Showing papers by "Gordon H. Guyatt published in 2016"

Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage

Abstract: Importance More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion–dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: Conclusions and Relevance Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines

Abstract: #### Summary points Clinicians regularly face situations with two or more alternative actions. Each alternative often has different advantages and disadvantages, including differences in effectiveness, adverse effects, costs and other factors …

When and how to update systematic reviews: consensus and checklist.

Abstract: Updating of systematic reviews is generally more efficient than starting all over again when new evidence emerges, but to date there has been no clear guidance on how to do this. This guidance helps authors of systematic reviews, commissioners, and editors decide when to update a systematic review, and then how to go about updating the review.

Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies

Abstract: Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer. Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case–control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase. Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24–1.48), radiotherapy (OR 1.35, 95% CI 1.16–1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73–3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03–1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01–1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy. Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery.

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies

Abstract: Objectives To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Design Systematic review and meta-analysis of randomised and observational studies. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Eligibility criteria Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Data collection and analysis Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Results Eligible studies included 43 trials (n=68 775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1 777 358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15 701 v 33/12 591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18 554 v 552/18 474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. Conclusions The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use.

Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis

Abstract: Background For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. Methods A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference −2·6 (95 per cent c.i. –6·3 to 1·1) per cent (low-quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference −7·2 (−18·1 to 3·8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. Conclusion The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value- and preference-dependent, suggesting a change in practice towards shared decision-making is necessary.

Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies

Abstract: Objective To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis. Design Systematic review and meta-analysis of observational studies. Data sources Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016. Study selection Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years. Methods Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay. Results In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15). Conclusion Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years.

Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta-analysis

Abstract: Objective To examine the effect of transcatheter aortic valve implantation (TAVI) versus surgical replacement of an aortic valve (SAVR) in patients with severe aortic stenosis at low and intermediate risk of perioperative death. Design Systematic review and meta-analysis Data sources Medline, Embase, and Cochrane CENTRAL. Study selection Randomized trials of TAVI compared with SAVR in patients with a mean perioperative risk of death Review methods Two reviewers independently extracted data and assessed risk of bias for outcomes important to patients that were selected a priori by a parallel guideline committee, including patient advisors. We used the GRADE system was used to quantify absolute effects and quality of evidence. Results 4 trials with 3179 patients and a median follow-up of two years were included. Compared with SAVR, transfemoral TAVI was associated with reduced mortality (risk difference per 1000 patients: −30, 95% confidence interval −49 to −8, moderate certainty), stroke (−20, −37 to 1, moderate certainty), life threatening bleeding (−252, −293 to −190, high certainty), atrial fibrillation (−178, −150 to −203, moderate certainty), and acute kidney injury (−53, −39 to −62, high certainty) but increased short term aortic valve reintervention (7, 1 to 21, moderate certainty), permanent pacemaker insertion (134, 16 to 382, moderate certainty), and moderate or severe symptoms of heart failure (18, 5 to 34, moderate certainty). Compared with SAVR, transapical TAVI was associated higher mortality (57, −16 to 153, moderate certainty, P=0.015 for interaction between transfemoral versus transapical TAVI) and stroke (45, −2 to 125, moderate certainty, interaction P=0.012). No study reported long term follow-up, which is particularly important for structural valve deterioration. Conclusions Many patients, particularly those who have a shorter life expectancy or place a lower value on the risk of long term valve degeneration, are likely to perceive net benefit with transfemoral TAVI versus SAVR. SAVR, however, performs better than transapical TAVI, which is of interest to patients who are not candidates for transfemoral TAVI. Systematic review registration PROSPERO CRD42016042879

Introduction to BMJ Rapid Recommendations

Abstract: New BMJ collaboration accelerates evidence into practice to answer the questions that matter quickly and transparently through trustworthy recommendations

Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials

Abstract: The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill. We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome. In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I 2 = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I 2 = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I 2 = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I 2 = 0 %, moderate confidence), or ICU length of stay (mean difference (MD), –0.38 days; 95 % CI –1.49, 0.74; P = 0.51; I 2 = 30 %, low confidence). No RCT reported Clostridium difficile infection. PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.

Toward Fairness in Data Sharing.

Abstract: From the Section of Cardiovascular Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale School of Medicine, the Center for Outcomes Research and Evaluation, Yale New Haven Hospital, and the Department of Health Policy and Management, Yale School of Public Health — all in New Haven, CT (H.M.K.); and Johnson & Johnson, New Brunswick, NJ ( J.W.).

Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline

Abstract: In patients with symptomatic severe aortic stenosis but at lower risk of perioperative death, how do minimally invasive techniques compare with open surgery? Prompted by a recent trial, an expert panel produced these recommendations based on three linked rapid systematic reviews

Do clinicians understand the size of treatment effects? A randomized survey across 8 countries

Abstract: Background: Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions. The interpretation of the magnitude of these differences — from trivial to large — can, however, be challenging. We investigated clinicians’ understanding and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses (standardized mean difference, minimal important difference units, mean difference in natural units, ratio of means, relative risk and risk difference). Methods: We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate. Paper-based, self-administered questionnaires presented summary estimates of hypothetical interventions versus placebo for chronic pain. The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes. Questions addressed participants’ understanding of the magnitude of treatment effects and their perception of the usefulness of the presentation format. We randomly assigned participants 1 of 4 versions of the questionnaire, each with a different effect size (large or small) and presentation order for the 6 formats (1 to 6, or 6 to 1). Results: Overall, 531 (87.0%) of the clinicians responded. Respondents best understood risk difference, followed by relative risk and ratio of means. Similarly, they perceived the dichotomous presentation of continuous outcomes (relative risk and risk difference) to be most useful. Presenting results as a standardized mean difference, the longest standing and most widely used approach, was poorly understood and perceived as least useful. Interpretation: None of the presentation formats were well understood or perceived as extremely useful. Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful. Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed.

Requirements of Clinical Journals for Authors' Disclosure of Financial and Non-Financial Conflicts of Interest: A Cross Sectional Study.

Abstract: Importance It is unclear how medical journals address authors’ financial and non-financial conflict of interest (COI). Objective To assess the policies of clinical journals for disclosure of financial and non-financial COI. Methods Cross sectional study that included both review of public documents as well as a simulation of a manuscript submission for the National Library of Medicine’s “core clinical journals”. The study did not involve human subjects. Investigators who abstracted the data, reviewed “instructions for authors” on the journal website and, in order to reflect the actual implementation of the COI disclosure policy, simulated the submission of a manuscript. Two individuals working in duplicate and independently to abstract information using a standardized data abstraction form, resolved disagreements by discussion or with the help of a third person. Results All but one of 117 core clinical journals had a COI policy. All journals required disclosure of financial COI pertaining to the authors and a minority (35%) asked for financial COI disclosure pertaining to the family members or authors' institution (29%). Over half required the disclosure of at least one form of non-financial COI (57%), out of which only two (3%) specifically referred to intellectual COI. Small minorities of journals (17% and 24% respectively) described a potential impact of disclosed COI and of non-disclosure of COI on the editorial process. Conclusion While financial COI disclosure was well defined by the majority of the journals, many did not have clear policies on disclosure of non-financial COI, disclosure of financial COI of family members and institutions of the authors, and effect of disclosed COI or non-disclosure of COI on editorial policies.

Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial

Abstract: Objective To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures Design A concealed, randomized, blinded, sham controlled clinical trial with a parallel group design of 501 patients, enrolled between October 2008 and September 2012, and followed for one year Setting 43 North American academic trauma centers Participants Skeletally mature men or women with an open or closed tibial fracture amenable to intramedullary nail fixation Exclusions comprised pilon fractures, tibial shaft fractures that extended into the joint and required reduction, pathological fractures, bilateral tibial fractures, segmental fractures, spiral fractures >75 cm in length, concomitant injuries that were likely to impair function for at least as long as the patient’s tibial fracture, and tibial fractures that showed 1 cm gap after surgical fixation 3105 consecutive patients who underwent intramedullary nailing for tibial fracture were assessed, 599 were eligible and 501 provided informed consent and were enrolled Interventions Patients were allocated centrally to self administer daily LIPUS (n=250) or use a sham device (n=251) until their tibial fracture showed radiographic healing or until one year after intramedullary fixation Main outcome measures Primary registry specified outcome was time to radiographic healing within one year of fixation; secondary outcome was rate of non-union Additional protocol specified outcomes included short form-36 (SF-36) physical component summary (PCS) scores, return to work, return to household activities, return to ≥80% of function before injury, return to leisure activities, time to full weight bearing, scores on the health utilities index (mark 3), and adverse events related to the device Results SF-36 PCS data were acquired from 481/501 (96%) patients, for whom we had 2303/2886 (80%) observations, and radiographic healing data were acquired from 482/501 (96%) patients, of whom 82 were censored Results showed no impact on SF-36 PCS scores between LIPUS and control groups (mean difference 055, 95% confidence interval −075 to 184; P=041) or for the interaction between time and treatment (P=030); minimal important difference is 3-5 points) or in other functional measures There was also no difference in time to radiographic healing (hazard ratio 107, 95% confidence interval 086 to 134; P=055) There were no differences in safety outcomes between treatment groups Patient compliance was moderate; 73% of patients administered ≥50% of all recommended treatments Conclusions Postoperative use of LIPUS after tibial fracture fixation does not accelerate radiographic healing and fails to improve functional recovery Study registration ClinicalTrialGov Identifier: [NCT00667849][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00667849&atom=%2Fbmj%2F355%2Fbmji5351atom

Guideline of guidelines: thromboprophylaxis for urological surgery

Abstract: Decisions regarding thromboprophylaxis in urologic surgery involve a trade-off between decreased risk of venous thromboembolism (VTE) and increased risk of bleeding. Both patient- and procedure-specific factors are critical in making an informed decision on the use of thromboprophylaxis. Our systematic review of the literature revealed that existing guidelines in urology are limited. Recommendations from national and international guidelines often conflict and are largely based on indirect as opposed to procedure-specific evidence. These issues have likely contributed to large variation in the use of VTE prophylaxis within and between countries. The majority of existing guidelines typically suggest prolonged thromboprophylaxis for high-risk abdominal or pelvic surgery, without clear clarification of what these procedures are, for up to 4 weeks post-discharge. Existing guidance may result in the under-treatment of procedures with low risk of bleeding and the over-treatment of oncological procedures with low risk of VTE. Guidance for patients who are already anticoagulated are not specific to urological procedures but generally involve evaluating patient and surgical risks when deciding on bridging therapy. The European Association of Urology Guidelines Office has commissioned an ad hoc guideline panel that will present a formal thromboprophylaxis guideline for specific urological procedures and patient risk factors.

Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis

Abstract: Background Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents—phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD.