John J. Riva

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics

BackgroundPrevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.ObjectiveThe World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.MethodsWe identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.ResultsCurrently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.ConclusionsWAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.

Risks and benefits of screening asymptomatic women for ovarian cancer: A systematic review and meta-analysis

OBJECTIVE We performed a systematic review and meta-analysis to quantify risks and benefits of screening asymptomatic women for ovarian cancer. METHODS We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL, without language restrictions, from January 1, 1979 to February 5, 2012. Eligible studies randomly assigned asymptomatic women to screening or usual care. Two reviewers independently screened studies for eligibility, extracted data using a standardized, piloted extraction form, and assessed bias and strength of inference for each outcome using the GRADE framework. Chance-corrected agreement was calculated at each step, and disagreements were resolved through consensus. RESULTS Ten randomized trials proved eligible. Screening did not reduce all-cause mortality (relative risk (RR)=1.0, 95% confidence interval (CI) 0.96-1.06), ovarian cancer specific mortality (RR=1.08, 95% CI 0.84-1.38), or risk of diagnosis at an advanced stage (RR of diagnosis at FIGO stages III-IV=0.86, 95% CI 0.68-1.11). Transvaginal ultrasound resulted in a mean of 38 surgeries per ovarian cancer detected (95% CI 15.7-178.1) while screening with CA-125 led to 4 surgeries per ovarian cancer detected (95% CI 2.7-4.5). Surgery was associated with severe complications in 6% of women (95% CI 1%-11%). Quality of life was not affected by screening; however, women with false-positive results had increased cancer-specific distress compared to those with normal results (odds ratio (OR)=2.22, 95% CI 1.23-3.99). CONCLUSIONS Screening asymptomatic women for ovarian cancer does not reduce mortality or diagnosis at an advanced stage and is associated with unnecessary surgery.

Comparisons of Interventions for Preventing Falls in Older Adults: A Systematic Review and Meta-analysis

Importance Falls result in substantial burden for patients and health care systems, and given the aging of the population worldwide, the incidence of falls continues to rise. Objective To assess the potential effectiveness of interventions for preventing falls. Data Sources MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Ageline databases from inception until April 2017. Reference lists of included studies were scanned. Study Selection Randomized clinical trials (RCTs) of fall-prevention interventions for participants aged 65 years and older. Data Extraction and Synthesis Pairs of reviewers independently screened the studies, abstracted data, and appraised risk of bias. Pairwise meta-analysis and network meta-analysis were conducted. Main Outcomes and Measures Injurious falls and fall-related hospitalizations. Results A total of 283 RCTs (159 910 participants; mean age, 78.1 years; 74% women) were included after screening of 10 650 titles and abstracts and 1210 full-text articles. Network meta-analysis (including 54 RCTs, 41 596 participants, 39 interventions plus usual care) suggested that the following interventions, when compared with usual care, were associated with reductions in injurious falls: exercise (odds ratio [OR], 0.51 [95% CI, 0.33 to 0.79]; absolute risk difference [ARD], −0.67 [95% CI, −1.10 to −0.24]); combined exercise and vision assessment and treatment (OR, 0.17 [95% CI, 0.07 to 0.38]; ARD, −1.79 [95% CI, −2.63 to −0.96]); combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30 [95% CI, 0.13 to 0.70]; ARD, −1.19 [95% CI, −2.04 to −0.35]); and combined clinic-level quality improvement strategies (eg, case management), multifactorial assessment and treatment (eg, comprehensive geriatric assessment), calcium supplementation, and vitamin D supplementation (OR, 0.12 [95% CI, 0.03 to 0.55]; ARD, −2.08 [95% CI, −3.56 to −0.60]). Pairwise meta-analyses for fall-related hospitalizations (2 RCTs; 516 participants) showed no significant association between combined clinic- and patient-level quality improvement strategies and multifactorial assessment and treatment relative to usual care (OR, 0.78 [95% CI, 0.33 to 1.81]). Conclusions and Relevance Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of fall-prevention intervention may depend on patient and caregiver values and preferences.

Systematic review and network meta-analysis of interventions for fibromyalgia: a protocol

BackgroundFibromyalgia is associated with substantial socioeconomic loss and, despite considerable research including numerous randomized controlled trials (RCTs) and systematic reviews, there exists uncertainty regarding what treatments are effective. No review has evaluated all interventional studies for fibromyalgia, which limits attempts to make inferences regarding the relative effectiveness of treatments.Methods/designWe will conduct a network meta-analysis of all RCTs evaluating therapies for fibromyalgia to determine which therapies show evidence of effectiveness, and the relative effectiveness of these treatments. We will acquire eligible studies through a systematic search of CINAHL, EMBASE, MEDLINE, AMED, HealthSTAR, PsychINFO, PapersFirst, ProceedingsFirst, and the Cochrane Central Registry of Controlled Trials. Eligible studies will randomly allocate patients presenting with fibromyalgia or a related condition to an intervention or a control. Teams of reviewers will, independently and in duplicate, screen titles and abstracts and complete full text reviews to determine eligibility, and subsequently perform data abstraction and assess risk of bias of eligible trials. We will conduct meta-analyses to establish the effect of all reported therapies on patient-important outcomes when possible. To assess relative effects of treatments, we will construct a random effects model within the Bayesian framework using Markov chain Monte Carlo methods.DiscussionOur review will be the first to evaluate all treatments for fibromyalgia, provide relative effectiveness of treatments, and prioritize patient-important outcomes with a focus on functional gains. Our review will facilitate evidence-based management of patients with fibromyalgia, identify key areas for future research, and provide a framework for conducting large systematic reviews involving indirect comparisons.

Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis

Background: It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did (“insiders”) and did not (“outsiders”) enter RCTs, without regard to the specific therapies received for their respective diagnoses. Methods: By searching the MEDLINE (1966–2010), Embase (1980–2010), CENTRAL (1960–2010) and PsycINFO (1880–2010) databases, we identified 147 studies that reported the health outcomes of “insiders” and a group of parallel or consecutive “outsiders” within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients’ outcomes. Results: We found no clinically or statistically significant differences in outcomes between “insiders” and “outsiders” in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes −0.03, 95% confidence interval [CI] −0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both “insiders” and “outsiders” (mean difference 0.04, 95% CI −0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by “insiders,” the “outsiders” experienced significantly worse health outcomes (mean difference −0.36, 95% CI −0.61 to −0.12). Interpretation: We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.

Reporting of IMMPACT-recommended core outcome domains among trials assessing opioids for chronic non-cancer pain.

Abstract The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that trialists evaluating treatments for chronic pain should consider reporting 9 patient-important outcome domains. We examined the extent to which clinical trials evaluating the effect of opioids for chronic non-cancer pain (CNCP) report outcome domains recommended by IMMPACT. We systematically searched electronic databases for English-language studies that randomized patients with CNCP to receive an opioid or a non-opioid control. In duplicate and independently, reviewers established the eligibility of each identified study and recorded all reported outcome domains from eligible trials. We conducted a priori regression analyses to explore factors that may be associated with IMMPACT-recommended outcome domains. Among 156 eligible trials, reporting of IMMPACT-recommended outcome domains was highly variable, ranging from 99% for pain to 7% for interpersonal functioning. Recently published trials were more likely to report the effect of treatment on physical functioning, emotional functioning, role functioning, sleep and fatigue, and participant disposition. Trials for which the corresponding author was from North America were more likely to report treatment effects on physical functioning and participant ratings of improvement and satisfaction with treatment. Trials published in higher impact journals were more likely to report treatment effects on emotional function, but less likely to report participant ratings of improvement and satisfaction with treatment. Most IMMPACT domains showed an increased rate of reporting over time, although many patient-important outcome domains remained unreported by over half of all trials evaluating the effects of opioids for CNCP.

Using patient values and preferences to inform the importance of health outcomes in practice guideline development following the GRADE approach

BackgroundThere are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development.MethodsIn 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives.ResultsWe found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences.ConclusionsCurrently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings.

The Saudi clinical practice guideline for the management of overweight and obesity in adults

Objective: To assist healthcare providers in evidence-based clinical decision-making for the management of overweight and obese adults in Saudi Arabia. Methods: The Ministry of Health, Riyadh, Kingdom of Saudi Arabia assembled an expert Saudi panel to produce this clinical practice guideline in 2015. In collaboration with the methodological working group from McMaster University, Hamilton, Canada, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which describes both the strength of recommendation and the quality of evidence Results: After identifying 11 questions, corresponding recommendations were agreed upon as guidance for the management of overweight and obese adults. These included strong recommendations in support of lifestyle interventions rather than usual care alone, individualized counseling interventions rather than generic educational pamphlets, physical activity rather than no physical activity, and physical activity in addition to diet rather than diet alone. Metformin and orlistat were suggested as conditional recommendations for the management of overweight and obesity in adults. Bariatric surgery was recommended, conditionally, for the management of obese adults (body mass index of ≥40 or ≥35 kg/m2 with comorbidities). Conclusions: The current guideline includes recommendation for the non-pharmacological, pharmacological, and surgical management of overweight and obese adults. In addition, the panel recommends conducting research priorities regarding lifestyle interventions and economic analysis of drug therapy within the Saudi context, as well as long term benefits and harms of bariatric surgery.

Opioids for chronic non-cancer pain: a protocol for a systematic review of randomized controlled trials

BackgroundOpioids are prescribed frequently and increasingly for the management of chronic non-cancer pain (CNCP). Current systematic reviews have a number of limitations, leaving uncertainty with regard to the benefits and harms associated with opioid therapy for CNCP. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using opioids in the treatment of CNCP and the risk of associated adverse events.Methods and designEligible trials will include those that randomly allocate patients with CNCP to treatment with any opioid or any non-opioid control group. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. To ensure interpretability of our results, we will present risk differences and measures of relative effect for all outcomes reported and these will be based on anchor-based minimally important clinical differences, when available. We will conduct a priori defined subgroup analyses consistent with current best practices.DiscussionOur review will evaluate both the effectiveness and the adverse events associated with opioid use for CNCP, evaluate confidence in the evidence using the GRADE approach, and prioritize patient-important outcomes with a focus on functional gains guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with CNCP and identify key areas for future research.Systematic review registrationOur protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.

Patients’ Attitudes Toward Nonphysician Screening of Low Back and Low Back Related Leg Pain Complaints Referred for Surgical Assessment

Study Design. A questionnaire survey. Objective. The aim of this study was to explore patient attitudes toward screening to assess suitability for low back surgery by nonphysician health care providers. Summary of Background Data. Canadian spine surgeons have shown support for nonphysician screening to assess and triage patients with low back pain and low back related leg pain. However, patients’ attitudes toward this proposed model are largely unknown. Methods. We administered a 19-item cross-sectional survey to adults with low back and/or low back related leg pain who were referred for elective surgical assessment at one of five spine surgeons’ clinics in Hamilton, Ontario, Canada. The survey inquired about demographics, expectations regarding wait time for surgical consultation, as well as willingness to pay, travel, and be screened by nonphysician health care providers. Results. Eighty low back patients completed our survey, for a response rate of 86.0% (80 of 93). Most respondents (72.5%; 58 of 80) expected to be seen by a surgeon within 3 months of referral, and 88.8% (71 of 80) indicated willingness to undergo screening with a nonphysician health care provider to establish whether they were potentially a surgical candidate. Half of respondents (40 of 80) were willing to travel >50 km for assessment by a nonphysician health care provider, and 46.2% were willing to pay out-of-pocket (25.6% were unsure). However, most respondents (70.0%; 56 of 80) would still want to see a surgeon if they were ruled out as a surgical candidate, and written comments from respondents revealed concern regarding agreement between surgeons’ and nonphysicians’ determination of surgical candidates. Conclusion. Patients referred for surgical consultation for low back or low back related leg pain are largely willing to accept screening by nonphysician health care providers. Future research should explore the concordance of screening results between surgeon and nonphysician health care providers. Level of Evidence: 3