The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2 : a systematic review of cost-effectiveness studies

Tese de mestrado, Epidemiologia, Universidade de Lisboa, Faculdade de Medicina, 2015

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review.

BACKGROUND Extracorporeal membrane oxygenation (ECMO) offers therapeutic options in refractory respiratory and/or cardiac failure. Systemic anticoagulation with heparin is routinely administered. However, in patients with heparin-induced thrombocytopenia or heparin resistance, the direct thrombin inhibitor bivalirudin is a valid option and has been increasingly used for ECMO anticoagulation. We aimed at evaluating its safety and its optimal dosing for ECMO. METHODS Systematic web-based literature search of PubMed and EMBASE performed via National Health Service Library Evidence and manually, updated until January 30, 2016. RESULTS The search revealed 8 publications relevant to the topic (5 case reports). In total, 58 patients (24 pediatrics) were reported (18 received heparin as control groups). Bivalirudin was used with or without loading dose, followed by infusion at different ranges (lowest 0.1-0.2 mg/kg/h without loading dose; highest 0.5 mg/kg/h after loading dose). The strategies for monitoring anticoagulation and optimal targets were dissimilar (activated partial thromboplastin time 45-60 seconds to 42-88 seconds; activated clotting time 180-200 seconds to 200-220 seconds; thromboelastography in 1 study). CONCLUSION Bivalirudin loading dose was not always used; infusion range and anticoagulation targets were different. In this systematic review, we discuss the reasons for this variability. Larger studies are needed to establish the optimal approach with the use of bivalirudin for ECMO.

A Comparative Analysis of Two Slug Test Methods in Puget Lowland Glacio-Fluvial Sediments near Coupeville, WA

Two different slug test field methods are conducted in wells completed in a Puget Lowland aquifer and are examined for systematic error resulting from water column displacement techniques. Slug tests using the standard slug rod and the pneumatic method were repeated on the same wells and hydraulic conductivity estimates were calculated according to Bouwer & Rice and Hvorslev before using a non-parametric statistical test for analysis. Practical considerations of performing the tests in real life settings are also considered in the method comparison. Statistical analysis indicates that the slug rod method results in up to 90% larger hydraulic conductivity values than the pneumatic method, with at least a 95% certainty that the error is method related. This confirms the existence of a slug-rod bias in a real world scenario which has previously been demonstrated by others in synthetic aquifers. In addition to more accurate values, the pneumatic method requires less field labor, less decontamination, and provides the ability to control the magnitudes of the initial displacement, making it the superior slug test procedure.

Prolotherapy injections for chronic low back pain - A systematic review

Study Design. A systematic review of randomized and quasi-randomized controlled trials. Objectives. To determine the efficacy of prolotherapy injections in adults with chronic low back pain. Summary of Background Data. Prolotherapy is an injection-based treatment for chronic low back pain. Proponents of prolotherapy suggest that some back pain stems from weakened or damaged ligaments. Repeatedly injecting them with irritant solutions is thought to strengthen the ligaments and reduce pain and disability. Prolotherapy protocols usually include co-interventions to enhance the effectiveness of the injections. Methods. The authors searched MEDLINE, EMBASE, CINAHL, and Science Citation Index up to January 2004, and the Cochrane Controlled Trials Register 2004, issue 1, and consulted content experts. Both randomized and quasi-randomized controlled trials comparing prolotherapy injections to control injections, either alone or in combination with other treatments, were included. Studies had to include measures of pain and disability before and after the intervention. Two reviewers independently selected the trials and assessed them for methodologic quality. Treatment and control group protocols varied from study to study, making meta-analysis impossible. Results. Four studies, all of high quality and with a total of 344 participants, were included. All trials measured pain and disability levels at 6 months, three measured the proportion of participants reporting a greater than 50% reduction in pain or disability scores from baseline to 6 months. Two studies showed significant differences between the treatment and control groups for those reporting more than 50% reduction in pain or disability. Their results could not be pooled. In one, cointerventions confounded interpretation of results; in the other, there was no significant difference in mean pain and disability scores between the groups. In the third study, there was little or no difference between groups in the number of individuals who reported more than 50% improvement in pain and disability. The fourth study reporting only mean pain and disability scores showed no differences between groups. Conclusions. There is conflicting evidence regarding the efficacy of prolotherapy injections in reducing pain and disability in patients with chronic low back pain. Conclusions are confounded by clinical heterogeneity among studies and by the presence of co-interventions. There was no evidence that prolotherapy injections alone were more effective than control injections alone. However, in the presence of co-interventions, prolotherapy injections were more effective than control injections, more so when both injections and co-interventions were controlled concurrently.

Exercise training for patients with heart failure: A systematic review of factors that improve mortality and morbidity

PURPOSE: To determine the efficacy of exercise training and its effects on outcomes in patients with heart failure. METHODS: MEDLINE, Medscape, and the Cochrane Controlled Trials Registry were searched for trials of exercise training in heart failure patients. Data relating to training protocol, exercise capacity, and outcome measures were extracted and reviewed. RESULTS: A total of 81 studies were identified: 30 randomized controlled trials, five nonrandomized controlled trials, nine randomized crossover trials, and 37 longitudinal cohort studies. Exercise training was performed in 2387 patients. The average increment in peak oxygen consumption was 17% in 57 studies that measured oxygen consumption directly, 17% in 40 studies of aerobic training, 9% in three studies that only used strength training, 15% in 13 studies of combined aerobic and strength training, and 16% in the one study on inspiratory training. There were no reports of deaths that were directly related to exercise during more than 60,000 patient-hours of exercise training. During the training and follow-up periods of the randomized controlled trials, there were 56 combined (deaths or adverse events) events in the exercise groups and 75 combined events in the control groups (odds ratio [OR] = 0.98; 95% confidence interval [Cl]: 0.61 to 1.32; P = 0.60). During this same period, 26 exercising and 41 nonexercising subjects died (OR = 0.71; 95% CT: 0.37 to 1.02; P = 0.06). CONCLUSION: Exercise training is safe and effective in patients with heart failure. The risk of adverse events may be reduced, but further studies are required to determine whether there is any mortality benefit. (C) 2004 by Excerpta Medica Inc.

Community-based programmes to prevent pedestrian injuries in children 0-14 years: A systematic review

Community-based models for injury prevention have become an accepted part of the overall injury control strategy. This systematic review of the scientific literature examines the evidence for their effectiveness in reducing pedestrian injury in children 0-14 years of age. A comprehensive search of the literature was performed using the following study selection criteria: community-based intervention study; target population was children under 14 years; outcome measure is either pedestrian injury rates or observed child pedestrian or vehicle driver behaviour; and use of a community control or an historical control in the study design. Quality assessment and data abstraction was guided by a standardized procedure and performed independently by two authors. Data synthesis was in tabular and text form with meta-analysis not being possible due to the discrepancy in methods and measures between the studies.

Multidisciplinary strategies for the management of heart failure patients at high risk for admission - A systematic review of randomized trials

OBJECTIVES The aim of this study was to determine whether multidisciplinary strategies improve outcomes for heart failure (HF) patients. BACKGROUND Because the prognosis of HF remains poor despite pharmacotherapy, there is increasing interest in alternative models of care delivery for these patients. METHODS Randomized trials of multidisciplinary management programs in HF were identified by searching electronic databases and bibliographies and via contact with experts. RESULTS Twenty-nine trials (5,039 patients) were identified but were not pooled, because of considerable heterogeneity. A priori, we divided the interventions into homogeneous groups that were suitable for pooling. Strategies that incorporated follow-up by a specialized multidisciplinary team (either in a clinic or a non-clinic setting) reduced mortality (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.59 to 0.96), HF hospitalizations (RR 0.74, 95% CI 0.63 to 0.87), and all-cause hospitalizations (RR 0.81, 95% CI 0.71 to 0.92). Programs that focused on enhancing patient self-care activities reduced HF hospitalizations (RR 0.66, 95% CI 0.52 to 0.83) and all-cause hospitalizations (RR 0.73, 95% CI 0.57 to 0.93) but had no effect on mortality (RR 1.14, 95% CI 0.67 to 1.94). Strategies that employed telephone contact and advised patients to attend their primary care physician in the event of deterioration reduced HF hospitalizations (RR 0.75, 95% CI 0.57 to 0.99) but not mortality (RR 0.91, 95% CI 0.67 to 1.29) or all-cause hospitalizations (RR 0.98, 95% CI 0.80 to 1.20). In 15 of 18 trials that evaluated cost, multidisciplinary strategies were cost-saving. CONCLUSIONS Multidisciplinary strategies for the management of patients with HF reduce HF hospitalizations. Those programs that involve specialized follow-up by a multidisciplinary team also reduce mortality and all-cause hospitalizations. (C) 2004 by the American College of Cardiology Foundation.

A systematic review of laparoscopic live-donor nephrectomy

Background. A systematic review was undertaken to assess the safety and efficacy of laparoscopic live-donor nephrectomy (LLDN) compared with open live-donor nephrectomy (OLDN). Methods. Literature databases were searched from inception to March 2003 inclusive. Comparative studies of LLDN versus OLDN (randomized and nonrandomized) were included. Results. There were 44 included studies, and the quality of the available evidence was average. There was only one randomized controlled trial and six nonrandomized comparative studies with concurrent controls identified. In terms of safety, for donors, there did not seem to be any distinct difference between the laparoscopic and open approaches. No donor mortality was reported for either procedure, and the complication rates were similar although the types of complications experienced differed between the two procedures. The conversion rate for LLDN to an open procedure ranged from 0% to 13%. In terms of efficacy, LLDN seemed to be a slower operation with longer warm ischemia. times than OLDN, but this did not seem to have resulted in increased rates of delayed graft function for recipients. Donor postoperative recovery and convalescence seemed to be superior for LLDN, making it a potentially more attractive operation for living donors. Although in the short-term, graft function and survival did not seem to differ between the two techniques, long-term complication rates and allograft function could not be determined and further long-term follow-up is required. Conclusions. LLDN seems to be at least as safe and efficacious as OLDN in the short-term. However, it remains a technique in evolution. Further high-quality studies are required to resolve some of the outstanding issues surrounding its use, in particular, long-term follow-up of donor complications and recipient graft function and survival.

Early practical experience and the social responsiveness of clinical education: Systematic review

Objectives To find how early experience in clinical and community settings (early experience) affects medical education, and identify strengths and limitations of the available evidence. Design A systematic review rating, by consensus, the strength and importance of outcomes reported in the decade 1992-2001. Data sources Bibliographical databases and journals were searched for publications on the topic, reviewed under the auspices of the recently formed Best Evidence Medical Education (BEME) collaboration. Selection of studies All empirical studies (verifiable, observational data) were included, whatever their design, method, or language of publication. Results Early experience was most commonly provided in community settings, aiming to recruit primary care practitioners for underserved populations. It increased the popularity of primary care residencies, albeit among self selected students. It fostered self awareness and empathic attitudes towards ill people, boosted students' confidence, motivated them, gave them satisfaction, and helped them develop a professional identity. By helping develop interpersonal skills, it made entering clerkships a less stressful experience. Early experience helped students learn about professional roles and responsibilities, healthcare systems, and health needs of a population. It made biomedical, behavioural, and social sciences more relevant and easier to learn. It motivated and rewarded teachers and patients and enriched curriculums. In some countries,junior students provided preventive health care directly to underserved populations. Conclusion Early experience helps medical students learn, helps them develop appropriate attitudes towards their studies and future practice, and orientates medical curriculums towards society's needs. Experimental evidence of its benefit is unlikely to be forthcoming and yet more medical schools are likely to provide it. Effort could usefully be concentrated on evaluating the methods and outcomes of early experience provided within non-experimental research designs, and using that evaluation to improve the quality of curriculums.

Community-based programmes to prevent falls in children: A systematic review

Objective: We systematically reviewed the literature to examine the evidence for the effectiveness of community-based interventions to reduce fall-related injury in children aged 0-16 years. Methods: We performed a comprehensive search of the literature using the following study selection criteria: community-based intervention study; target population was children aged 0-16 years; outcome measure was fall-related injury rates; and either a community control or historical control was used in the study design. Quality assessment and data abstraction were guided by a standardized procedure and performed independently by two authors. Results: Only six studies fitting the inclusion criteria were identified in our search and only two of these used a trial design with a contemporary community control. Neither of the high quality evaluation studies showed an effect from the intervention and while authors of the remaining studies reported effective falls prevention programmes, the pre- and post-intervention design, uncontrolled for background secular trends, makes causal inferences from these studies difficult. Conclusion: There is a paucity of research studies from which evidence regarding the effectiveness of community-based intervention programmes for the prevention of fall-related injury in children could be based.

Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: A systematic review

Objective: To evaluate the efficacy of Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea. Data Sources: A computer-based search of MED-LINE, CINAHL, AMED, the Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews was conducted. A hand-search of the bibliographies of relevant papers and previous meta-analyses was undertaken. Review Methods: Trials were included in the review if they compared the effects of L. rhamnosus GG and placebo and listed diarrhoea as a primary end-point. Studies were excluded if they were not placebo-controlled or utilised other probiotic strains. Results:Six trials were found that met all eligibility requirements. Significant statistical heterogeneity of the trials precluded meta-analysis. Four of the six trials found a significant reduction in the risk of antibiotic-associated diarrhoea with co-administration of Lactobacillus GG. One of the trials found a reduced number of days with antibiotic-induced diarrhoea with Lactobacillus GG administration, whilst the final trial found no benefit of Lactobacillus GG supplementation. Conclusion: Additional research is needed to further clarify the effectiveness of Lactobacillus GG in the prevention of antibiotic-associated diarrhoea. Copyright (c) 2005 S. Karger AG, Basel.

Community-based programs to promote care seat restraints in children 0-16 years - A systematic review

Study Objective: Community-based models for injury prevention have become an accepted part of the overall injury control strategy. This systematic review of the scientific literature examines the evidence for their effectiveness in reducing injury due to inadequate car seat restraint use in children 0-16 years of age. Methods: A comprehensive search of the literature was performed using the following study selection criteria: community-based intervention study: target population was children aged 0-16 years of age; outcome measure was either injury rates due to motor vehicle crashes or observed changes in child restraint use; and use of community control or historical control in the study design. Quality assessment and data abstraction was guided by a standardized procedure and performed independently by two authors. Data synthesis was in tabular and text form with meta-analysis not being possible due to the discrepancy in methods and measures between the studies. Results: This review found eight studies, that met all the inclusion criteria. In the studies that measured injury outcomes, significant reductions in risk of motor vehicle occupant injury (33-55%) were reported in the study communities. For those studies reporting observed car seat restraint use the community-based programs were successful in increasing toddler restraint use in 1-5 year aged children by up to 11%; child booster seat use in 4-8 year aged children by up to 13%; rear restraint use in children aged 0-15 years by 8%; a 50% increase in restraint use in pre-school aged children in a high-risk community; and a 44% increase in children aged 5-11 years. Conclusion: While this review highlights that there is some evidence to support the effectiveness of community-based programs to promote car restraint use and/or motor vehicle occupant injury, limitations in the evaluation methodologies of the studies requires the results to be interpreted with caution. There is clearly a need for further high quality program evaluation research to develop an evidence base. (C) 2004 Elsevier Ltd. All rights reserved.