Nia Roberts

Anticoagulation Control and Prediction of Adverse Events in Patients With Atrial Fibrillation A Systematic Review

Background—To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation. Methods and Results—We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=−0.59; P=0.002) and thromboembolic rates (r=−0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=−0.78; P=0.006 and thromboembolic rate, r=−0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=−0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events). Conclusions—In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

A systematic review and meta-analysis: Probiotics in the treatment of irritable bowel syndrome

BackgroundIrritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence for efficacy of most drug therapies in the treatment of IBS is weak. A popular alternative is probiotics, which have been used in several conditions. including IBS. Probiotics are live microbial food supplements.The aim of this systematic review and meta-analysis of randomized trials study was to evaluate the efficacy of probiotics in alleviating symptoms in patients with irritable bowel syndrome. We searched Ovid versions of MEDLINE (1950–2007), EMBASE (1980–2007), CINAHL (1982–2007), AMED (1985–2007), the Cochrane library and hand searched retrieved papers.ResultsWe identified 14 randomized placebo controlled trials. Combined data suggested a modest improvement in overall symptoms after several weeks of treatment: for dichotomous data from seven trials the overall Odds Ratio (OR) was 1.6 (95% CI, 1.2 to 2.2); for continuous data from six trials the standardised mean difference (SMD) was 0.23 (95% CI, 0.07 to 0.38).For individual symptoms the results differed between the pooled dichotomous and pooled continuous data. Trials varied in relation to the length of treatment (4–26 weeks), dose, organisms and strengths of probiotics used.ConclusionProbiotics may have a role in alleviating some of the symptoms of IBS, a condition for which currently evidence of efficacy of drug therapies is weak. However, as IBS is a condition that is chronic and usually intermittent longer term trials are recommended. Such research should focus on the type, optimal dose of probiotics and the subgroups of patients who are likely to benefit the most.

Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: Systematic review

Objective To determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension. Design Systematic review with meta-analysis with hierarchical summary receiver operating characteristic models. Methodological quality was appraised, including evidence of validation of blood pressure measurement equipment. Data sources Medline (from 1966), Embase (from 1980), Cochrane Database of Systematic Reviews, DARE, Medion, ARIF, and TRIP up to May 2010. Eligibility criteria for selecting studies Eligible studies examined diagnosis of hypertension in adults of all ages using home and/or clinic blood pressure measurement compared with those made using ambulatory monitoring that clearly defined thresholds to diagnose hypertension. Results The 20 eligible studies used various thresholds for the diagnosis of hypertension, and only seven studies (clinic) and three studies (home) could be directly compared with ambulatory monitoring. Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% (95% confidence interval 60.7% to 84.8%) and 74.6% (47.9% to 90.4%), respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% (78.0% to 91.0%) and 62.4% (48.0% to 75.0%). Conclusions Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test. If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis. Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.

Anticoagulation Control and Prediction of Adverse Events in Patients With Atrial FibrillationCLINICAL PERSPECTIVE

Background—To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation. Methods and Results—We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=−0.59; P=0.002) and thromboembolic rates (r=−0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=−0.78; P=0.006 and thromboembolic rate, r=−0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=−0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events). Conclusions—In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

Systematic review and meta-analysis of reduction in all-cause mortality from walking and cycling and shape of dose response relationship

Background and objectiveWalking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA).Data sourcesWe conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews.Study eligibility criteria and participantsEligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible.Study appraisal and synthesis methodsExtracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling.ResultsWalking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose-response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose-response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval.Conclusions and implicationsThe analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact if they are able to increase walking and cycling levels in the groups that have the lowest levels of these activities.Review registrationThe review protocol was registered with PROSPERO (International database of prospectively registered systematic reviews in health and social care) PROSPERO 2013: CRD42013004266.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

Aims/hypothesisObservational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs).MethodsRCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I2statistics for heterogeneity were calculated by fixed effects meta-analysis.ResultsOf 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials.Conclusions/interpretationMeta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Evidence of effectiveness of health care professionals using handheld computers : a scoping review of systematic reviews

Background Handheld computers and mobile devices provide instant access to vast amounts and types of useful information for health care professionals. Their reduced size and increased processing speed has led to rapid adoption in health care. Thus, it is important to identify whether handheld computers are actually effective in clinical practice. Objective A scoping review of systematic reviews was designed to provide a quick overview of the documented evidence of effectiveness for health care professionals using handheld computers in their clinical work. Methods A detailed search, sensitive for systematic reviews was applied for Cochrane, Medline, EMBASE, PsycINFO, Allied and Complementary Medicine Database (AMED), Global Health, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. All outcomes that demonstrated effectiveness in clinical practice were included. Classroom learning and patient use of handheld computers were excluded. Quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. A previously published conceptual framework was used as the basis for dual data extraction. Reported outcomes were summarized according to the primary function of the handheld computer. Results Five systematic reviews met the inclusion and quality criteria. Together, they reviewed 138 unique primary studies. Most reviewed descriptive intervention studies, where physicians, pharmacists, or medical students used personal digital assistants. Effectiveness was demonstrated across four distinct functions of handheld computers: patient documentation, patient care, information seeking, and professional work patterns. Within each of these functions, a range of positive outcomes were reported using both objective and self-report measures. The use of handheld computers improved patient documentation through more complete recording, fewer documentation errors, and increased efficiency. Handheld computers provided easy access to clinical decision support systems and patient management systems, which improved decision making for patient care. Handheld computers saved time and gave earlier access to new information. There were also reports that handheld computers enhanced work patterns and efficiency. Conclusions This scoping review summarizes the secondary evidence for effectiveness of handheld computers and mhealth. It provides a snapshot of effective use by health care professionals across four key functions. We identified evidence to suggest that handheld computers provide easy and timely access to information and enable accurate and complete documentation. Further, they can give health care professionals instant access to evidence-based decision support and patient management systems to improve clinical decision making. Finally, there is evidence that handheld computers allow health professionals to be more efficient in their work practices. It is anticipated that this evidence will guide clinicians and managers in implementing handheld computers in clinical practice and in designing future research.

The need for randomization in animal trials: an overview of systematic reviews.

Background and Objectives Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition. Methods We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment. Results Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinsons disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective. Conclusions Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.

Can the London 2012 Olympics ‘inspire a generation’ to do more physical or sporting activities? An overview of systematic reviews

Objective To examine if there is an increased participation in physical or sporting activities following an Olympic or Paralympic games. Design Overview of systematic reviews. Methods We searched the Medline, Embase, Cochrane, DARE, SportDISCUS and Web of Knowledge databases. In addition, we searched for ‘grey literature’ in Google, Google scholar and on the International Olympic Committee websites. We restricted our search to those reviews published in English. We used the AMSTAR tool to assess the methodological quality of those systematic reviews included. Primary and secondary outcome measures The primary outcome was evidence for an increased participation in physical or sporting activities. Secondary outcomes included public perceptions of sport during and after an Olympic games, barriers to increased sports participation and any other non-sporting health benefits. Results Our systematic search revealed 844 citations, of which only two matched our inclusion criteria. The quality of these two reviews was assessed by three independent reviewers as ‘good’ using the AMSTAR tool for quality appraisal. Both reviews reported little evidence of an increased uptake of sporting activity following an Olympic Games event. Other effects on health, for example, changes in hospital admissions, suicide rates and drug use, were cited although there was insufficient evidence to see an overall effect. Conclusion There is a paucity of evidence to support the notion that hosting an Olympic games leads to an increased participation in physical or sporting activities for host countries. We also found little evidence to suggest other health benefits. We conclude that the true success of these and future games should be evaluated by high-quality, evidence-based studies that have been commissioned before, during and following the completion of the event. Only then can the true success and legacy of the games be established.

Quantifying the Effect of Metformin Treatment and Dose on Glycemic Control

OBJECTIVE Metformin is the first-line oral medication recommended for glycemic control in patients with type 2 diabetes. We reviewed the literature to quantify the effect of metformin treatment on glycated hemoglobin (HbA1c) levels in all types of diabetes and examine the impact of differing doses on glycemic control. RESEARCH DESIGN AND METHODS MEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks’ duration in which diabetic patients were treated with either metformin monotherapy or as an add-on therapy. Data on change in HbA1c were pooled in a meta-analysis. Data from dose-comparison trials were separately pooled. RESULTS A total of 35 trials were identified for the main analysis and 7 for the dose-comparison analysis. Metformin monotherapy lowered HbA1c by 1.12% (95% CI 0.92–1.32; I2 = 80%) versus placebo, metformin added to oral therapy lowered HbA1c by 0.95% (0.77–1.13; I2 = 77%) versus placebo added to oral therapy, and metformin added to insulin therapy lowered HbA1c by 0.60% (0.30–0.91; I2 = 79.8%) versus insulin only. There was a significantly greater reduction in HbA1c using higher doses of metformin compared with lower doses of metformin with no significant increase in side effects. CONCLUSIONS Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA1c used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.