186 research outputs found

    A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial)

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    Aims AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. Methods: Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. Results: Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months—treatment effect vs. Control: +1.24 mL/kg/min (95% confidence interval 0.26–2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). Conclusion: Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. Trial Registration Number NCT01311791

    Pan-Britain, mixed-methods study of multidisciplinary teams teaching parents to manage children's long-term kidney conditions at home: Study protocol

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    Background Care of children and young people (children) with long-term kidney conditions is usually managed by multidisciplinary teams. Published guidance recommends that whenever possible children with long-term conditions remain at home, meaning parents may be responsible for performing the majority of clinical care-giving. Multidisciplinary team members, therefore, spend considerable time promoting parents' learning about care-delivery and monitoring care-giving. However, this parent-educative aspect of clinicians' role is rarely articulated in the literature so little evidence exists to inform professionals' parent-teaching interventions. Methods This ongoing study addresses this issue using a combination of quantitative and qualitative methods involving the twelve children's kidney units in England, Scotland and Wales. Phase I involves a survey of multidisciplinary team members' parent-teaching interventions using: i) A telephone-administered questionnaire to determine: the numbers of professionals from different disciplines in each team, the information/skills individual professionals relay to parents and the teaching strategies/interventions they use. Data will be managed using SPSS to produce descriptive statistics ii) Digitally-recorded, qualitative group or individual interviews with multidisciplinary team members to explore their accounts of the parent-teaching component of their role. Interviews will be transcribed anonymously and analysed using Framework Technique. Sampling criteria will be derived from analysis to identify one/two unit(s) for subsequent in-depth study Phase II involves six prospective, ethnographic case-studies of professional-parent interactions during parent-teaching encounters. Parents of six children with a long-term kidney condition will be purposively sampled according to their child's age, diagnosis, ethnicity and the clinical care-giving required; snowball sampling will identify the professionals involved in each case-study. Participants will provide signed consent; data gathering will involve a combination of: minimally-obtrusive observations in the clinical setting and families' homes; de-briefing interviews with participants to obtain views on selected interactions; focussed 'verbatim' field-notes, and case-note reviews. Data gathering will focus on communication between parents and professionals as parents learn care-giving skills and knowledge. Interviews will be digitally recorded and transcribed anonymously. Discussion This study involves an iterative-inductive approach and will provide a unique, detailed insight into the social context in which professionals teach and parents learn; it will inform professionals' parent-educative roles, educational curricula, and health care polic

    Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

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    Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

    Rapid and Simple Method for the Most-Probable-Number Estimation of Arsenic-Reducing Bacteria

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    A rapid and simple most-probable-number (MPN) procedure for the enumeration of dissimilatory arsenic-reducing bacteria (DARB) is presented. The method is based on the specific detection of arsenite, the end product of anaerobic arsenate respiration, by a precipitation reaction with sulfide. After 4 weeks of incubation, the medium for the MPN method is acidified to pH 6 and sulfide is added to a final concentration of about 1 mM. The brightly yellow arsenic trisulfide precipitates immediately and can easily be scored at arsenite concentrations as low as 0.05 mM. Abiotic reduction of arsenate upon sulfide addition, which could yield false positives, apparently produces a soluble As-S intermediate, which does not precipitate until about 1 h after sulfide addition. Using the new MPN method, population estimates of pure cultures of DARB were similar to direct cell counts. MPNs of environmental water and sediment samples yielded DARB numbers between 10(1) and 10(5) cells per ml or gram (dry weight), respectively. Poisoned and sterilized controls showed that potential abiotic reductants in environmental samples did not interfere with the MPN estimates. A major advantage is that the assay can be easily scaled to a microtiter plate format, enabling analysis of large numbers of samples by use of multichannel pipettors. Overall, the MPN method provides a rapid and simple means for estimating population sizes of DARB, a diverse group of organisms for which no comprehensive molecular markers have been developed yet
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