pathways exist. Early life events probably determine both the number of susceptible breast cells at risk and whether mutations occur in these cells. High endogenous estrogens are well established as an important cause of breast cancer, and many known risk factors appear to operate through this pathway. Estrogens (and probably other growth factors) appear to accelerate the development of breast cancer at many points along the progression from early mutation to tumor metastasis, and appear to be influential at many points in a woman's life. These data now provide a basis for a number of strategies that can reduce risk of breast cancer, although some strategies represent complex decision-making. Together, the modification of nutritional and lifestyle risk factors and the judicious use of chemopreventive agents could have a major impact on breast cancer incidence. Further research is needed in many areas, but a few specific arenas are given particular mention.