Annals of Internal Medicine Current Issue

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs

Kandathil AJ, Breitwieser FP, Sachithanandham J, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Background:

Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings.

Objective:

To explore the plasma virome of persons who inject drugs and to characterize the sensitivity and accuracy of NGMS compared with quantitative clinical standards.

Design:

Longitudinal and cross-sectional studies.

Setting:

A clinical trial (ClinicalTrials.gov: NCT01285050) and a well-characterized cohort study of persons who have injected drugs.

Participants:

Persons co-infected with hepatitis C virus (HCV) and HIV.

Measurements:

Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR).

Results:

Next-generation metagenomic sequencing generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained more than 10 000 copies/mL or IU/mL, respectively, as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1), was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Through use of a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs. In these persons, HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses, such as HCV RNA and SEN virus D.

Limitation:

The medical importance of HHpgV-1 infection is unknown.

Conclusion:

Although NGMS is insensitive for detection of viruses with relatively low plasma nucleic acid concentrations, it may have broad potential for discovery of new viral infections of possible medical importance, such as HHpgV-1.

Primary Funding Source:

National Institutes of Health.

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

Piccolo R, Gargiulo G, Franzone A, et al. — Tue, 04 Jul 2017 00:00:00 GMT

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.

Triple Therapy Versus Biologic Therapy for Active Rheumatoid Arthritis A Cost-Effectiveness Analysis

Bansback N, Phibbs CS, Sun H, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Background:

The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept–methotrexate in patients with active rheumatoid arthritis (RA).

Objective:

To determine the cost-effectiveness of etanercept–methotrexate versus triple therapy as a first-line strategy.

Design:

A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model.

Data Sources:

The RACAT trial and sources from the literature.

Target Population:

Patients with active RA despite at least 12 weeks of methotrexate therapy.

Time Horizon:

24 weeks and lifetime.

Perspective:

Societal and Medicare.

Intervention:

Etanercept–methotrexate first versus triple therapy first.

Outcome Measures:

Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).

Results of Base-Case Analysis:

The within-trial analysis found that etanercept–methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept–methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept–methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient.

Results of Sensitivity Analysis:

Considering a long-term perspective, an initial strategy of etanercept–methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions.

Limitation:

Data on the long-term benefit of triple therapy are uncertain.

Conclusion:

Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit.

Primary Funding Source:

The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health–American Recovery and Reinvestment Act.

Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms A Systematic Review

Malhotra A, Wu X, Forman HP, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Background:

Small unruptured intracranial aneurysms (UIAs) are increasingly diagnosed. Management depends on growth and rupture risks, which may vary by aneurysm size.

Purpose:

To summarize evidence about the growth and rupture risk of UIAs 7 mm and smaller and to explore differences in growth and rupture risks of very small (≤3 mm) and small (≤5 mm) aneurysms.

Data Sources:

MEDLINE, EMBASE, Scopus, and the Cochrane Library from inception to 2017 (with no language restrictions).

Study Selection:

Published case series and observational studies that reported natural history data on UIAs 7 mm and smaller.

Data Extraction:

2 reviewers abstracted study information, evaluated study quality, and graded strength of evidence.

Data Synthesis:

Of 26 studies, 5, 10, and 8 described the growth rate of aneurysms 3 mm and smaller, 5 mm and smaller, and 7 mm and smaller, respectively, whereas rupture rates were reported in 7, 11, and 13 studies for aneurysms 3 mm and smaller, 5 mm and smaller, and 7 mm and smaller, respectively. The annualized growth rate was less than 3% in all but 1 study for all 3 size categories. The annualized rupture rate was 0%, less than 0.5%, and less than 1% for the 3 size categories, respectively. Strength of evidence was very low quality for growth rates and low quality for rupture rates.

Limitation:

Heterogeneous definitions of growth; heterogeneous and selective treatment and follow-up methods, particularly in high-risk patients.

Conclusion:

Poor-quality evidence suggests that small UIAs have low growth and rupture rates and very small UIAs have little or no risk for rupture.

Primary Funding Source:

None.

Methods and Reporting Studies Assessing Fecal Microbiota Transplantation A Systematic Review

Bafeta A, Yavchitz A, Riveros C, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Background:

Fecal microbiota transplantation (FMT) could be a novel treatment option for several chronic diseases associated with altered gut microbiota.

Purpose:

To examine the conduct and reporting of studies assessing FMT.

Data Sources:

Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science from inception to 31 January 2017.

Study Selection:

Two reviewers independently examined titles and abstracts to identify all English-language reports of human clinical studies assessing the safety or efficacy of FMT.

Data Extraction:

Three reviewers independently assessed study types and characteristics and the reporting of important methodological components of the FMT intervention.

Data Synthesis:

Most (84%) of the 85 published reports found addressed the use of FMTs for Clostridium difficile infection or inflammatory bowel disease, and most (87%) were non–randomized controlled trials. Important methodological components that were not reported in published studies included the following: eligibility criteria for donors (47%), materials used for collecting stools and the period of collection (96%), methods used for conservation of stools (76%), the amount and type of stools used (for example, fresh or frozen), and duration of stool conservation (67%). Many (58%) did not report an analysis of microbiota composition.

Limitations:

Lack of universal consensus regarding the most important methodological components of FMT and inability to assess the actual conduct of studies and whether the publication process affected the completeness of reporting.

Conclusion:

Key components of FMT interventions, which are necessary to replicate and understand study findings about efficacy and safety, are poorly reported.

Primary Funding Source:

No specific funding.

CONSORT Statement for Randomized Trials of Nonpharmacologic Treatments: A 2017 Update and a CONSORT Extension for Nonpharmacologic Trial Abstracts

Boutron I, Altman DG, Moher D, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists.Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports.

Toward Patient-Centered Hospital Design: What Can Airports Teach Us?

Mullangi S, Ibrahim AM, Chopra V. — Tue, 04 Jul 2017 00:00:00 GMT

Hospitals are still behind when it comes to implementing patient-friendly processes to improve the access and layout of hospital services. Could hospitals learn from airports in meeting the needs of patients?

New Department of Veterans Affairs and Department of Defense Guidelines on Pain Management With Opioids: Comment and Concern

McLellan A. — Tue, 04 Jul 2017 00:00:00 GMT

The Department of Veterans Affairs/Department of Defense recently revised guidelines on prescribing opioids for the management of chronic noncancer pain. This commentary discusses the guidelines and why they are a welcome and timely update.

Understanding Veteran Wait Times

Shulkin D. — Tue, 04 Jul 2017 00:00:00 GMT

The newly appointed secretary of the U.S. Department of Veterans Affairs (VA) describes the response to the access crisis and his vision for the VA that is based on how veterans want to receive care.

Improvement at Any Cost? The Art and Science of Choosing Treatment Strategies for Rheumatoid Arthritis

Losina E, Katz JN. — Tue, 04 Jul 2017 00:00:00 GMT

Bansback and colleagues reported a cost-effectiveness analysis of triple therapy with conventional disease-modifying antirheumatic drugs compared with etanercept and methotrexate. The editorialists discuss the findings.

The Past, Present, and Future of Dual-Antiplatelet Therapy Duration in Percutaneous Coronary Intervention

Abbott J. — Tue, 04 Jul 2017 00:00:00 GMT

The editorialist discusses the findings of Piccolo and colleagues' study as well as strategies to individualize decision making about DAPT duration.

Small Cerebral Aneurysms: Can We Identify Patients at Risk for Rupture?

Starke RM. — Tue, 04 Jul 2017 00:00:00 GMT

Malhotra and colleagues' review examined the risk for growth and rupture of small unruptured intracranial aneurysms. The editorialist discusses the importance of the clinical question the review attempts to answer but believes that the poor quality of the available evidence makes the answer elusive.

Treatment With Fecal Microbiota Transplantation: The Need for Complete Methodological Reporting for Clinical Trials

Young VB. — Tue, 04 Jul 2017 00:00:00 GMT

The editorialist discusses Bafeta and colleagues' systematic review, which examined the methods described in 85 studies of fecal microbiota transplantation.

Data Sharing Statements for Clinical Trials: A Requirement of the International Committee of Medical Journal Editors

Taichman DB, Sahni P, Pinborg A, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Participants in clinical trials often place themselves at risk to help the medical community learn how to improve care. To make the most of these efforts, the editors of 13 major medical journals have adopted new criteria on sharing data from clinical trials.

A Letter to New Interns

Taichman DB, Moyer DV, Laine C. — Tue, 04 Jul 2017 00:00:00 GMT

This issue includes 2 Annals Graphic Medicine pieces about the beginning of internship. This editorial discusses what residents face during this time.

Incidental Findings in Research Studies: One Student's Experience

Canady FJ. — Tue, 04 Jul 2017 00:00:00 GMT

Postmalaria Neurologic Syndrome—Autoimmune Encephalitis With Anti–Voltage-Gated Potassium-Channel Antibodies

Sahuguet J, Poulet A, Bou Ali H, et al. — Tue, 04 Jul 2017 00:00:00 GMT

Do Sugar-Sweetened Beverages Cause Obesity and Diabetes?

Slavin J. — Tue, 04 Jul 2017 00:00:00 GMT

Do Sugar-Sweetened Beverages Cause Obesity and Diabetes?

Jack MM. — Tue, 04 Jul 2017 00:00:00 GMT

Do Sugar-Sweetened Beverages Cause Obesity and Diabetes?

Schillinger D, Kearns C. — Tue, 04 Jul 2017 00:00:00 GMT

Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus

Inzucchi SE, Kosiborod M. — Tue, 04 Jul 2017 00:00:00 GMT

Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus

Bell DH. — Tue, 04 Jul 2017 00:00:00 GMT

Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus

Barry MJ, Humphrey LL, Qaseem A. — Tue, 04 Jul 2017 00:00:00 GMT

Counterclockwise

Masson V. — Tue, 04 Jul 2017 00:00:00 GMT

Intensive Care

Butka B. — Tue, 04 Jul 2017 00:00:00 GMT

Abandon All

Cohen S. — Tue, 04 Jul 2017 00:00:00 GMT

Annals for Educators - 4 July 2017

Taichman DB. — Tue, 04 Jul 2017 00:00:00 GMT

Management of Newly Diagnosed HIV Infection

Feinberg J, Keeshin S. — Tue, 04 Jul 2017 00:00:00 GMT

No field in medicine has moved as swiftly as HIV/AIDS over the past 35 years. Because of the rapid turnover of key information, this In the Clinic focuses on essential principles of care for newly diagnosed adults with HIV-1 infection and how to prevent infection in persons at risk. To ensure continued usefulness, future directions in therapy and how to access updated information on a continuous basis are emphasized.

Annals Graphic Medicine - July Plunge

Natter M. — Tue, 04 Jul 2017 00:00:00 GMT

Annals Graphic Medicine - Internship

Bitterman J. — Tue, 04 Jul 2017 00:00:00 GMT