Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline.

BACKGROUND: Gout is a common type of inflammatory arthritis in patients seen by primary care physicians. PURPOSE: To review evidence about treatment of acute gout attacks, management of hyperuricemia to prevent attacks, and discontinuation of medications for chronic gout in adults. DATA SOURCES: Multiple electronic databases from January 2010 to March 2016, reference mining, and pharmaceutical manufacturers. STUDY SELECTION: Studies of drugs approved by the U.S. Food and Drug Administration and commonly prescribed by primary care physicians, randomized trials for effectiveness, and trials and observational studies for adverse events. DATA EXTRACTION: Data extraction was performed by one reviewer and checked by a second reviewer. Study quality was assessed by 2 independent reviewers. Strength-of-evidence assessment was done by group discussion. DATA SYNTHESIS: High-strength evidence from 28 trials (only 3 of which were placebo-controlled) shows that colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids reduce pain in patients with acute gout. Moderate-strength evidence suggests that low-dose colchicine is as effective as high-dose colchicine and causes fewer gastrointestinal adverse events. Moderate-strength evidence suggests that urate-lowering therapy (allopurinol or febuxostat) reduces long-term risk for acute gout attacks after 1 year or more. High-strength evidence shows that prophylaxis with daily colchicine or NSAIDs reduces the risk for acute gout attacks by at least half in patients starting urate-lowering therapy, and moderate-strength evidence indicates that duration of prophylaxis should be longer than 8 weeks. Although lower urate levels reduce risk for recurrent acute attacks, treatment to a specific target level has not been tested. LIMITATION: Few studies of acute gout treatments, no placebo-controlled trials of management of hyperuricemia lasting longer than 6 months, and few studies in primary care populations. CONCLUSION: Colchicine, NSAIDs, and corticosteroids relieve pain in adults with acute gout. Urate-lowering therapy decreases serum urate levels and reduces risk for acute gout attacks. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol registration: http://effectivehealth-care.ahrq.gov/ehc/products/564/1992/Gout-managment-protocol-141103.pdf).

Diagnosis of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline.

BACKGROUND: Alternative strategies exist for diagnosing gout that do not rely solely on the documentation of monosodium urate (MSU) crystals. PURPOSE: To summarize evidence regarding the accuracy of clinical tests and classification algorithms compared with that of a reference standard of MSU crystals in joint aspirate for diagnosing gout. DATA SOURCES: Several electronic databases from inception to 29 February 2016. STUDY SELECTION: 21 prospective cohort, cross-sectional, and case-control studies including participants with joint inflammation and no previous definitive gout diagnosis who had MSU analysis of joint aspirate. DATA EXTRACTION: Data extraction and risk-of-bias assessment by 2 reviewers independently; overall strength of evidence (SOE) judgment by group. DATA SYNTHESIS: Recently developed algorithms including clinical, laboratory, and imaging criteria demonstrated good sensitivity (up to 88%) and fair to good specificity (up to 96%) for diagnosing gout (moderate SOE). Three studies of dual-energy computed tomography (DECT) showed sensitivities of 85% to 100% and specificities of 83% to 92% for diagnosing gout (low SOE). Six studies of ultrasonography showed sensitivities of 37% to 100% and specificities of 68% to 97%, depending on the ultrasonography signs assessed (pooled sensitivity and specificity for the double contour sign: 74% [95% CI, 52% to 88%] and 88% [CI, 68% to 96%], respectively [low SOE]). LIMITATION: Important study heterogeneity and selection bias; scant evidence in primary and urgent care settings and in patients with conditions that may be confused with or occur with gout. CONCLUSION: Multidimensional algorithms, which must be validated in primary and urgent care settings, may help clinicians make a provisional diagnosis of gout. Although DECT and ultrasonography also show promise for gout diagnosis, accessibility to these methods may be limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (Protocol registration: https://effectivehealthcare.ahrq.gov/ehc/products/564/1937/gout-protocol-140716.pdf).

Acupuncture for the Treatment of Adults with Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis.

Acupuncture has been suggested as a treatment for posttraumatic stress disorder (PTSD), yet its clinical effects are unclear. This review aims to estimate effects of acupuncture on PTSD symptoms, depressive symptoms, anxiety symptoms, and sleep quality for adults with PTSD. We searched 10 databases in January 2016 to identify eligible randomized controlled trials (RCTs). We performed random effects meta-analyses and examined quality of the body of evidence (QoE) using the GRADE approach to rate confidence in meta-analytic effect estimates. Seven RCTs with 709 participants met inclusion criteria. We identified very low QoE indicating significant differences favoring acupuncture (versus any comparator) at post-intervention on PTSD symptoms (standardized mean difference [SMD] = -0.80, 95% confidence interval [CI] [-1.59, -0.01], 6 RCTs), and low QoE at longer follow-up on PTSD (SMD = -0.46, 95% CI [-0.85, -0.06], 4 RCTs) and depressive symptoms (SMD = -0.56; 95% CI [-0.88, -0.23], 4 RCTs). No significant differences were observed between acupuncture and comparators at post-intervention for depressive symptoms (SMD = -0.58, 95% CI [-1.18, 0.01], 6 RCTs, very low QoE), anxiety symptoms (SMD = -0.82, 95% CI [-2.16, 0.53], 4 RCTs, very low QoE), and sleep quality (SMD = -0.46, 95% CI [-3.95, 3.03], 2 RCTs, low QoE). Safety data (7 RCTs) suggest little risk of serious adverse events, though some participants experienced minor/moderate pain, superficial bleeding, and hematoma at needle insertion sites. To increase confidence in findings, sufficiently powered replication trials are needed that measure all relevant clinical outcomes and dedicate study resources to minimizing participant attrition.

A systematic review of modifiable risk factors in the progression of multiple sclerosis.

BACKGROUND: The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors. OBJECTIVE: To systematically review modifiable risk factors and exposures associated with MS progression. METHODS: We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data. We used random meta-analysis models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the quality of evidence. RESULTS: In total, 59 studies met inclusion criteria. Lower vitamin D levels were associated with higher Expanded Disability Status Scale (EDSS) scores ( r = -0.22; confidence interval (CI) = -0.32, -0.12; 11 studies; I2 = 66%), smokers had an increased risk of MS progression (hazard ratio (HR) = 1.55; CI = 1.10, 2.19; I2 = 72%; seven studies), and there was no association of MS progression with the use of epidural analgesics during childbirth delivery (three studies). There was insufficient evidence to draw conclusions for 11 risk factors due to conflicting results or use of different predictor and outcome measures. CONCLUSION: MS progression was consistently associated with low vitamin D levels, and smoking was associated with a more rapid decline in MS disability. Studies used a variety of methods, predictors, and outcomes making it difficult to draw conclusions. Future studies should focus on prospective assessments.

A systematic review of the effects of modifiable risk factor interventions on the progression of multiple sclerosis.

BACKGROUND: Several risk factors are associated with multiple sclerosis (MS) progression and may be amenable to intervention. OBJECTIVE: To systematically review the evidence for interventions targeting risk factors for MS progression. METHODS: We searched six databases and existing reviews till March 2015 and consulted with experts to identify randomized controlled trials (RCTs) of interventions targeting MS risk factors (PROSPERO 2015:CRD42015016461). RESULTS: In total, 37 RCTs met inclusion criteria. Expanded Disability Status Scale (EDSS) scores after exercise interventions did not differ compared with untreated controls (standardized mean differences (SMDs): 0.02; confidence interval (CI): -0.40, 0.44; I2: 0%; seven RCTs; very low quality of evidence (QoE)). Dietary interventions did not show a statistically significant effect on the relative risk (RR) of progression (RR: 0.86; CI: 0.67, 1.05; I2: 0%; four RCTs; moderate QoE) compared to placebo. EDSS scores after vitamin D supplementation were not significantly different from placebo (SMD: -0.15; CI: -0.33, 0.02; I2: 0%; five RCTs; very low QoE). CONCLUSION: We did not identify any risk factor interventions with significant effects on MS progression, but the overall QoE was limited. More adequately powered trials are needed on vitamin D supplementation, long-term exercise, and smoking cessation.

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis.

BACKGROUND: Chronic pain patients increasingly seek treatment through mindfulness meditation. PURPOSE: This study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults. METHOD: We conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use. RESULTS: Thirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life. CONCLUSIONS: While mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis.

CONTEXT: Probiotics are live microorganisms intended to confer a health benefit when consumed. One condition for which probiotics have been advocated is the diarrhea that is a common adverse effect of antibiotic use. OBJECTIVE: To evaluate the evidence for probiotic use in the prevention and treatment of antibiotic-associated diarrhea (AAD). DATA SOURCES: Twelve electronic databases were searched (DARE, Cochrane Library of Systematic Reviews, CENTRAL, PubMed, EMBASE, CINAHL, AMED, MANTIS, TOXLINE, ToxFILE, NTIS, and AGRICOLA) and references of included studies and reviews were screened from database inception to February 2012, without language restriction. STUDY SELECTION: Two independent reviewers identified parallel randomized controlled trials (RCTs) of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus) for the prevention or treatment of AAD. DATA EXTRACTION: Two independent reviewers extracted the data and assessed trial quality. RESULTS: A total of 82 RCTs met inclusion criteria. The majority used Lactobacillus-based interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects meta-analysis of 63 RCTs, which included 11 811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P < .001; I(2), 54%; [risk difference, -0.07; 95% CI, -0.10 to -0.05], [number needed to treat, 13; 95% CI, 10.3 to 19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation. CONCLUSIONS: The pooled evidence suggests that probiotics are associated with a reduction in AAD. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics.

Meta-analysis: effect of interactive communication between collaborating primary care physicians and specialists.

BACKGROUND: Whether collaborative care models that enable interactive communication (timely, 2-way exchange of pertinent clinical information directly between primary care and specialist physicians) improve patient outcomes is uncertain. PURPOSE: To assess the effects of interactive communication between collaborating primary care physicians and key specialists on outcomes for patients receiving ambulatory care. DATA SOURCES: PubMed, PsycInfo, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Web of Science through June 2008 and secondary references, with no language restriction. STUDY SELECTION: Studies that evaluated the effects of interactive communication between collaborating primary care physicians and specialists on outcomes for patients with diabetes, psychiatric conditions, or cancer. DATA EXTRACTION: Contextual, intervention, and outcome data from 23 studies were extracted by one reviewer and checked by another. Study quality was assessed with a 13-item checklist. Disagreement was resolved by consensus. Main outcomes for analysis were selected by reviewers who were blinded to study results. DATA SYNTHESIS: Meta-analysis indicated consistent effects across 11 randomized mental health studies (pooled effect size, -0.41 [95% CI, -0.73 to -0.10]), 7 nonrandomized mental health studies (pooled effect size, -0.47 [CI, -0.84 to -0.09]), and 5 nonrandomized diabetes studies (pooled effect size, -0.64 [CI, -0.93 to -0.34]). These findings remained robust to sensitivity analyses. Meta-regression indicated studies that included interventions to enhance the quality of information exchange had larger effects on patient outcomes than those that did not (-0.84 vs. -0.27; P = 0.002). LIMITATIONS: Because collaborative interventions were inherently multifaceted, the efficacy of interactive communication by itself cannot be established. Inclusion of study designs with lower internal validity increased risk for bias. No studies involved oncologists. CONCLUSION: Consistent and clinically important effects suggest a potential role of interactive communication for improving the effectiveness of primary care-specialist collaboration. PRIMARY FUNDING SOURCE: RAND Health's Comprehensive Assessment of Reform Options Initiative, the Veterans Affairs Center for the Study of Provider Behavior, The Commonwealth Fund, and the Health Foundation.