Abstract Anemia is common amongst patients undergoing percutaneous coronary intervention (PCI) and current guidelines fail to offer recommendations for its management. This review aims to examine the ...relationship between baseline anemia and mortality, Major Adverse Cardiovascular Events (MACE) and major bleeding in patients undergoing PCI. We searched MEDLINE and EMBASE for studies that evaluated mortality and adverse outcomes in anemic and non-anemic patients who underwent PCI. Data were collected on study design, participant characteristics, definition of anemia, follow up and adverse outcomes. Random effects meta-analysis of risk ratios was performed using inverse variance method. A total of 44 studies were included in the review with 230,795 participants. The prevalence of baseline anemia was 26,514/170,914 (16%). There was an elevated risk of mortality and MACE with anemia compared to no anemia pooled RR 2.39 (2.02-2.83), p<0.001 and RR 1.51 (1.34-1.71), p<0.001, respectively. The risk of myocardial infarction and bleeding with anemia compared to no anemia was elevated, pooled RR 1.33 (1.07-1.65), p=0.01 and RR 1.97 (1.03-3.77), p<0.001, respectively. The risk of mortality per unit incremental decrease in hemoglobin(g/dl) was RR 1.19 (1.09-1.30), p<0.001 and the risk of mortality, MACE and re-infarction per 1 unit incremental decrease in hematocrit(%) was RR 1.07 (1.05-1.10), p=0.04, RR 1.09 (1.08-1.10) and RR 1.06 (1.03-1.10), respectively. The prevalence of anemia in contemporary cohorts of patients undergoing PCI is significant and is associated with significant increases in post procedural mortality, MACE, re-infarction and bleeding. The optimal strategy for the management of anemia in such patients remains uncertain.
Rosiglitazone and pioglitazone may increase the incidence of fractures. We aimed to determine systematically the risk of fractures associated with thiazolidinedione therapy and to evaluate the effect ...of the therapy on bone density.
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), other trial registries and product information sheets through June 2008. We selected long-term (> or = 1 year) randomized controlled trials involving patients with type 2 diabetes and controlled observational studies that described the risk of fractures or changes in bone density with thiazolidinediones. We calculated pooled odds ratios (ORs) for fractures and the weighted mean difference in bone density.
We analyzed data from 10 randomized controlled trials involving 13 715 participants and from 2 observational studies involving 31 679 participants. Rosiglitazone and pioglitazone were associated with a significantly increased risk of fractures overall in the 10 randomized controlled trials (OR 1.45, 95% confidence interval CI 1.18-1.79; p < 0.001). Five randomized controlled trials showed a significantly increased risk of fractures among women (OR 2.23, 95% CI 1.65-3.01; p < 0.001) but not among men (OR 1.00, 95% CI 0.73-1.39; p = 0.98). The 2 observational studies demonstrated an increased risk of fractures associated with rosiglitazone and pioglitazone. Bone mineral density in women exposed to thiazolidinediones was significantly reduced at the lumbar spine (weighted mean difference -1.11%, 95% CI -2.08% to -0.14%; p = 0.02) and hip (weighted mean difference -1.24%, 95%CI -2.34% to -0.67%; p < 0.001) in 2 randomized controlled trials.
Long-term thiazolidinedione use doubles the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes.
Objective Hyperhomocysteinaemia is associated with peripheral arterial disease (PAD). There are inter-individual variations in the metabolism of homocysteine because of genetic polymorphisms. This ...study analyzed the role of one polymorphism that is associated with raised homocysteine, as a risk factor for PAD. Methods This study considered the association of methylenetetrahydrofolate reductase ( MTHFR ) C677T polymorphisms with the incidence of PAD by performing a case-control study and a cross sectional study of homocysteine levels. We recruited 133 patients with PAD in Norfolk and compared the MTHFR allele distribution with 457 healthy individuals. We also carried out a meta-analysis to place our data within the context of other published studies. We searched Medline, Embase, and Cochrane databases up to March 2008 for any studies on the association between MTHFR C677T polymorphism and PAD. Results The MTHFR C677T allele frequencies in the cases and controls were 0.37 and 0.33, and the odds ratios for the association of the 677 T allele or TT genotype with PAD were 1.18 (95% Confidence Interval CI 0.89, 1.58) and 1.99 (95% CI 1.09, 3.63). Homozygotes for the MTHFR C677T mutation had higher concentrations of plasma total homocysteine, odds ratio 2.82 (95% CI 1.03, 7.77) compared to homozygotes for the MTHFR 677 CC genotype. Twelve of 72 articles retrieved from the database search reported the prevalence of mutations in PAD patients. A meta-analysis of 9 appropriate studies, including our own, showed that being homozygous for the C677T allele was associated with an increased risk of PAD, pooled odds ratio 1.36 (95% CI 1.09, 1.68). Conclusion We have found a strong association between raised homocysteine, the TT genotype, and PAD.
Background Two different regimens of enoxaparin (40 mg once daily or 30 mg bid) have been used as control arms in trials of new oral anticoagulants. The choice of enoxaparin comparator may influence ...the perceived relative efficacy and safety of the newer agents, and we aimed to identify any significant differences between the two enoxaparin regimens. Methods We searched MEDLINE, EMBASE, and Cochrane Library for randomized controlled trials that compared enoxaparin to oral anticoagulant (apixaban, dabigatran, rivaroxaban) thromboprophylaxis in elective total knee or hip arthroplasty. Total VTE and bleeding events were pooled using fixed-effects meta-analysis and heterogeneity assessed with the I2 statistic. We conducted adjusted indirect comparisons of bid vs once-daily enoxaparin regimes based on new oral anticoagulants as common comparators. Results Fourteen randomized controlled trials in hip and knee replacement surgery met the inclusion criteria. Adjusted indirect comparison showed that bid enoxaparin was significantly more effective in preventing VTE than enoxaparin once daily (relative risk RR, 0.71; 95% CI, 0.61-0.83; P < .00001). For major and clinically relevant hemorrhage, adjusted indirect comparison showed that enoxaparin bid was nonsignificantly associated with increased risk of bleeding (RR 1.27; 95% CI, 0.97-1.65; P = .08) above that of enoxaparin once daily. Subgroup analysis limited to total knee arthroplasty trials showed similar results. Conclusions The use of once-daily enoxaparin regimen as control in clinical trials will lead to more favorable estimates of relative efficacy for the new oral anticoagulants than if enoxaparin 30 mg bid had been chosen as a comparator.
Abstract Objectives We sought to identify the proportion of systematic reviews of adverse effects which search for unpublished data and the success rates of identifying unpublished data for inclusion ...in a systematic review. Study Design and Setting Two reviewers independently screened all records published in 2014 in the Database of Abstracts of Reviews of Effects (DARE) for systematic reviews where the primary aim was to evaluate an adverse effect or effects. Data were extracted on the types of adverse effects and interventions evaluated, sources searched, how many unpublished studies were included and source or type of unpublished data included. Results From 9129 DARE abstracts, 348 met our inclusion criteria. Most of these reviews evaluated a drug intervention (237/348, 68%) with specified adverse effects (250/348, 72%). Over a third (136/348, 39%) of all the reviews searched a specific source for unpublished data, such as conference abstracts or trial registries and nearly half of these reviews (65/136, 48%) included unpublished data. An additional 13 reviews included unpublished data despite not searching specific sources for unpublished studies. Overall, 22% (78/348) of reviews included unpublished data/studies. Conclusion The majority of reviews of adverse effects do not search specifically for unpublished data but, of those that do, nearly half are successful.
Summary Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality ...variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.
Challenges in evaluating surgical innovation Ergina, Patrick L, Dr; Cook, Jonathan A, PhD; Blazeby, Jane M, Prof ...
Lancet,
09/2009, Letnik:
374, Številka:
9695
Journal Article
Recenzirano
Odprti dostop
Summary Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially ...demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.
Evaluation and stages of surgical innovations Barkun, Jeffrey S, Prof; Aronson, Jeffrey K, Prof; Feldman, Liane S, MD ...
The Lancet (British edition),
2009-Sep-26, Letnik:
374, Številka:
9695
Journal Article
Recenzirano
Summary Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and ...adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.
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