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)

Early Identification of Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and Consideration for Organ Donation

Background: In patients with out-of-hospital cardiac arrest (OHCA), care requirements can conflict with the need to promptly focus efforts on organ donation in patients who are pronounced dead. Objective: To evaluate objective criteria for identifying patients with OHCA with no chance of survival during the first minutes of cardiopulmonary resuscitation to enable prompt orientation toward organ donation. Design: Retrospective assessment using OHCA data from 2 registries and 1 trial. Setting: France (Paris Sudden Death Expertise Center [SDEC] prospective cohort [2011 to 2014] and PRESENCE multicenter cluster randomized trial [ClinicalTrials.gov: NCT01009606] [2009 to 2011]) and the United States (King County, Washington, prospective cohort [2006 to 2011]). Patients: 1771 patients from the Paris SDEC 1-year cohort (2011 to 2012) and 5192 from the validation cohorts. Measurements: Evaluation of 3 objective criteria (OHCA not witnessed by emergency medical services personnel, nonshockable initial cardiac rhythm, and no return of spontaneous circulation before receipt of a third 1-mg dose of epinephrine), survival rate at hospital discharge among patients meeting these criteria, performance of the criteria, and number of patients eligible for organ donation. Results: In the Paris SDEC 1-year cohort, the survival rate among the 772 patients with OHCA who met the objective criteria was 0% (95% CI, 0.0% to 0.5%), with a specificity of 100% (CI, 97% to 100%) and a positive predictive value of 100% (CI, 99% to 100%). These results were verified in the validation cohorts. Ninety-five (12%) patients in the Paris SDEC 1-year cohort may have been eligible for organ donation. Limitation: Several patients had unknown outcomes. Conclusion: Three objective criteria enable the early identification of patients with OHCA with essentially no chance of survival and may help in decision making about the organ donation process. Primary Funding Source: French Ministry of Health.

Going Slow May Not Be Best When Quitting Smoking

Cognitive Behavioral Therapy for Chronic Insomnia: Confronting the Challenges to Implementation

Progress in the Fight Against Multidrug-Resistant Bacteria? A Review of U.S. Food and Drug Administration–Approved Antibiotics, 2010–2015

A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane–tazobactam, and ceftazidime–avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost. Data sources were FDA approval packages and databases (January 2010 to December 2015); the Red Book (Truven Health Analytics); Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (FDA); and supplementary information from company filings, press releases, and media reports. Four antibiotics were approved for acute bacterial skin and skin-structure infection. Seven had similar mechanisms of action to those of previously approved drugs. Six were initially developed by small to midsized companies, and 7 are currently marketed by 1 of 3 large companies. The drugs spent a median of 6.2 years in clinical trials (interquartile range [IQR], 5.4 to 8.8 years) and 8 months in FDA review (IQR, 7.5 to 8 months). The median number of patients enrolled in the pivotal trials was 666 (IQR, 553 to 739 patients; full range, 44 to 1005 patients), and median trial duration was 18 months (IQR, 15 to 22 months). Seven drugs were approved on the basis of pivotal trials evaluating noninferiority. One drug demonstrated superiority on an exploratory secondary end point, 2 showed decreased efficacy in patients with renal insufficiency, and 1 showed increased mortality compared with older drugs. Seven of the drugs are substantially more expensive than their trial comparators. Limitations are that future research may show benefit to patients, new drugs from older classes may show superior effectiveness in specific patient populations, and initial U.S. prices for each new antibiotic were obtained from public sources. Recently marketed antibiotics are more expensive but have been approved without evidence of clinical superiority.

The Deceptive Appeal of Direct-to-Consumer Genetics

Update in Nephrology and Hypertension: Evidence Published in 2015

Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study: Annals of Internal Medicine: Vol 166, No 1

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.

Update in Hospital Medicine: Evidence Published in 2015

Update in Rheumatology: Evidence Published in 2015