Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF-TIMI 48 Trial.

BACKGROUND: The impact of different types of extracranial bleeding events on health-related quality of life and health-state utility among patients with atrial fibrillation is not well understood. METHODS AND RESULTS: The ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol-5D (EQ-5D-3L) questionnaire, prospectively collected at 3-month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health-state utility over 12 months following the event. Longitudinal mixed-effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (-0.029 [-0.044 to -0.014; P<0.001] and -0.029 [-0.046 to -0.012; P=0.001], respectively). These effects decreased in magnitude over time, and were no longer significant for major nongastrointestinal bleeds at 9 months, but remained borderline significant for major gastrointestinal bleeds at 12 months. Clinically relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility (-0.010 [-0.016 to -0.005] and -0.016 [-0.024 to -0.008]; P<0.001 for both), which remained relatively constant and statistically significant over the 12 months following the bleeding event. CONCLUSIONS: All categories of bleeding events were associated with negative impacts on health-state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391

Adapted motivational interviewing to improve the uptake of treatment for glaucoma in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Glaucoma is a chronic eye disease associated with irreversible visual loss. In Africa, glaucoma patients often present late, with very advanced disease. One-off procedures, such as laser or surgery, are recommended in Africa because of lack of or poor adherence to medical treatment. However, acceptance of surgery is usually extremely low. To prevent blindness, adherence to treatment needs to improve, using acceptable, replicable and cost-effective interventions. After reviewing the literature and interviewing patients in Bauchi (Nigeria) motivational interviewing (MI) was selected as the intervention for this trial, with adaptation for glaucoma (MIG). MI is designed to strengthen personal motivation for, and commitment to a specific goal by eliciting and exploring a person's reasons for change within an atmosphere of acceptance and compassion. The aim of this study is to assess whether MIG increases the uptake of laser or surgery amongst glaucoma patients where this is the recommended treatment. The hypothesis is that MIG increases the uptake of treatment. This will be the first trial of MI in Africa. METHODS: This is a hospital based, single centre, randomized controlled trial of MIG plus an information sheet on glaucoma and its treatment (the latter being "standard care") compared with standard care alone for glaucoma patients where the treatment recommended is surgery or laser.Those eligible for the trial are adults aged 17 years and above who live within 200 km of Bauchi with advanced glaucoma where the examining ophthalmologist recommends surgery or laser. After obtaining written informed consent, participants will be randomly allocated to MIG plus standard care, or standard care alone. Motivational interviewing will be delivered in Hausa or English by one of two MIG trained personnel. One hundred and fifty participants will be recruited to each arm. The primary outcome is the proportion of participants undergoing laser or surgery within two months of the date given to re attend for the procedure. MIG quality will be assessed using the validated MI treatment integrity scale. DISCUSSION: Motivational interviewing may be an important tool to increase the acceptance of treatment for glaucoma. The approach is potentially scalable and may be useful for other chronic conditions in Africa. TRIAL REGISTRATION: ISRCTN79330571 (Controlled-Trials.com)

Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke

'Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6-4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA

Authorship trends in software engineering

This paper aims to examine authorship trends in software engineering, especially those related to the number of authors, of scientific publications. We collected and mined around 70.000 entries from DBLP for 122 conferences and journals, for the period 1971–2012, in order to process several bibliometric indicators. We provide evidence that the number of authors of articles in software engineering is increasing on average around +0.40 authors/decade. The results also indicate that until 1980, the majority of the articles have a sole author, while nowadays articles with 3 or 4 authors represent almost half of the total.Fundação para a Ciência e a Tecnologia (FCT

Indications for and Utilization of ACE Inhibitors in Older Individuals with Diabetes

Angiotensin-converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) improve cardiovascular outcomes in high-risk individuals with diabetes. Despite the marked benefit, it is unknown what percentage of patients with diabetes would benefit from and what percentage actually receive this preventive therapy. OBJECTIVES : To examine the proportion of older diabetic patients with indications for ACE or ARB (ACE/ARB). To generate national estimates of ACE/ARB use. DESIGN AND PARTICIPANTS : Survey of 742 individuals≥55 years (representing 8.02 million U.S. adults) self-reporting diabetes in the 1999 to 2002 National Health and Nutrition Examination Survey. MEASUREMENTS : Prevalence of guideline indications (albuminuria, cardiovascular disease, hypertension) and other cardiac risk factors (hyperlipidemia, smoking) with potential benefit from ACE/ARB. Prevalence of ACE/ARB use overall and by clinical indication. RESULTS : Ninety-two percent had guideline indications for ACE/ARB. Including additional cardiac risk factors, the entire (100%) U.S. noninstitutionalized older population with diabetes had indications for ACE/ARB. Overall, 43% of the population received ACE/ARB. Hypertension was associated with higher rates of ACE/ARB use, while albuminuria and cardiovascular disease were not. As the number of indications increased, rates of use increased, however, the maximum prevalence of use was only 53% in individuals with 4 or more indications for ACE/ARB. CONCLUSIONS : ACE/ARB is indicated in virtually all older individuals with diabetes; yet, national rates of use are disturbingly low and key risk factors (albuminuria and cardiovascular disease) are being missed. To improve quality of diabetes care nationally, use of ACE/ARB therapy by ALL older diabetics may be a desirable addition to diabetes performance measurement sets.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74734/1/j.1525-1497.2006.00351.x.pd

Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: The Seniors Health and Activity Research Program Pilot (SHARP-P) Study, a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial.</p> <p>Methods</p> <p>SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment.</p> <p>Results</p> <p>Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome).</p> <p>Conclusions</p> <p>Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00688155">NCT00688155</a></p

Inflammatory mechanisms in ischemic stroke: therapeutic approaches

Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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