Citations

Background In 2005, the Endocrine Society (TES) adopted the GRADE system of developing clinical practice guidelines. This system facilitates the formulation of evidence-based recommendations by explicitly describing the confidence in estimates (quality of evidence) and strength of each recommendation. Objectives To describe and characterise the relationship between confidence in estimates and strength of recommendation in TES guidelines. Methods We included all published TES guidelines between 2005 (when TES started using GRADE) and 2011. Independently and in duplicate, reviewers extracted, for each recommendation: disease area, confidence in estimates and design of the studies considered, and strength of recommendation. In strong recommendations with low quality of we developed and applied a taxonomy of appropriate recommendations and identified those we considered inappropriate. Results Most of the 357 recommendations issued were supported by evidence warranting low or very low confidence in estimates (256, 72%). Evidence cited in support of these recommendations came exclusively from observational studies in 233 recommendations (65%). Most recommendations were strong (206, 58%); of these, 121 (59%) were supported by evidence warranting low or very low confidence in estimates. In 101/121 (83%), we identified a compelling rationale for the recommendations; in 20 (17%), we did not. Conclusions Most TES strong recommendation based on low quality evidence are justified and appropriate, but a substantial proportion are not. Implications for Guideline Developers Guideline developers should carefully justify any strong recommendations based on low confidence in effect estimates.

Abstract Background There is growing attention towards increasing patient and service user engagement ( PSUE ) in biomedical and health services research. Existing variations in language and design inhibit reporting and indexing, which are crucial to comparative effectiveness in determining best practices. Objective This paper utilizes a systematic review and environmental scan to derive an evidence‐based framework for PSUE . Design A metanarrative systematic review and environmental scan/manual search using scientific databases and other search engines, along with feedback from a patient advisory group ( PAG ). Eligible sources English‐language studies, commentaries, grey literature and other sources (including systematic and non‐systematic reviews) pertaining to patient and public involvement in biomedical and health services research. Data extracted Study description (e.g. participant demographics, research setting) and design, if applicable; frameworks, conceptualizations or planning schemes for PSUE ‐related endeavours; and methods for PSUE initiation and gathering patients'/service users' input or contributions. Results Overall, 202 sources were included and met eligibility criteria; 41 of these presented some framework or conceptualization of PSUE . Sources were synthesized into a two‐part framework for PSUE: (i) integral PSUE components include patient and service user initiation, reciprocal relationships, colearning and re‐assessment and feedback, (ii) sources describe PSUE at several research stages, within three larger phases: preparatory, execution and translational. Discussion and Conclusions Efforts at developing a solid evidence base on PSUE are limited by the non‐standard and non‐empirical nature of much of the literature. Our proposed two‐part framework provides a standard structure and language for reporting and indexing to support comparative effectiveness and optimize PSUE .

Background and Purpose— Use of endovascular coiling for treatment of ruptured and unruptured intracranial aneurysms (IAs) in the elderly is increasing. We performed a meta-analysis of the literature examining clinical and angiographic outcomes for treatment of IAs in the elderly. Methods— We performed a comprehensive review of the literature from 1995 to 2012, reporting series of patients ≥65 years of age with ruptured or unruptured IAs treated with endovascular approach. Event rates were pooled across studies using random effects meta-analysis. Results— A total of 21 studies reporting on 1511 patients were included. Long-term aneurysm occlusion rates were 79% (95% confidence interval [CI], 70%–85%). Perioperative stroke occurred in 4% (95% CI, 3%–6%), with similar rates between patients with ruptured (5%; 95% CI, 3%–7%) and unruptured aneurysms (4%; 95% CI, 1%–14%; P =0.68). Intraprocedural rupture occurred in 1% (95% CI, 0%–3%) and 4% (95% CI, 2–6%; P =0.04) of patients with unruptured and ruptured aneurysms, respectively. Perioperative mortality rate for patients with ruptured aneurysms was 23% (95% CI, 17%–30%) and 1% (95% CI, 0%–6%) for patients with unruptured aneurysms ( P <0.01). Rates of good clinical outcome at 1 year were 93% (95% CI, 88%–96%) and 66% (95% CI, 59%–72%) in patients with unruptured and ruptured aneurysms, respectively. Conclusions— This study suggests that endovascular treatment of IAs in the elderly is associated with high long-term occlusion rates. Given the morbidity and mortality associated with endovascular treatment of IAs in the elderly, careful patient selection, especially in the case of patients with unruptured aneurysm, is recommended.

AimTreatment of hepatitis C genotype 4 (HCV‐G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta‐analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR).MethodsWe searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta‐analysis was used to pool the risk ratio (RR) of achieving SVR across trials.ResultsFive RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR = 1.51, 95% confidence interval [CI] = 1.08–2.10). SVR was significantly higher in PEG IFN‐α‐2a compared to the ‐α‐2b group (P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR (P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity.ConclusionIn treatment‐naive patients with HCV‐G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.

AbstractAimsPioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta‐analysis to evaluate the magnitude of this association and the quality of the supporting evidence.MethodsElectronic databases were queried to identify controlled studies of pioglitazone that measured the risk of bladder cancer.ResultsSix studies involving 215 142 patients using pioglitazone were included, with a median period of follow‐up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09–1.39; I2 = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years.ConclusionsPatients treated with pioglitazone have a slight increased risk of bladder cancer compared to general population. Patient involvement and weighing treatment benefits versus risks should be discussed with patient toward shared decision. Patients with type 2 diabetes with risk factors, such as family history, smoking, or exposure to certain forms of chemotherapy may need to consider other anti‐hyperglycemic agents. Also, pioglitazone should be discontinued in type 2 diabetes patients with newly diagnosed bladder cancer.

Background and Purpose— Flow diverters are important tools in the treatment of intracranial aneurysms. However, their impact on aneurysmal occlusion rates, morbidity, mortality, and complication rates is not fully examined. Methods— We conducted a systematic review of the literature searching multiple databases for reports on the treatment of intracranial aneurysms with flow-diverter devices. Random effects meta-analysis was used to pool outcomes of aneurysmal occlusion rates at 6 months, and procedure-related morbidity, mortality, and complications across studies. Results— A total of 29 studies were included in this analysis, including 1451 patients with 1654 aneurysms. Aneurysmal complete occlusion rate was 76% (95% confidence interval [CI], 70%–81%). Procedure-related morbidity and mortality were 5% (95% CI, 4%–7%) and 4% (95% CI, 3%–6%), respectively. The rate of postoperative subarachnoid hemorrhage was 3% (95% CI, 2%–4%). Intraparenchymal hemorrhage rate was 3% (95% CI, 2%–4%). Perforator infarction rate was 3% (95% CI, 1%–5%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.01; 95% CI, 0.00–0.08; P <0.0001). Ischemic stroke rate was 6% (95% CI, 4%–9%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.15; 95% CI, 0.08–0.27; P <0.0001). Conclusions— This meta-analysis suggests that treatment of intracranial aneurysms with flow-diverter devices is feasible and effective with high complete occlusion rates. However, the risk of procedure-related morbidity and mortality is not negligible. Patients with posterior circulation aneurysms are at higher risk of ischemic stroke, particularly perforator infarction. These findings should be considered when considering the best therapeutic option for intracranial aneurysms.

BACKGROUNDCommunity‐acquired pneumonia (CAP) is a leading cause of morbidity and mortality among adults. Although steroids appear to be beneficial in animal models of CAP, clinical trial data in humans are either equivocal or conflicting.PURPOSEOur purpose was to perform a systematic review and meta‐analysis of studies examining the impact of steroid therapy on clinical outcomes among adults admitted with CAP.DATA SOURCES AND STUDY SELECTIONWe identified randomized controlled trials (RCTs) through a systematic search of published literature up to July 2011.DATA EXTRACTIONWe estimated relative risks (RR) and weighted mean differences, pooled from each study using a random effects model.DATA SYNTHESISEight RCTs, comprising 1119 patients, met our selection criteria. Overall quality of the studies was moderate. Adjunctive steroid therapy had no effect on hospital mortality or length of stay in the intensive care unit, but reduced the overall length of hospital stay (RR: −1.21 days [95% confidence interval (CI): −2.12 to −0.29]). Less robust data also demonstrated reduced incidence of delayed shock (RR: 0.12 [95% CI: 0.03 to 0.41]) and reduced persistence of chest x‐ray abnormalities (RR: 0.13 [95% CI: 0.06 to 0.27]). A priori subgroup and sensitivity analyses did not alter these findings.CONCLUSIONSModerate‐quality evidence suggests that adjunctive steroid therapy for adults hospitalized with CAP reduced the length of hospital stay but did not alter mortality. Journal of Hospital Medicine 2013;8:68–75. © 2012 Society of Hospital Medicine