Human Rabies - Virginia, 2017.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected.

Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD Bone Study.

Context: In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown.

Objective: The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men.

Design: This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study.

Long-term outcomes of bariatric surgery: a National Institutes of Health symposium.

Importance: The clinical evidence base demonstrating bariatric surgery's health benefits is much larger than it was when the National Institutes of Health last held a consensus panel in 1991. Still, it remains unclear whether ongoing studies will address critical questions about long-term complication rates and the sustainability of weight loss and comorbidity control.

Objective: To summarize findings from a multidisciplinary workshop convened in May 2013 by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial.

Importance: In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.

Objective: To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.

Understanding the context of health for persons with multiple chronic conditions: moving from what is the matter to what matters.

Purpose: An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC).

Methods: Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research.

Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial.

Importance: Dietary supplements have been proposed as a mechanism to improve health and prevent disease.

Objective: To determine if supplementing diet with long-chain ω-3 polyunsaturated fatty acids or with macular xanthophylls results in a reduced rate of cardiovascular disease (CVD).

Design, Setting, And Participants: The Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4203 participants recruited from 82 US academic and community ophthalmology clinics, who were followed up for a median of 4.

Ankle brachial index values, leg symptoms, and functional performance among community-dwelling older men and women in the lifestyle interventions and independence for elders study.

Background: The prevalence and significance of low normal and abnormal ankle brachial index (ABI) values in a community-dwelling population of sedentary, older individuals is unknown. We describe the prevalence of categories of definite peripheral artery disease (PAD), borderline ABI, low normal ABI, and no PAD and their association with lower-extremity functional performance in the LIFE Study population.

Methods And Results: Participants age 70 to 89 in the LIFE Study underwent baseline measurement of the ABI, 400-m walk, and 4-m walking velocity.

Childhood Obesity Prevention and Treatment Research (COPTR): interventions addressing multiple influences in childhood and adolescent obesity.

This paper is the first of five papers in this issue that describes a new research consortium funded by the National Institutes of Health. It describes the design characteristics of the Childhood Obesity Prevention and Treatment Research (COPTR) trials and common measurements across the trials. The COPTR Consortium is conducting interventions to prevent obesity in pre-schoolers and treat overweight or obese 7-13 year olds.

Centers for cardiovascular outcomes research: defining a collaborative vision.

Background: Recognizing the value of outcomes research to understand and bridge translational gaps, to establish evidence in clinical practice and delivery of medicine, and to generate new hypotheses on ongoing questions of treatment and care, the National Heart, Lung, and Blood Institute of the National Institutes of Health established the Centers for Cardiovascular Outcomes Research program in 2010.

Methods And Results: The National Heart, Lung, and Blood Institute funded 3 centers and a research coordinating unit. Each center has an independent project focus, including (1) characterizing care transition and predicting clinical events and quality of life for patients discharged after an acute coronary syndrome; (2) identifying center and regional factors associated with better patient outcomes across several cardiovascular conditions and procedures; and (3) examining the impact of healthcare reform in Massachusetts on overall and disparate care and outcomes for several cardiovascular conditions and venous thromboembolism.

Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial.

Objective: Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial.

Research Design And Methods: ACCORD participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.

Severe hypoglycemia symptoms, antecedent behaviors, immediate consequences and association with glycemia medication usage: Secondary analysis of the ACCORD clinical trial data.

Background: Hypoglycemia is a common complication of diabetes treatment. This paper describes symptoms, predecessors, consequences and medications associated with the first episode of severe hypoglycemia among ACCORD participants with type 2 diabetes, and compares these between intensive (Int: goal A1C <6.0%) and standard (Std, goal A1C 7-7.

Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants.

Objective: To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy.

Research Design And Methods: An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥ 20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤ 2% increase); and placebo control subjects (n = 565).

The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study.

Objective: The aim of this study was to examine the relationship between frequent and unrecognized hypoglycemia and mortality in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study cohort.

Research Design And Methods: A total of 10,096 ACCORD study participants with follow-up for both hypoglycemia and mortality were included. Hazard ratios (95% CIs) relating the risk of death to the updated annualized number of hypoglycemic episodes and the updated annualized number of intervals with unrecognized hypoglycemia were obtained using Cox proportional hazards regression models, allowing for these hypoglycemia variables as time-dependent covariates and controlling for the baseline covariates.

The Lifestyle Interventions and Independence for Elders Study: design and methods.

Background: As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking.

Estrogen receptor polymorphisms and the vascular effects of hormone therapy.

Objective: To test whether estrogen receptor polymorphisms modify the effects of postmenopausal hormone therapy on biomarkers and on risk of coronary heart disease events, stroke, or venous thromboembolism.

Methods And Results: The design was a nested case-control study in the Women's Health Initiative trials of postmenopausal hormone therapy. The study included all cases in the first 4 years: 359 cases of coronary heart disease, 248 of stroke, and 217 of venous thromboembolism.

Lack of association between thiazolidinediones and macular edema in type 2 diabetes: the ACCORD eye substudy.

Objective: To assess the cross-sectional association of thiazolidinediones with diabetic macular edema (DME).

Methods: The cross-sectional association of DME and visual acuity with thiazolidinediones was examined by means of baseline fundus photographs and visual acuity measurements from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Visual acuity was assessed in 9690 participants in the ACCORD trial, and 3473 of these participants had fundus photographs that were centrally read in a standardized fashion by masked graders to assess DME and retinopathy from October 23, 2003, to March 10, 2006.

Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Objective: To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality.

Research Design And Methods: Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics.

Results: There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.

The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study.

Objectives: To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A(1C)) achieved during therapy.

Design: Post hoc epidemiological analysis of a double 2x2 factorial, randomised, controlled trial.

Setting: Diabetes clinics, research clinics, and primary care clinics.

The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study.

Objective: To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Design: Retrospective epidemiological analysis of data from the ACCORD trial. Setting Diabetes clinics, research clinics, and primary care clinics.

Appropriateness of cholesterol management in primary care by sex and level of cardiovascular risk.

A study was undertaken to ascertain the appropriateness of lipid screening and management per the Third Report of the Adult Treatment Panel National Cholesterol Education Program (ATP III) guideline in a sample of North Carolina primary care practices. Demographics, cholesterol values, and comorbid conditions were abstracted from the medical records from 60 community practices participating in a randomized practice-based trial (Guideline Adherence for Heart Health). Eligible patients were aged 21 to 84 years, seen during the baseline period of June 1, 2001, through May 31, 2003, and who were not taking lipid-lowering therapy.

Impact of a multifaceted intervention on cholesterol management in primary care practices: guideline adherence for heart health randomized trial.

Background: Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor.

Methods: We recruited 68 primary care family and internal medicine practices; 66 were randomly allocated to a study arm; 5 practices withdrew, resulting in 29 receiving the Third Adult Treatment Panel (ATP III) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7). The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III-recommended treatment.