Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark

Background Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. Methods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. Results The median age of the participants was 38 years, and 60% were women; 78% were white, and 22% black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. Conclusions In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443 .).

BackgroundSport drinks are ubiquitous within the recreational and competitive fitness and sporting world. Most are manufactured and artificially flavored carbohydrate-electrolyte beverages. Recently, attention has been given to coconut water, a natural alternative to manufactured sport drinks, with initial evidence indicating efficacy with regard to maintaining hydration. We compared coconut water and a carbohydrate-electrolyte sport drink on measures of hydration and physical performance in exercise-trained men.MethodsFollowing a 60-minute bout of dehydrating treadmill exercise, 12 exercise-trained men (26.6 ± 5.7 yrs) received bottled water (BW), pure coconut water (VitaCoco®: CW), coconut water from concentrate (CWC), or a carbohydrate-electrolyte sport drink (SD) [a fluid amount based on body mass loss during the dehydrating exercise] on four occasions (separated by at least 5 days) in a random order, single blind (subject and not investigators), cross-over design. Hydration status (body mass, fluid retention, plasma osmolality, urine specific gravity) and performance (treadmill time to exhaustion; assessed after rehydration) were determined during the recovery period. Subjective measures of thirst, bloatedness, refreshed, stomach upset, and tiredness were also determined using a 5-point visual analog scale.ResultsSubjects lost approximately 1.7 kg (~2% of body mass) during the dehydrating exercise and regained this amount in a relatively similar manner following consumption of all conditions. No differences were noted between coconut water (CW or CWC) and SD for any measures of fluid retention (p > 0.05). Regarding exercise performance, no significant difference (p > 0.05) was noted between BW (11.9 ± 5.9 min), CW (12.3 ± 5.8 min), CWC (11.9 ± 6.0 min), and SD (12.8 ± 4.9 min). In general, subjects reported feeling more bloated and experienced greater stomach upset with the CW and CWC conditions.ConclusionAll tested beverages are capable of promoting rehydration and supporting subsequent exercise. Little difference is noted between the four tested conditions with regard to markers of hydration or exercise performance in a sample of young, healthy men. Additional study inclusive of a more demanding dehydration protocol, as well as a time trial test as the measure of exercise performance, may more specifically determine the efficacy of these beverages on enhancing hydration and performance following dehydrating exercise.

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BackgroundThis randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms.MethodsSixty-one adults were enrolled (age 36.5 ± 12.6 years; height 165.1 ± 9.2 cm; weight 75.4 ± 17.3 kg) and randomized to either Digestive Advantage™ Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use.ResultsMeasured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables.ConclusionIn conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses.Trial RegistrationClinicalTrials.gov Identifier: NCT00881322

The safety and immunogenicity results from this study support inclusion of the GLA-SE adjuvant in this RSV vaccine for older adults and also support assessment of the efficacy of the vaccine in a larger clinical trial. Clinicaltrials.gov NCT02115815.

Although the association of obesity and hypertension is well recognized, the mechanisms involved in the pathogenesis of increased blood pressure in the obese are poorly understood. Recent studies addressing the impact of 1) body fat distribution on blood pressure and 2) dietary intake on sympathetic nervous system (SNS) activity suggest a plausible hypothesis that relates the hypertension of the obese to hyperinsulinemia and SNS stimulation. Hypertension in the obese is associated with fat accumulation in the upper body segments; this type of obesity is also characterized by hyperinsulinemia and insulin resistance. Insulin, moreover, is an important signal in the relationship between dietary intake and SNS activity: increased insulin levels are associated with SNS stimulation. The hyperinsulinemia of obesity may, therefore, increase blood pressure by 1) direct effects of insulin to stimulate renal sodium reabsorption, and 2) sympathetic stimulation of the heart, blood vessels, and kidney. Conversely, SNS suppression and diminished insulin following caloric restriction may explain the hypotensive effects of caloric restriction in obese hypertensive subjects. The hypothesis presented here emphasizes the important role of diet in the treatment of obese hypertensive subjects. The efficacy of caloric restriction, weight loss, and exercise in reducing blood pressure in the obese is linked to diminished insulin and SNS activity and may be viewed as evidence in favor of this hypothesis.

BACKGROUND: Dexmedetomidine is a potentially useful sedative for hospitalized children, but there is little published data regarding its safety, dosage, or efficacy. OBJECTIVE: To report our experience with dexmedetomidine for the sedation of hospitalized children. DESIGN: Retrospective case series. SETTING: Pediatric ICU of a university‐affiliated children's hospital. PATIENTS: We retrospectively examined data from the medical records of all children who received dexmedetomidine for sedation between December 2003 and October 2005. INTERVENTION: None. RESULTS: Dexmedetomidine was administered 74 times to 60 children (median age 1.5 years, range 0.1–17.2 years). The most common indications for ICU admission were respiratory distress/failure (53%), status–postcorrective cardiac surgery (19%), and other postoperative patients (18%). In 53% of cases dexmedetomidine was used to supplement ongoing sedation judged inadequatem and in 41% of cases it was used as a bridge to extubation while other sedatives were weaned or discontinued. Among all the children, the median dose to maintain adequate sedation was 0.7 μg/kg per hour (range 0.2–2.5 μg/kg per hour), with a median duration of therapy of 23 hours (range 3–451 hours). Most children (80%) experienced no adverse effects from the sedation, with hypotension (9%), hypertension (8%), and bradycardia (3%) the most common adverse events. For 93% of children who experienced a side effect, it resolved either without treatment or by withholding the infusion. CONCLUSIONS: In this cohort of children hospitalized in the ICU, dexmedetomidine appeared to be effective and to have few adverse effects. Dexmedetomidine may have a potentially useful role to play in sedating hospitalized children. Journal of Hospital Medicine 2008;3:142–147. © 2008 Society of Hospital Medicine.