Guidelines recommend a trial of one or more antiarrhythmic drugs before catheter ablation is considered in patients with atrial fibrillation. However, first-line ablation may be more effective in ...maintaining sinus rhythm.
We randomly assigned 303 patients with symptomatic, paroxysmal, untreated atrial fibrillation to undergo catheter ablation with a cryothermy balloon or to receive antiarrhythmic drug therapy for initial rhythm control. All the patients received an implantable cardiac monitoring device to detect atrial tachyarrhythmia. The follow-up period was 12 months. The primary end point was the first documented recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. The secondary end points included freedom from symptomatic arrhythmia, the atrial fibrillation burden, and quality of life.
At 1 year, a recurrence of atrial tachyarrhythmia had occurred in 66 of 154 patients (42.9%) assigned to undergo ablation and in 101 of 149 patients (67.8%) assigned to receive antiarrhythmic drugs (hazard ratio, 0.48; 95% confidence interval CI, 0.35 to 0.66; P<0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received antiarrhythmic drugs (hazard ratio, 0.39; 95% CI, 0.22 to 0.68). The median percentage of time in atrial fibrillation was 0% (interquartile range, 0 to 0.08) with ablation and 0.13% (interquartile range, 0 to 1.60) with antiarrhythmic drugs. Serious adverse events occurred in 5 patients (3.2%) who underwent ablation and in 6 patients (4.0%) who received antiarrhythmic drugs.
Among patients receiving initial treatment for symptomatic, paroxysmal atrial fibrillation, there was a significantly lower rate of atrial fibrillation recurrence with catheter cryoballoon ablation than with antiarrhythmic drug therapy, as assessed by continuous cardiac rhythm monitoring. (Funded by the Cardiac Arrhythmia Network of Canada and others; EARLY-AF ClinicalTrials.gov number, NCT02825979.).
The Cochrane risk of bias (CROB) tool and Physiotherapy Evidence Database (PEDro) scale are used to evaluate risk of bias of randomized controlled trials. We assessed the level of agreement between ...the instruments.
We searched the Cochrane Library to identify trials included in systematic reviews evaluating physical therapy interventions. For trials that met our inclusion criteria (primary reference in Cochrane review, review used CROB (2008 version), indexed in PEDro), CROB items were extracted from the reviews and PEDro items and total score were downloaded from PEDro. Kappa statistics were used to determine the agreement between CROB and PEDro scale items that evaluate similar constructs (e.g., randomization). The total PEDro score was compared to the CROB summary score (% of items met) using an Intraclass Correlation Coefficient. Sensitivity analyses explored the impact of the CROB "unclear" category and variants of CROB blinding items. Kappa statistics were used to determine agreement between different thresholds for "acceptable" risk of bias between CROB and PEDro scale summary scores.
We included 1442 trials from 108 Cochrane reviews. Agreement was "moderate" for three of the six CROB and PEDro scale items that evaluate similar constructs (allocation concealment, participant blinding, assessor blinding; Kappa = 0.479-0.582). Agreement between the summary scores was "poor" (Intraclass Correlation Coefficient = 0.285). Agreement was highest when the CROB "unclear" category was collapsed with "high" and when participant, personnel and assessor blinding were evaluated separately in CROB. Agreement for different thresholds for "acceptable" risk of bias between CROB and PEDro summary scores was, at best, "fair".
There was moderate agreement for half of the PEDro and CROB items that evaluate similar constructs. Interpretation of the CROB "unclear" category and variants of the CROB blinding items substantially influenced agreement. Either instrument can be used to quantify risk of bias, but they can't be used interchangeably.
Systematic reviews (SRs) of clinical practice guidelines (CPGs) are unique knowledge syntheses that require tailored approaches to, and greater subjectivity in, design and execution compared with ...other SRs in clinical epidemiology. We provide review authors structured direction on how to design and conduct methodologically rigorous SRs of CPGs.
A guidance paper outlining suggested methodology for conducting all stages of an SR of CPGs. We present concrete examples of approaches used by published reviews, including a case exemplar demonstrating how this methodology was applied to our own SR of CPGs.
Review context and the unique characteristics of CPGs as research syntheses or clinical guidance statements must be considered in all aspects of review design and conduct. Researchers should develop a “PICAR” statement to help form and focus on the research question(s) and eligibility criteria, assess CPG quality using a validated appraisal tool, and extract, analyze, and summarize data in a way that is cogent and transparent.
SRs of CPGs can be used to systematically identify, assess, and summarize the current state of guidance on a clinical topic. These types of reviews often require methodological tailoring to ensure that their objectives and timelines are effectively and efficiently addressed; however, they should all meet the criteria for an SR, follow a rigorous methodological approach, and adhere to transparent reporting practices.
An overview to the key summary of findings of the four paper series on what each paper adds to what was known and what is the implication and what should change now realted to the relative risk and ...odds ratio. Many interesting points and counterpoints have been raised by the authors of this Controversy and Debate series, confirming some of our understandings about the relative risk and odds ratio and shedding light on some aspects that may have been less clear. Through this series of four papers, they use probabilistic and statistical methods to present their point of view, and illustrate these points using a resource which has been likened to the health services equivalent of the Human Genome Project, 1,2 the Cochrane Collaboration; and extensively use the thousands of high-quality meta-analyses (MAs) that are housed in the Cochrane Database of Systematic Reviews (CDSR). ...they claim that the log link in regression models which generate RRs is problematic.
Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual ...treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD.
We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework.
Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration.
Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs.
PROSPERO no. CRD 42015026049.
Summary Background Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an ...increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs. Methods We did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included “biologics”, “rheumatoid arthritis” and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods. Findings The systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1·31, 95% credible interval CrI 1·09–1·58) and high-dose biological drugs (1·90, 1·50–2·39) were associated with an increased risk of serious infections, although low-dose biological drugs (0·93, 0·65–1·33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs. Interpretation Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. Funding Rheumatology Division at the University of Alabama at Birmingham.
We sought to assess the relative effects of individual anaplastic lymphoma kinase (ALK) inhibitors for the treatment of non-small cell lung cancer (NSCLC).
We searched MEDLINE, Embase, Cochrane ...CENTRAL, and grey literature (July 23, 2019) for randomized controlled trials (RCTs) that included participants with ALK- or ROS1-positive NSCLC who received any ALK inhibitor compared with placebo, another ALK inhibitor, or the same ALK inhibitor at a different dose. The primary outcome was treatment-related death. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and serious adverse events. Data were pooled via meta-analysis and network meta-analysis, and risk of bias was assessed. PROSPERO: CRD42017077046.
Thirteen RCTs reporting outcomes of interest among participants with ALK-positive NSCLC were identified. Treatment-related deaths were rare, with 10 deaths attributed to crizotinib (risk difference v. chemotherapy: 0.49, 95% credible interval CrI -0.16 to 1.46; odds ratio 2.58 (0.76-11.37). All ALK inhibitors improved PSF relative to chemotherapy (hazard ratio 95% CrI: crizotinib 0.46 0.39-0.54; ceritinib 0.52 0.42-0.64; alectinib 300 BID 0.16 0.08-0.33; alectinib 600 BID 0.23 0.17-0.30; brigatinib 0.23 0.15-0.35), while alectinib and brigatinib improved PFS over crizotinib and ceritinib (alectinib v. crizotinib 0.34 0.17-0.70; alectinib v. ceritinib 0.30 0.14-0.64; brigatinib v. crizotinib 0.49 0.33-0.73; brigatinib v. ceritinib 0.43 0.27-0.70). OS was improved with alectinib compared with chemotherapy (HR 0.57 95% CrI 0.39-0.83) and crizotinib (0.68 0.48-0.96). Use of crizotinib (odds ratio 2.08 95% CrI 1.56-2.79) and alectinib (1.60 1.00-2.58) but not ceritinib (1.25 0.90-1.74), increased the risk of serious adverse events compared with chemotherapy. Results were generally consistent among treatment-experienced or naïve participants.
Treatment-related deaths were infrequent among ALK-positive NSCLC. PFS may be improved by alectinib and brigatinib relative to other ALK inhibitors; however, the assessment of OS is likely confounded by treatment crossover and should be interpreted with caution.
Hypertension is a significant global public health problem and recognized as an important risk factor for cardiovascular diseases. This study was designed to assess the current prevalence of ...hypertension and to explore risk factors associated with hypertension by urban and rural status to guide the prevention and control of hypertension in Jilin province.
A multi-stage stratified random cluster sampling method was used to obtain data on hypertension, which was investigated by physical examination and face-to-face questionnaire in July 2014-December 2015. Sample data were analyzed by complex weighted statistical analysis to estimate blood pressure levels and prevalence of hypertension in the province. Multivariable logistic regression analysis was used to identify factors influencing hypertension rates.
The prevalence of hypertension was significantly higher in rural areas than urban areas (25.93% versus 22.73%, respectively). The rates of hypertension known (46.7% versus 38.1%, respectively), control (13.7% versus 5.0%, respectively), and controlled among treated subjects (38.3% versus 17.5%, respectively) were higher in urban areas than in rural areas (all p < 0.001), while the treatment rate was not statistically significantly different between urban and rural areas (35.9% versus 28.4%, respectively). After adjusting for demographic covariates, hypertension prevalence in rural areas was still significantly greater than in urban areas (adjusted OR = 1.22; 95%CI: 1.10, 1.36; p < 0.001). Common risk factors for hypertension among urban and rural residents included older age; male; married; employed; less education; overweight/obese; greater abdominal waist circumference; family history of hypertension, stroke, or coronary heart disease; current smoker; alcohol consumption; higher visceral adiposity index; and higher body fat percentage.
This study identified an increased risk for hypertension in rural regions of Jilin province, suggesting that rural hypertension screening and treatment guidelines should receive greater attention.
In clinical trials it is not uncommon to face a multiple testing problem which can have an impact on both type I and type II error rates, leading to inappropriate interpretation of trial results. ...Multiplicity issues may need to be considered at the design, analysis and interpretation stages of a trial. The proportion of trial reports not adequately correcting for multiple testing remains substantial. The purpose of this article is to provide an introduction to multiple testing issues in clinical trials, and to reduce confusion around the need for multiplicity adjustments. We use a tutorial, question-and-answer approach to address the key issues of why, when and how to consider multiplicity adjustments in trials. We summarize the relevant circumstances under which multiplicity adjustments ought to be considered, as well as options for carrying out multiplicity adjustments in terms of trial design factors including Population, Intervention/Comparison, Outcome, Time frame and Analysis (PICOTA). Results are presented in an easy-to-use table and flow diagrams. Confusion about multiplicity issues can be reduced or avoided by considering the potential impact of multiplicity on type I and II errors and, if necessary pre-specifying statistical approaches to either avoid or adjust for multiplicity in the trial protocol or analysis plan.
Our objective was to develop an instrument to assess the methodological quality of systematic reviews, building upon previous tools, empirical evidence and expert consensus.
A 37-item assessment tool ...was formed by combining 1) the enhanced Overview Quality Assessment Questionnaire (OQAQ), 2) a checklist created by Sacks, and 3) three additional items recently judged to be of methodological importance. This tool was applied to 99 paper-based and 52 electronic systematic reviews. Exploratory factor analysis was used to identify underlying components. The results were considered by methodological experts using a nominal group technique aimed at item reduction and design of an assessment tool with face and content validity.
The factor analysis identified 11 components. From each component, one item was selected by the nominal group. The resulting instrument was judged to have face and content validity.
A measurement tool for the 'assessment of multiple systematic reviews' (AMSTAR) was developed. The tool consists of 11 items and has good face and content validity for measuring the methodological quality of systematic reviews. Additional studies are needed with a focus on the reproducibility and construct validity of AMSTAR, before strong recommendations can be made on its use.
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