World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of Physicians

Utility, Appropriateness, and Content of Electronic Consultations Across Medical Subspecialties: A Cohort Study: Annals of Internal Medicine: Vol 172, No 10

Background: Electronic consultations (e-consults) can facilitate patient access to specialists, minimize travel, and reduce unnecessary in-person visits. However, metrics to enable study of e-consults and their effect on processes and patient care are lacking. Objective: To assess novel metrics of e-consult appropriateness and utility. Design: Retrospective cohort study. Setting: Primary and specialty care practices at 2 large academic and 2 community hospitals of an integrated health system. Participants: Patients with e-consult requests to 5 specialties—hematology, infectious disease, dermatology, rheumatology, and psychiatry—between October 2017 and November 2018. Measurements: The appropriateness of e-consult inquiries was assessed by review of medical records and defined as meeting the following 4 criteria: not answerable by reviewing evidence-based summary sources (“point-of-care resource test”), not merely requesting logistic information, having appropriate clinical urgency, and having appropriate patient complexity. Interrater agreement in assessments of e-consult appropriateness was assessed by the κ statistic. Utility of e-consults was assessed by the rate of avoided visits (AVs), defined by the absence of an in-person visit to the same specialty within 120 days. Results: Overall, 6512 eligible e-consults were made by 1096 referring providers to 121 specialist consultants. Inquiries were characterized as diagnostic, therapeutic, for provider education, or at the request of the patient. Most consultations were answered within 1 day, with variation across specialties (73.1% for psychiatry to 87.8% for infectious disease). Overall, 70.2% of e-consults met all 4 criteria for appropriateness; the frequency of unmet criteria varied among specialties. Raters agreed on the appropriateness of 94% of e-consults (κ = 0.57 [95% CI, 0.36 to 0.79]), indicating moderate agreement. The overall rate of AVs across the 5 specialties was 81.2%; the highest rate was in psychiatry (92.6%) and the lowest in dermatology (61.9%). Limitation: Generalizability is unknown outside a single integrated health system, where requesting and consulting providers share a common electronic health record. Conclusion: Novel metrics to assess the appropriateness and utility of e-consults provide meaningful insight into practice, provide a rubric for comparison in future studies in additional settings, and suggest areas to improve resource use and patient care. Primary Funding Source: None.

Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication: A Double-Blind, Randomized, Controlled Trial: Annals of Internal Medicine: Vol 172, No 12

Background: Although consensus supports eradication of Helicobacter pylori infections, antimicrobial resistance has substantially reduced eradication rates with most current therapies. Objective: To assess the effectiveness of a novel rifabutin-based therapy (RHB-105) for H pylori eradication. Design: Phase 3, double-blind trial (ERADICATE Hp2). (ClinicalTrials.gov: NCT03198507) Setting: 55 clinical research sites in the United States. Participants: 455 treatment-naive adults with epigastric discomfort and confirmed H pylori infection. Intervention: RHB-105 (amoxicillin, 3 g; omeprazole, 120 mg; and rifabutin, 150 mg) versus active comparator (amoxicillin, 3 g, and omeprazole, 120 mg), given as 4 capsules every 8 hours for 14 days. Measurements: Between-group difference for H pylori eradication rate, demonstrated by 13C urea breath test 4 weeks after treatment, analyzed by using the χ2 test. Results: In the intention-to-treat population, the eradication rate was higher with RHB-105 than with the active comparator (228 vs. 227 patients, respectively; 83.8% [95% CI, 78.4% to 88.0%] vs. 57.7% [95% CI, 51.2% to 64.0%]; P < 0.001). Eradication rates were unaffected by resistance to clarithromycin or metronidazole. No rifabutin resistance was detected. The most commonly reported adverse events (incidence ≥5%) were diarrhea (10.1% with RHB-105 vs. 7.9% with active comparator), headache (7.5% vs. 7.0%), and nausea (4.8% vs. 5.3%). Limitation: Persons of Asian descent were excluded because of their higher prevalence of poor cytochrome P450 2C19 metabolizers. Conclusion: These findings suggest potential for RHB-105 as first-line empirical H pylori therapy, addressing an unmet need in the current environment of increasing antibiotic resistance. Primary Funding Source: RedHill Biopharma Ltd.

Annals Clinical Decision Making: Avoiding Cognitive Errors in Clinical Decision Making

Comparative Pricing of Branded Tenofovir Alafenamide–Emtricitabine Relative to Generic Tenofovir Disoproxil Fumarate–Emtricitabine for HIV Preexposure Prophylaxis: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 172, No 9

Background: Tenofovir alafenamide–emtricitabine (F/TAF) was recently approved as a noninferior and potentially safer option than tenofovir disoproxil fumarate–emtricitabine (F/TDF) for HIV preexposure prophylaxis (PrEP) in the United States. Objective: To estimate the greatest possible clinical benefits and economic savings attributable to the improved safety profile of F/TAF and the maximum price payers should be willing to pay for F/TAF over generic F/TDF. Design: Cost-effectiveness analysis. Data Sources: Published literature on F/TDF safety (in persons with and those without HIV) and the cost and quality-of-life effects of fractures and end-stage renal disease (ESRD). Target Population: Age-stratified U.S. men who have sex with men (MSM) using PrEP. Time Horizon: Five years. Perspective: Health care sector. Intervention: Preexposure prophylaxis with F/TAF versus F/TDF. Outcome Measures: Fractures averted, cases of ESRD averted, quality-adjusted life-years (QALYs) saved, costs, incremental cost-effectiveness ratios (ICERs), and maximum justifiable price for F/TAF compared with generic F/TDF. Results of Base-Case Analysis: Over a 5-year horizon, compared with F/TDF, F/TAF averted 2101 fractures and 25 cases of ESRD for the 123 610 MSM receiving PrEP, with an ICER of more than $7 million per QALY. At a 50% discount for generic F/TDF ($8300 per year) and a societal willingness to pay up to $100 000 per QALY, the maximum fair price for F/TAF was $8670 per year. Results of Sensitivity Analysis: Among persons older than 55 years, the ICER for F/TAF remained more than $3 million per QALY and the maximum permissible fair price for F/TAF was $8970 per year. Results were robust to alternative time horizons and PrEP-using population sizes. Limitation: Intermittent use and on-demand PrEP were not considered. Conclusion: In the presence of a generic F/TDF alternative, the improved safety of F/TAF is worth no more than an additional $370 per person per year. Primary Funding Source: National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, National Institute of Mental Health, and Massachusetts General Hospital Executive Committee on Research.

Uses and Limitations of the Restricted Mean Survival Time: Illustrative Examples From Cardiovascular Outcomes and Mortality Trials in Type 2 Diabetes

The restricted mean survival time (RMST) has been advocated as an alternative or a supplement to the hazard ratio for reporting the effect of an intervention in a randomized clinical trial. The RMST difference allows quantification of the postponement of an outcome during a specified (restricted) interval and corresponds to the difference between the areas under the 2 survival curves for the intervention and control groups. This article presents examples of the use of the RMST in a research and a clinical context. First, the authors demonstrate how the RMST difference can answer research questions about the efficacy of different treatments. Estimates are presented for the effects of pharmacologic or strategy-driven glucose-lowering interventions for adults with type 2 diabetes from 36 trials and 9 follow-up studies reporting cardiovascular outcomes and mortality. The authors show how these measures may be used to mitigate uncertainty about the efficacy of intensive glucose control. Second, the authors demonstrate how the RMST difference may be used in the setting of a clinical consultation to guide the decision to start or discontinue a treatment. They then discuss the advantages of the RMST over the absolute risk difference, the number needed to treat, and the median survival time difference. They argue that the RMST difference is both easy to interpret and flexible in its application to different settings. Finally, they highlight the major limitations of the RMST, including difficulties in comparing studies of heterogeneous designs and in inferring the long-term effects of treatments using trials of short duration, and summarize the available statistical software for calculating the RMST.

Achieving Health Equity in Preventive Services: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Background: Disadvantaged populations in the United States experience disparities in the use of preventive health services. Purpose: To examine effects of barriers that create health disparities in 10 recommended preventive services for adults, and to evaluate the effectiveness of interventions to reduce them. Data Sources: English-language searches of Ovid MEDLINE, PsycINFO, SocINDEX, and the Veterans Affairs Health Services database (1 January 1996 to 5 July 2019); reference lists. Study Selection: Trials, observational studies with comparison groups, and systematic reviews of populations adversely affected by disparities that reported effects of barriers on use of any of the 10 selected preventive services or that reported the effectiveness of interventions to reduce disparities in use of a preventive service by improving intermediate or clinical outcomes. Data Extraction: Dual extraction and assessment of study quality, strength of evidence, and evidence applicability. Data Synthesis: No studies reported effects of provider-specific barriers on preventive service use. Eighteen studies reporting effects of patient barriers, such as insurance coverage or lack of a regular provider, on preventive service use had mixed and inconclusive findings. Studies of patient–provider interventions (n = 12), health information technologies (n = 11), and health system interventions (n = 88) indicated higher cancer screening rates with patient navigation; telephone calls, prompts, and other outreach methods; reminders involving lay health workers; patient education; risk assessment, counseling, and decision aids; screening checklists; community engagement; and provider training. Single studies showed that clinician-delivered and technology-assisted interventions improved rates of smoking cessation and weight loss, respectively. Limitation: Insufficient or low strength of evidence and applicability for most interventions except patient navigation, telephone calls and prompts, and reminders involving lay health workers. Conclusion: In populations adversely affected by disparities, patient navigation, telephone calls and prompts, and reminders involving lay health workers increase cancer screening. Primary Funding Source: National Institutes of Health Office of Disease Prevention through an interagency agreement with the Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109263)

National Institutes of Health Pathways to Prevention Workshop: Achieving Health Equity in Preventive Services

Expert groups, including the U.S. Preventive Services Task Force (USPSTF), recommend a range of clinical preventive services for persons at average risk for disease. Use of these services often is substantially lower among racial and ethnic minority groups, rural residents, and persons of lower socioeconomic status. On 19 and 20 June 2019, the National Institutes of Health (NIH) convened the Pathways to Prevention Workshop: Achieving Health Equity in Preventive Services to assess the available evidence on disparities in the use of 10 USPSTF-recommended clinical preventive services for cancer, heart disease, and diabetes. The workshop was cosponsored by the NIH Office of Disease Prevention; National Institute on Minority Health and Health Disparities; National Cancer Institute; National Heart, Lung, and Blood Institute; and National Institute of Diabetes and Digestive and Kidney Diseases. A multidisciplinary working group developed the agenda, and an Evidence-based Practice Center prepared the evidence report. During the workshop, invited experts considered the evidence, with discussion among attendees. After weighing evidence from the review, presentations, and public comments, an independent panel prepared a draft report that was posted for public comment. This final report summarizes the panel's findings, identifying current gaps in knowledge. The panel made 26 recommendations for new research and methods development to improve implementation of proven services to reduce disparities in preventable conditions.

Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis: Annals of Internal Medicine: Vol 172, No 6

Background: Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations. Purpose: To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD. Data Sources: English-language searches of several bibliographic sources from database inception to 2 January 2019. Study Selection: 68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, “usual care,” or other pharmacologic interventions. Data Extraction: Two reviewers independently extracted data and rated study quality and strength of evidence (SOE). Data Synthesis: Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function. Limitation: Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs. Conclusion: Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609)

The Impact of a Sweetened Beverage Tax on Beverage Volume Sold in Cook County, Illinois, and Its Border Area

Background: Sugar-sweetened beverage (SSB) consumption is linked to adverse health outcomes. Objective: To evaluate the impact of the 2017 Cook County, Illinois, Sweetened Beverage Tax (SBT) on the volume of taxed and untaxed beverages sold in Cook County and its 2-mile border area. Design: Pre–post intervention–comparison site difference-in-differences study. Setting: Cook County, Illinois, and St. Louis City and County, Missouri, 2016 to 2017. Participants: Universal product code–level store scanner data from supermarkets and grocery, convenience, drug, mass merchandise, and dollar stores. Measurements: Beverage volume sold of taxed and untaxed beverages, across product categories and sizes. Results: Volume sold of taxed beverages decreased by 27% (ratio of incidence rate ratios [RIRR], 0.73 [95% CI, 0.70 to 0.75]) on average in Cook County relative to St. Louis during the 4 months that the SBT was in effect (compared with the same 4-month pretax period), with a net decrease of 21% after increases in volume sold in its border area (cross-border shopping) were taken into account. The magnitude of the decrease in volume sold across types of taxed beverages was heterogeneous: −32% (RIRR, 0.68 [CI, 0.65 to 0.72]) for soda versus −11% (RIRR, 0.89 [CI, 0.82 to 0.97]) for energy drinks, −37% (RIRR, 0.63 [CI, 0.59 to 0.66]) for artificially sweetened beverages versus −25% (RIRR, 0.75 [CI, 0.72 to 0.79]) for SSBs, and −29% (RIRR, 0.71 [CI, 0.68 to 0.74]) for family-size versus −19% (RIRR, 0.81 [CI, 0.79 to 0.84]) for individual-size beverages. There was no significant change in volume sold of untaxed beverages in Cook County or its border area. Limitation: Data source did not allow for evaluation by store type or distance of outlets from the border. Conclusion: The Cook County SBT led to a substantial reduction in the volume sold of taxed beverages in Cook County. Part of this effect was offset by cross-border shopping. Cross-border shopping was limited to tax avoidance and did not extend to untaxed beverages. Primary Funding Source: Bloomberg Philanthropies.