Clinical Prognosis of Right-Sided Infective Endocarditis not Associated with Cardiac Devices or Intravenous Drug use : a Cohort Study and Meta-Analysis

Right-sided infective endocarditis (RSIE), classically associated with intravenous drug use or intracardiac devices, is considered a good-prognosis infective endocarditis (IE) form. However, predisposing factors and prognosis for "NODID" RSIE (NOt associated with cardiac Devices or Intravenous Drug use) remain unclear. The aim of this study was to evaluate predisposing factors and prognosis of NODID RSIE compared to other RSIE forms. A retrospective cohort study (January 2008-January 2019) was conducted in a reference center on 300 patients diagnosed with IE. Endocarditis-related events were defined as related to IE in mortality or open-heart surgery during follow-up. A review and meta-analysis of associated literature (January 2008-January 2019) were also performed. Fifty-seven patients presented RSIE (19%), 22 of which were NODID RSIE (39%). Use of intravascular catheters (23% vs 3%; p = 0.027) and congenital heart diseases (18% vs 0%; p = 0.019) were associated with NODID RSIE. This group had a higher in-hospital mortality (23% vs 3%; p = 0.027) and endocarditis-related event rates (41% vs 6%; p = 0.001) than non-NODID RSIE. Furthermore, NODID RSIE was independently associated with in-hospital endocarditis-related events (OR = 19.29; 95%CI:2.23-167.16; p = 0.007). Our meta-analysis evaluated four studies and identified 96 cases (30%) of NODID RSIE from 320 total RSIE cases. NODID RSIE patients demonstrated higher in-hospital mortality (RR = 2.81; 95%CI:1.61-4.90; p < 0.001; I = 0.0%) and necessity of open-heart surgery (RR = 13.89; 95%CI:4.14-46.60; p < 0.001; I = 0.0%) than non-NODID RSIE cases. Our study suggests that NODID RSIE has the highest endocarditis-related event rate and in-hospital mortality among RSIE cases and therefore should not be considered a good-prognosis IE

Cost-effectiveness of exercise referral schemes enhanced by self-management strategies to battle sedentary behaviour in older adults: Protocol for an economic evaluation alongside the SITLESS three-armed pragmatic randomised controlled trial

Introduction: Promoting physical activity (PA) and reducing sedentary behaviour (SB) may exert beneficial effects on the older adult population, improving behavioural, functional, health and psychosocial outcomes in addition to reducing health, social care and personal costs. This paper describes the planned economic evaluation of SITLESS, a multicountry three-armed pragmatic randomised controlled trial (RCT) which aims to assess the short-term and long-term effectiveness and cost-effectiveness of a complex intervention on SB and PA in community-dwelling older adults, based on exercise referral schemes enhanced by a group intervention providing self-management strategies to encourage lifestyle change. Methods and analysis: A within-trial economic evaluation and long-term model from both a National Health Service/personal social services perspective and a broader societal perspective will be undertaken alongside the SITLESS multinational RCT. Healthcare costs (hospitalisations, accident and emergency visits, appointment with health professionals) and social care costs (eg, community care) will be included in the economic evaluation. For the cost-utility analysis, quality-adjusted life-years will be measured using the EQ-5D-5L and capability well-being measured using the ICEpop CAPability measure for Older people (ICECAP-O) questionnaire. Other effectiveness outcomes (health related, behavioural, functional) will be incorporated into a cost-effectiveness analysis and cost-consequence analysis. The multinational nature of this RCT implies a hierarchical structure of the data and unobserved heterogeneity between clusters that needs to be adequately modelled with appropriate statistical and econometric techniques. In addition, a long-term population health economic model will be developed and will synthesise and extrapolate within-trial data with additional data extracted from the literature linking PA and SB outcomes with longer term health states. Methods guidance for population health economic evaluation will be adopted including the use of a long-time horizon, 1.5% discount rate for costs and benefits, cost consequence analysis framework and a multisector perspective. Ethics and dissemination: The study design was approved by the ethics and research committee of each intervention site: the Ethics and Research Committee of Ramon Llull University (reference number: 1314001P) (Fundació Blanquerna, Spain), the Regional Committees on Health Research Ethics for Southern Denmark (reference number: S-20150186) (University of Southern Denmark, Denmark), Office for Research Ethics Committees in Northern Ireland (ORECNI reference number: 16/NI/0185) (Queen’s University of Belfast) and the Ethical Review Board of Ulm University (reference number: 354/15) (Ulm, Germany). Participation is voluntary and all participants will be asked to sign informed consent before the start of the study. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 634 270. This article reflects only the authors' view and the Commission is not responsible for any use that may be made of the information it contains. The findings of the study will be disseminated to different target groups (academia, policymakers, end users) through different means following the national ethical guidelines and the dissemination regulation of the Horizon 2020 funding agency. Use of the EuroQol was registered with the EuroQol Group in 2016. Use of the ICECAP-O was registered with the University of Birmingham in March 2017. Trial registration number: NCT02629666; Pre-results

Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus

Background: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether diet, physical activity or both can prevent or delay T2DM and its associated complications in at-risk people is unknown. Objectives: To assess the effects of diet, physical activity or both on the prevention or delay of T2DM and its associated complications in people at increased risk of developing T2DM. Search methods: This is an update of the Cochrane Review published in 2008. We searched the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was January 2017. We continuously used a MEDLINE email alert service to identify newly published studies using the same search strategy as described for MEDLINE up to September 2017. Selection criteria: We included randomised controlled trials (RCTs) with a duration of two years or more. Data collection and analysis: We used standard Cochrane methodology for data collection and analysis. We assessed the overall quality of the evidence using GRADE. Main results: We included 12 RCTs randomising 5238 people. One trial contributed 41% of all participants. The duration of the interventions varied from two to six years. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains. Eleven trials compared diet plus physical activity with standard or no treatment. Nine RCTs included participants with impaired glucose tolerance (IGT), one RCT included participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of 12 deaths occurred in 2049 participants in the diet plus physical activity groups compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI 0.50 to 2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials; very low-quality evidence). The definition of T2DM incidence varied among the included trials. Altogether 315 of 2122 diet plus physical activity participants (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%) (RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511 participants, 11 trials; moderate-quality evidence). Two trials reported serious adverse events. In one trial no adverse events occurred. In the other trial one of 51 diet plus physical activity participants compared with none of 51 comparator participants experienced a serious adverse event (low-quality evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus physical activity participants and four of 1637 comparator participants (the RR ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low-quality evidence). Only one trial reported that no non-fatal myocardial infarction or non-fatal stroke had occurred (low-quality evidence). Two trials reported that none of the participants had experienced hypoglycaemia. One trial investigated health-related quality of life in 2144 participants and noted that a minimal important difference between intervention groups was not reached (very low-quality evidence). Three trials evaluated costs of the interventions in 2755 participants. The largest trial of these reported an analysis of costs from the health system perspective and society perspective reflecting USD 31,500 and USD 51,600 per quality-adjusted life year (QALY) with diet plus physical activity, respectively (low-quality evidence). There were no data on blindness or end-stage renal disease. One trial compared a diet-only intervention with a physical-activity intervention or standard treatment. The participants had IGT. Three of 130 participants in the diet group compared with none of the 141 participants in the physical activity group died (very low-quality evidence). None of the participants died because of cardiovascular disease (very low-quality evidence). Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical activity participants (41.1%) group developed T2DM (very low-quality evidence). No adverse events were recorded (very low-quality evidence). There were no data on non-fatal myocardial infarction, non-fatal stroke, blindness, end-stage renal disease, health-related quality of life or socioeconomic effects. Two trials compared physical activity with standard treatment in 397 participants. One trial included participants with IGT, the other trial included participants with IGT, IFG or both. One trial reported that none of the 141 physical activity participants compared with three of 133 control participants died. The other trial reported that three of 84 physical activity participants and one of 39 control participants died (very low-quality evidence). In one trial T2DM developed in 58 of 141 physical activity participants (41.1%) compared with 90 of 133 control participants (67.7%). In the other trial 10 of 84 physical activity participants (11.9%) compared with seven of 39 control participants (18%) developed T2DM (very low-quality evidence). Serious adverse events were rarely reported (one trial noted no events, one trial described events in three of 66 physical activity participants compared with one of 39 control participants - very low-quality evidence). Only one trial reported on cardiovascular mortality (none of 274 participants died - very low-quality evidence). Non-fatal myocardial infarction or stroke were rarely observed in the one trial randomising 123 participants (very low-quality evidence). One trial reported that none of the participants in the trial experienced hypoglycaemia. One trial investigating health-related quality of life in 123 participants showed no substantial differences between intervention groups (very low-quality evidence). There were no data on blindness or socioeconomic effects. Authors' conclusions: There is no firm evidence that diet alone or physical activity alone compared to standard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM. However, diet plus physical activity reduces or delays the incidence of T2DM in people with IGT. Data are lacking for the effect of diet plus physical activity for people with intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did not investigate patient-important outcomes

Respiratory syncytial virus: diagnosis, prevention and management.

Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom. RSV has been shown to account for 22% of all episodes of acute lower respiratory tract infection in children globally. RSV hospitalization, that is, RSV severe disease, has also been associated with subsequent chronic respiratory morbidity. Routine viral testing in all children is not currently recommended by the United Kingdom National Institute for Health and Care Excellence (NICE) or the American Academy of Pediatrics (AAP) guidance and management is largely supportive. There is some evidence for the use of ribavirin in severely immunocompromised children. Emphasis is placed on prevention of RSV infection through infection control measures both in hospital and in the community, and the use of the RSV-specific monoclonal antibody, palivizumab, for certain high-risk groups of infants. New RSV antivirals and vaccines are currently in development. Ongoing work is needed to improve the prevention of RSV infection, not only because of the acute morbidity and mortality, but also to reduce the associated chronic respiratory morbidity after severe infection

Withdrawal of infliximab therapy in ankylosing spondylitis in persistent clinical remission, results from the REMINEA study

Altres ajuts: This work is conducted under the umbrella of the Rheumatology Society of Catalonia and supported by Merck Research Laboratories.Background: Recent data suggest that anti-TNF doses can be reduced in ankylosing spondylitis (AS) patients. Some authors even propose withdrawing treatment in patients in clinical remission; however, at present there is no evidence to support this. Objective: To assess how long AS patients with persistent clinical remission remained free of flares after anti-TNF withdrawal and to evaluate the effects of treatment reintroduction. We also analyze the characteristics of patients who did not present clinical relapse. Methods: Multicenter, prospective, observational study of a cohort of patients with active AS who had received infliximab as a first anti-TNF treatment and who presented persistent remission (more than 6 months). We recorded at baseline and every 6-8 weeks over the 12-month period the age, gender, disease duration, peripheral arthritis or enthesitis, HLA-B27 status, BASDAI, CRP, ESR, BASFI, and three visual analogue scales, spine global pain, spinal night time pain, and patient's global assessment. Results: Thirty-six out of 107 patients (34%) presented persistent remission and were included in our study. After treatment withdrawal, 21 of these 36 patients (58%) presented clinical relapse during follow-up. Infliximab therapy was reintroduced and only 52% achieved clinical remission, as they had before the discontinuation of infliximab; in an additional 10%, reintroduction of infliximab was ineffective, obliging us to change the anti-TNF therapy. No clinical or biological factors were associated with the occurrence of relapse during the follow-up. Conclusions: Two thirds of patients in clinical remission presented clinical relapse shortly after infliximab withdrawal. Although the reintroduction of infliximab treatment was safe, half of the patients did not present the same clinical response that they had achieved prior to treatment withdrawal

Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old (Review)

Q1Q1CD004873BACKGROUND: This is an update of the original Cochrane review published in 2005 and updated in 2007. Acute bronchiolitis is the leading cause of medical emergencies during winter in children younger than two years of age. Chest physiotherapy is thought to assist infants in the clearance of secretions and to decrease ventilatory effort. OBJECTIVES: The main objective was to determine the efficacy of chest physiotherapy in infants aged less than 24 months old with acute bronchiolitis. A secondary objective was to determine the efficacy of different techniques of chest physiotherapy (for example, vibration and percussion and passive forced exhalation). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to November week 3, 2011), MEDLINE in-process and other non-indexed citations (8 December 2011), EMBASE.com (1990 to December 2011), CINAHL (1982 to December 2011), LILACS (1985 to December 2011) and Web of Science (1985 to December 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) in which chest physiotherapy was compared against no intervention or against another type of physiotherapy in bronchiolitis patients younger than 24 months of age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. Primary outcomes were respiratory parameters and improvement in severity of disease. Secondary outcomes were length of hospital stay, duration of oxygen supplementation and the use of bronchodilators and steroids. No pooling of data was possible. MAIN RESULTS: Nine clinical trials including 891 participants were included comparing physiotherapy with no intervention. Five trials (246 participants) evaluated vibration and percussion techniques and four trials (645 participants) evaluated passive expiratory techniques. We observed no significant differences in the severity of disease (eight trials, 867 participants). Results were negative for both types of physiotherapy. We observed no differences between groups in respiratory parameters (two trials, 118 participants), oxygen requirements (one trial, 50 participants), length of stay (five trials, 222 participants) or severe side effects (two trials, 595 participants). Differences in mild transient adverse effects (vomiting and respiratory instability) have been observed (one trial, 496 participants). AUTHORS' CONCLUSIONS: Since the last publication of this review new good-quality evidence has appeared, strengthening the conclusions of the review. Chest physiotherapy does not improve the severity of the disease, respiratory parameters, or reduce length of hospital stay or oxygen requirements in hospitalised infants with acute bronchiolitis not on mechanical ventilation. Chest physiotherapy modalities (vibration and percussion or forced expiratory techniques) have shown equally negative results

Empirical evidence about inconsistency among studies in a pair-wise meta-analysis

This paper investigates how inconsistency (as measured by the I(2) statistic) among studies in a meta‐analysis may differ, according to the type of outcome data and effect measure. We used hierarchical models to analyse data from 3873 binary, 5132 continuous and 880 mixed outcome meta‐analyses within the Cochrane Database of Systematic Reviews. Predictive distributions for inconsistency expected in future meta‐analyses were obtained, which can inform priors for between‐study variance. Inconsistency estimates were highest on average for binary outcome meta‐analyses of risk differences and continuous outcome meta‐analyses. For a planned binary outcome meta‐analysis in a general research setting, the predictive distribution for inconsistency among log odds ratios had median 22% and 95% CI: 12% to 39%. For a continuous outcome meta‐analysis, the predictive distribution for inconsistency among standardized mean differences had median 40% and 95% CI: 15% to 73%. Levels of inconsistency were similar for binary data measured by log odds ratios and log relative risks. Fitted distributions for inconsistency expected in continuous outcome meta‐analyses using mean differences were almost identical to those using standardized mean differences. The empirical evidence on inconsistency gives guidance on which outcome measures are most likely to be consistent in particular circumstances and facilitates Bayesian meta‐analysis with an informative prior for heterogeneity. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd