The Long and Winding Road to Clinical Guidelines on the Diagnosis and Management of Gout

To Treat or Not to Treat (to Target) in Gout

Do Patient-Centered Medical Homes Enhance Patients' Medication Adherence? Findings on the Next Frontier in Quality Improvement

Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial: Annals of Internal Medicine: Vol 166, No 8

Background: Interleukin-1 (IL-1), an important proinflammatory cytokine, is suspected to play a role in chronic fatigue syndrome (CFS). Objective: To evaluate the effect of subcutaneous anakinra versus placebo on fatigue severity in female patients with CFS. Design: Randomized, placebo-controlled trial from July 2014 to May 2016. Patients, providers, and researchers were blinded to treatment assignment. (ClinicalTrials.gov: NCT02108210) Setting: University hospital in the Netherlands. Patients: 50 women aged 18 to 59 years with CFS and severe fatigue leading to functional impairment. Intervention: Participants were randomly assigned to daily subcutaneous anakinra, 100 mg (n = 25), or placebo (n = 25) for 4 weeks and were followed for an additional 20 weeks after treatment (n = 50). Measurements: The primary outcome was fatigue severity, measured by the Checklist Individual Strength subscale (CIS-fatigue) at 4 weeks. Secondary outcomes were level of impairment, physical and social functioning, psychological distress, and pain severity at 4 and 24 weeks. Results: At 4 weeks, 8% (2 of 25) of anakinra recipients and 20% (5 of 25) of placebo recipients reached a fatigue level within the range reported by healthy persons. There were no clinically important or statistically significant differences between groups in CIS-fatigue score at 4 weeks (mean difference, 1.5 points [95% CI, −4.1 to 7.2 points]) or the end of follow-up. No statistically significant between-group differences were seen for any secondary outcome at 4 weeks or the end of follow-up. One patient in the anakinra group discontinued treatment because of an adverse event. Patients in the anakinra group had more injection site reactions (68% [17 of 25] vs. 4% [1 of 25]). Limitation: Small sample size and wide variability in symptom duration; inclusion was not limited to patients with postinfectious symptoms. Conclusion: Peripheral IL-1 inhibition using anakinra for 4 weeks does not result in a clinically significant reduction in fatigue severity in women with CFS and severe fatigue. Primary Funding Source: Interleukin Foundation and an independent donor who wishes to remain anonymous.

Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention

Background: The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention (PCI). Objective: To evaluate the safety and efficacy of DAPT duration according to DAPT score. Design: Retrospective assessment of DAPT score–guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286) Setting: PCI patients. Patients: 1970 patients undergoing PCI. Intervention: DAPT (aspirin and clopidogrel) for 24 versus 6 months. Measurements: Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months. Results: 884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference [RD] for score ≥2, −2.05 percentage points [95% CI, −5.04 to 0.95 percentage points]; RD for score <2, 2.91 percentage points [CI, −0.43 to 6.25 percentage points]; P = 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, −7.55 percentage points [CI, −12.85 to −2.25 percentage points]). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point [CI, −1.20 to 1.60 percentage points]; RD for score <2, 2.58 percentage points [CI, 0.71 to 4.46 percentage points]; P = 0.046). Limitation: Retrospective calculation of the DAPT score. Conclusion: Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study. Primary Funding Source: None.

Missed Opportunities for Measles, Mumps, Rubella Vaccination Among Departing U.S. Adult Travelers Receiving Pretravel Health Consultations

Background: Measles outbreaks continue to occur in the United States and are mostly due to infections in returning travelers. Objective: To describe how providers assessed the measles immunity status of departing U.S. adult travelers seeking pretravel consultation and to assess reasons given for nonvaccination among those considered eligible to receive the measles, mumps, rubella (MMR) vaccine. Design: Observational study in U.S. pretravel clinics. Setting: 24 sites associated with Global TravEpiNet (GTEN), a Centers for Disease Control and Prevention–funded consortium. Patients: Adults (born in or after 1957) attending pretravel consultations at GTEN sites (2009 to 2014). Measurements: Structured questionnaire completed by traveler and provider during pretravel consultation. Results: 40 810 adult travelers were included; providers considered 6612 (16%) to be eligible for MMR vaccine at the time of pretravel consultation. Of the MMR-eligible, 3477 (53%) were not vaccinated at the visit; of these, 1689 (48%) were not vaccinated because of traveler refusal, 966 (28%) because of provider decision, and 822 (24%) because of health systems barriers. Most MMR-eligible travelers who were not vaccinated were evaluated in the South (2262 travelers [65%]) or at nonacademic centers (1777 travelers [51%]). Nonvaccination due to traveler refusal was most frequent in the South (1432 travelers [63%]) and in nonacademic centers (1178 travelers [66%]). Limitation: These estimates could underrepresent the opportunities for MMR vaccination because providers accepted verbal histories of disease and vaccination as evidence of immunity. Conclusion: Of U.S. adult travelers who presented for pretravel consultation at GTEN sites, 16% met criteria for MMR vaccination according to the provider's assessment, but fewer than half of these travelers were vaccinated. An increase in MMR vaccination of eligible U.S. adult travelers could reduce the likelihood of importation and transmission of measles virus. Primary Funding Source: Centers for Disease Control and Prevention, National Institutes of Health, and the Steve and Deborah Gorlin MGH Research Scholars Award.

Allocation of Internal Medicine Resident Time in a Swiss Hospital: A Time and Motion Study of Day and Evening Shifts

Background: Little current evidence documents how internal medicine residents spend their time at work, particularly with regard to the proportions of time spent in direct patient care versus using computers. Objective: To describe how residents allocate their time during day and evening hospital shifts. Design: Time and motion study. Setting: Internal medicine residency at a university hospital in Switzerland, May to July 2015. Participants: 36 internal medicine residents with an average of 29 months of postgraduate training. Measurements: Trained observers recorded the residents' activities using a tablet-based application. Twenty-two activities were categorized as directly related to patients, indirectly related to patients, communication, academic, nonmedical tasks, and transition. In addition, the presence of a patient or colleague and use of a computer or telephone during each activity was recorded. Results: Residents were observed for a total of 696.7 hours. Day shifts lasted 11.6 hours (1.6 hours more than scheduled). During these shifts, activities indirectly related to patients accounted for 52.4% of the time, and activities directly related to patients accounted for 28.0%. Residents spent an average of 1.7 hours with patients, 5.2 hours using computers, and 13 minutes doing both. Time spent using a computer was scattered throughout the day, with the heaviest use after 6:00 p.m. Limitation: The study involved a small sample from 1 institution. Conclusion: At this Swiss teaching hospital, internal medicine residents spent more time at work than scheduled. Activities indirectly related to patients predominated, and about half the workday was spent using a computer. Primary Funding Source: Information Technology Department and Department of Internal Medicine of Lausanne University Hospital.

Maintenance of Weight Loss After Initiation of Nutrition Training: A Randomized Trial: Annals of Internal Medicine: Vol 166, No 7

Background: Weight regain after successful weight loss interventions is common. Objective: To establish the efficacy of a weight loss maintenance program compared with usual care in obese adults. Design: 2-group, parallel, randomized trial stratified by initial weight loss (<10 kg vs. ≥10 kg), conducted from 20 August 2012 to 18 December 2015. Outcome assessors were blinded to treatment assignment. (ClinicalTrials.gov: NCT01357551) Setting: 3 primary care clinics at the Veterans Affairs Medical Center in Durham and Raleigh, North Carolina. Patients: Obese outpatients (body mass index ≥30 kg/m2) who lost 4 kg or more of body weight during a 16-week, group-based weight loss program. Intervention: The maintenance intervention, delivered primarily by telephone, addressed satisfaction with outcomes, relapse-prevention planning, self-monitoring, and social support. Usual care involved no contact except for study measurements. Measurements: Primary outcome was mean weight regain at week 56. Secondary outcomes included self-reported caloric intake, walking, and moderate physical activity. Results: Of 504 patients in the initial program, 222 lost at least 4 kg of body weight and were randomly assigned to maintenance (n = 110) or usual care (n = 112). Retention was 85%. Most patients were middle-aged white men. Mean weight loss during initiation was 7.2 kg (SD, 3.1); mean weight at randomization was 103.6 kg (SD, 20.4). Estimated mean weight regain was statistically significantly lower in the intervention (0.75 kg) than the usual care (2.36 kg) group (estimated mean difference, 1.60 kg [95% CI, 0.07 to 3.13 kg]; P = 0.040). No statistically significant differences in secondary outcomes were seen at 56 weeks. No adverse events directly attributable to the intervention were observed. Limitations: Results may not generalize to other settings or populations. Dietary intake and physical activity were self-reported. Duration was limited to 56 weeks. Conclusion: An intervention focused on maintenance-specific strategies and delivered in a resource-conserving way modestly slowed the rate of weight regain in obese adults. Primary Funding Source: Veterans Affairs Health Services Research and Development Service.

Association of Viral Suppression With Lower AIDS-Defining and Non–AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study: Annals of Internal Medicine: Vol 169, No 2

Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non–AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses. Objective: To determine whether viral suppression is associated with decreased cancer risk. Design: Prospective cohort. Setting: Department of Veterans Affairs. Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015. Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL). Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses. Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated. Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk. Primary Funding Source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Exercise as Medicine