Abstract Objective To develop ROBIS, a new tool for assessing the risk of bias in systematic reviews (rather than in primary studies). Study Design and Setting We used four-stage approach to develop ...ROBIS: define the scope, review the evidence base, hold a face-to-face meeting, and refine the tool through piloting. Results ROBIS is currently aimed at four broad categories of reviews mainly within health care settings: interventions, diagnosis, prognosis, and etiology. The target audience of ROBIS is primarily guideline developers, authors of overviews of systematic reviews (“reviews of reviews”), and review authors who might want to assess or avoid risk of bias in their reviews. The tool is completed in three phases: (1) assess relevance (optional), (2) identify concerns with the review process, and (3) judge risk of bias. Phase 2 covers four domains through which bias may be introduced into a systematic review: study eligibility criteria; identification and selection of studies; data collection and study appraisal; and synthesis and findings. Phase 3 assesses the overall risk of bias in the interpretation of review findings and whether this considered limitations identified in any of the phase 2 domains. Signaling questions are included to help judge concerns with the review process (phase 2) and the overall risk of bias in the review (phase 3); these questions flag aspects of review design related to the potential for bias and aim to help assessors judge risk of bias in the review process, results, and conclusions. Conclusions ROBIS is the first rigorously developed tool designed specifically to assess the risk of bias in systematic reviews.
The number of published systematic reviews of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions. Systematic reviews are ...subject to a range of biases and increasingly include non-randomised studies of interventions. It is important that users can distinguish high quality reviews. Many instruments have been designed to evaluate different aspects of reviews, but there are few comprehensive critical appraisal instruments. AMSTAR was developed to evaluate systematic reviews of randomised trials. In this paper, we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic reviews, including those based on non-randomised studies of healthcare interventions.
Large representative cohorts can provide compelling descriptions of variation in both health care practice and health outcomes, and their value is often underestimated. Such information is vital to ...health policy-makers for planning services, but also to clinicians and researchers, as substantial variation often represents an opportunity to target improvements in practice and influence future outcomes. Here, Reeves highlights the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation study where researchers report rates of perioperative mortality and serious complications after surgery among people undergoing surgery and requiring at least 1 night in hospital, and associations between complications and 30-day mortality adjusted for baseline comorbidities.
Summary Background Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related ...choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. Methods In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. Findings Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference −1·37 letters, 95% CI −3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (−1·63 letters, −4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 6% of 314 participants) and bevacizumab (12 4% of 296; odds ratio OR 1·69, 95% CI 0·80–3·57; p=0·16), or those given continuous (12 4% of 308) and discontinuous treatment (20 7% of 302; 0·56, 0·27–1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22–1·03; p=0·05), but did not differ by drug group (0·96, 0·46–2·02; p=0·91). Interpretation Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought. Funding UK National Institute for Health Research Health Technology Assessment programme.
In this study, patients were randomly assigned to a transfusion threshold of 9 or 7.5 g per deciliter after cardiac surgery. There was no significant between-group difference in infectious or ...ischemic events, but more deaths were associated with the lower threshold.
Perioperative anemia is common after cardiac surgery and is associated with significant increases in morbidity and mortality.
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The transfusion of allogeneic red cells is the preferred treatment for acute anemia and is also used in patients undergoing cardiac surgery; typically, more than 50% of patients receive a perioperative transfusion,
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which uses a substantial proportion of blood supplies.
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Observational studies suggest that transfusion is harmful after cardiac surgery; associations have been reported between transfusion and infection, low cardiac output, acute kidney injury, and death.
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In contrast, randomized, controlled trials of red-cell transfusion with restrictive thresholds (i.e., transfusions . . .
Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely ...unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage.
The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.
The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane ...risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
Health interventions fall along a spectrum from simple to more complex. There is wide interest in methods for reviewing 'complex interventions', but few transparent approaches for assessing ...intervention complexity in systematic reviews. Such assessments may assist review authors in, for example, systematically describing interventions and developing logic models. This paper describes the development and application of the intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR), a new tool to assess and categorise levels of intervention complexity in systematic reviews.
We developed the iCAT_SR by adapting and extending an existing complexity assessment tool for randomized trials. We undertook this adaptation using a consensus approach in which possible complexity dimensions were circulated for feedback to a panel of methodologists with expertise in complex interventions and systematic reviews. Based on these inputs, we developed a draft version of the tool. We then invited a second round of feedback from the panel and a wider group of systematic reviewers. This informed further refinement of the tool.
The tool comprises ten dimensions: (1) the number of active components in the intervention; (2) the number of behaviours of recipients to which the intervention is directed; (3) the range and number of organizational levels targeted by the intervention; (4) the degree of tailoring intended or flexibility permitted across sites or individuals in applying or implementing the intervention; (5) the level of skill required by those delivering the intervention; (6) the level of skill required by those receiving the intervention; (7) the degree of interaction between intervention components; (8) the degree to which the effects of the intervention are context dependent; (9) the degree to which the effects of the interventions are changed by recipient or provider factors; (10) and the nature of the causal pathway between intervention and outcome. Dimensions 1-6 are considered 'core' dimensions. Dimensions 7-10 are optional and may not be useful for all interventions.
The iCAT_SR tool facilitates more in-depth, systematic assessment of the complexity of interventions in systematic reviews and can assist in undertaking reviews and interpreting review findings. Further testing of the tool is now needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having ...cardiac surgery.
Clinical, hematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were prespecified as coprimary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modeling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus nontransfused patients were 3.38 (95% confidence interval CI, 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times 95% CI, 1.37 to 1.46, varying from 1.11 for 1 U to 3.35 for >9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio HR, 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; >1 year: HR, 1.32; 95% CI, 1.08 to 1.64).
Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.
To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD).
Multicenter, noninferiority factorial trial ...with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560).
People >50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart.
We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review.
The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs.
Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval CI, -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio GMR, 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio OR, 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001).
The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.
Proprietary or commercial disclosures may be found after the references.
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