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.

Effects of Interleukin-1β Inhibition on Incident Anemia: Exploratory Analyses From a Randomized Trial: Annals of Internal Medicine: Vol 172, No 8

Background: Inflammatory cytokines, such as interleukin (IL)-1β, alter iron homeostasis and erythropoiesis, resulting in anemia, but whether inhibition of IL-1β can reverse these effects is unclear. Objective: To determine whether IL-1β inhibition with canakinumab reduces incident anemia and improves hemoglobin levels among those with prevalent anemia. Design: Exploratory analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01327846) Setting: Many clinical sites in 39 countries. Participants: 8683 CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) participants without anemia at trial entry and 1303 with prevalent anemia at trial entry. Intervention: Random assignment to receive placebo or canakinumab (50, 150, or 300 mg) subcutaneously once every 3 months. Measurements: Primary outcome was incident anemia (hemoglobin level <130 g/L in men or <120 g/L in women). Results: Anemia incidence increased with rising baseline levels of high-sensitivity C-reactive protein (hsCRP), and both hsCRP and IL-6 decreased among participants receiving canakinumab compared with the placebo group. During a median follow-up of 3.7 years, participants without baseline anemia who received canakinumab at any dosage had significantly less incident anemia than those who received placebo (hazard ratio, 0.84 [95% CI, 0.77 to 0.93]; P < 0.001). Compared with placebo, the greatest benefits of IL-1β inhibition on incident anemia were observed among participants with the most robust anti-inflammatory response, an effect corroborated in formal mediation analyses. Among those with baseline anemia, canakinumab increased mean hemoglobin levels by 11.3 g/L (P < 0.001) compared with placebo after 2 years of treatment. Canakinumab increased the risk for infection and was associated with mild cases of thrombocytopenia and neutropenia, none of which was grade 3 or higher. Limitation: CANTOS was not designed to assess the cause of anemia in individual trial participants. Conclusion: These exploratory analyses of randomized trial data provide proof of principle that inflammation inhibition, at least through the IL-1β/IL-6 signaling pathway, reduces the incidence of anemia and improves hemoglobin levels in patients with anemia. Primary Funding Source: Novartis Pharmaceuticals.

Effect of Acupuncture for Postprandial Distress Syndrome: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 172, No 12

Background: Postprandial distress syndrome (PDS) is the most common subtype of functional dyspepsia. Acupuncture is commonly used to treat PDS, but its effect is uncertain because of the poor quality of prior studies. Objective: To assess the efficacy of acupuncture versus sham acupuncture in patients with PDS. Design: Multicenter, 2-group, randomized clinical trial. (ISRCTN registry number: ISRCTN12511434) Setting: 5 tertiary hospitals in China. Participants: Chinese patients aged 18 to 65 years meeting Rome IV criteria for PDS. Intervention: 12 sessions of acupuncture or sham acupuncture over 4 weeks. Measurements: The 2 primary outcomes were the response rate based on overall treatment effect and the elimination rate of all 3 cardinal symptoms: postprandial fullness, upper abdominal bloating, and early satiation after 4 weeks of treatment. Participants were followed until week 16. Results: Among the 278 randomly assigned participants, 228 (82%) completed outcome measurements at week 16. The estimated response rate from generalized linear mixed models at week 4 was 83.0% in the acupuncture group versus 51.6% in the sham acupuncture group (difference, 31.4 percentage points [95% CI, 20.3 to 42.5 percentage points]; P < 0.001). The estimated elimination rate of all 3 cardinal symptoms was 27.8% in the acupuncture group versus 17.3% in the sham acupuncture group (difference, 10.5 percentage points [CI, 0.08 to 20.9 percentage points]; P = 0.034). The efficacy of acupuncture was maintained during the 12-week posttreatment follow-up. There were no serious adverse events. Limitation: Lack of objective outcomes and daily measurement, high dropout rate, and inability to blind acupuncturists. Conclusion: Among patients with PDS, acupuncture resulted in increased response rate and elimination rate of all 3 cardinal symptoms compared with sham acupuncture, with sustained efficacy over 12 weeks in patients who received thrice-weekly acupuncture for 4 weeks. Primary Funding Source: Beijing Municipal Science and Technology Commission.

Sitters as a Patient Safety Strategy to Reduce Hospital Falls: A Systematic Review: Annals of Internal Medicine: Vol 172, No 5

Background: Bedside “sitters” are often used for patients at high risk for falls, but they are expensive and their effectiveness is unclear. Purpose: To review evidence about the effect of sitters and alternatives to sitters on patient falls in acute care hospitals. Data Sources: PubMed searches to 8 October 2019, other databases from inception to December 2018, citation searches on key articles, and a Google search (22 October 2019). Study Selection: English-language studies of any design that assessed the effect of adding sitters to usual care or compared alternatives to sitters (for example, video monitors or “close observation units”) for adult patients on general wards of acute care hospitals and reported falls as a primary outcome. Data Extraction: Dual-reviewer extraction of study data and risk of bias; single reviewer with group discussion for GRADE (Grading of Recommendations Assessment, Development and Evaluation) certainty of evidence. Data Synthesis: Of 20 studies meeting inclusion criteria, 2 added sitters to usual care and 18 compared alternatives to sitters. There were no randomized trials, 11 time-series studies, 1 retrospective quasi-experimental study, and 8 pre–post studies. All studies had at least 1 methodological limitation. Two studies provided very-low-certainty evidence that adding sitters reduced falls. Eight studies provided moderate-certainty evidence that interventions that included video monitoring reduced sitter use and either did not affect or reduced the number of falls. Very-low-certainty evidence suggested that interventions that included nurse assessment tools (3 studies) or a close observation unit (2 studies) were effective alternatives to sitters. Limitation: No studies had low risk of bias, publication bias is likely, and studies may have been missed. Conclusion: Despite a compelling rationale, evidence is scant that adding sitters to usual care reduces falls. Primary Funding Source: Veterans Affairs Quality Enhancement Research Initiative. (PROSPERO: CRD42019127424)

Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial: Annals of Internal Medicine: Vol 172, No 9

Background: Studies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD). Objective: To assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD. Design: Multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842) Setting: 57 Parkinson Study Group sites in North America. Participants: Patients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment. Intervention: 5 mg of immediate-release isradipine twice daily or placebo for 36 months. Measurements: The primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication “ON” state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures. Results: 336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of −0.27 (CI, −3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness. Limitation: The isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects. Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD. Primary Funding Source: National Institute of Neurological Disorders and Stroke.

Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation

Background: Early rehabilitation after stroke is essential to help reduce disability. Purpose: To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke. Data Sources: English-language searches of multiple electronic databases from April 2009 through July 2018; targeted searches to December 2018 for studies of selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors. Study Selection: 19 systematic reviews and 37 randomized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke. Data Extraction: One investigator abstracted the data, and quality and GRADE assessment were checked by a second investigator. Data Synthesis: Most interventions (for example, SSRIs, mental practice, mirror therapy) did not improve motor function. High-quality evidence did not support use of fluoxetine to improve motor function. Moderate-quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living (ADLs). Low-quality evidence supported use of robotic arm training to improve ADLs. Low-quality evidence indicated that antidepressants may reduce depression, whereas the frequency and severity of antidepressant-related adverse effects was unclear. Low-quality evidence suggested that cognitive behavioral therapy and exercise, including mind–body exercise, may reduce symptoms of depression and anxiety. Limitation: Studies were of poor quality, interventions and comparators were heterogeneous, and evidence on harms was scarce. Conclusion: Cardiorespiratory training, repetitive task training, and transcranial direct current stimulation may improve ADLs in adults with stroke. Cognitive behavioral therapy, exercise, and SSRIs may reduce symptoms of poststroke depression, but use of SSRIs to prevent depression or improve motor function was not supported. Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.

Growth and Distribution of Buprenorphine-Waivered Providers in the United States, 2007–2017

Cost-Effectiveness of Transitional Care Services After Hospitalization With Heart Failure

Background: Patients with heart failure (HF) discharged from the hospital are at high risk for death and rehospitalization. Transitional care service interventions attempt to mitigate these risks. Objective: To assess the cost-effectiveness of 3 types of postdischarge HF transitional care services and standard care. Design: Decision analytic microsimulation model. Data Sources: Randomized controlled trials, clinical registries, cohort studies, Centers for Disease Control and Prevention life tables, Centers for Medicare & Medicaid Services data, and National Inpatient Sample (Healthcare Cost and Utilization Project) data. Target Population: Patients with HF who were aged 75 years at hospital discharge. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Disease management clinics, nurse home visits (NHVs), and nurse case management. Outcome Measures: Quality-adjusted life-years (QALYs), costs, net monetary benefits, and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis: All 3 transitional care interventions examined were more costly and effective than standard care, with NHVs dominating the other 2 interventions. Compared with standard care, NHVs increased QALYs (2.49 vs. 2.25) and costs ($81 327 vs. $76 705), resulting in an ICER of $19 570 per QALY gained. Results of Sensitivity Analysis: Results were largely insensitive to variations in in-hospital mortality, age at baseline, or costs of rehospitalization. Probabilistic sensitivity analysis confirmed that transitional care services were preferred over standard care in nearly all 10 000 samples, at willingness-to-pay thresholds of $50 000 or more per QALY gained. Limitation: Transitional care service designs and implementations are heterogeneous, leading to uncertainty about intervention effectiveness and costs when applied in particular settings. Conclusion: In older patients with HF, transitional care services are economically attractive, with NHVs being the most cost-effective strategy in many situations. Transitional care services should become the standard of care for postdischarge management of patients with HF. Primary Funding Source: Swiss National Science Foundation, Research Council of Norway, and an Intermountain–Stanford collaboration.

Diabetes Technology: Review of the 2019 American Diabetes Association Standards of Medical Care in Diabetes

Description: The American Diabetes Association (ADA) annually updates its Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. Methods: The ADA Professional Practice Committee comprises physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts. To develop the 2019 standards, the committee continuously searched MEDLINE through November 2018 to consider and review studies, particularly high-quality trials including persons with diabetes, for potential incorporation into recommendations. It also solicited feedback from the larger clinical community. Recommendations: This synopsis focuses on selected guidance relating to use of diabetes technology in adults with diabetes. Recommendations address self-monitoring of blood glucose, continuous glucose monitors, and automated insulin delivery systems.

Presenting Risks and Benefits: Helping the Data Monitoring Committee Do Its Job

Data monitoring committees (DMCs), or data and safety monitoring boards, protect clinical trial participants by conducting benefit–risk assessments during the course of a clinical trial. These evaluations may be improved by broader access to data and more effective analyses and presentation. Data monitoring committees should have access to all data, including efficacy data, at each interim review. The DMC reports should include graphical presentations that summarize benefits and harms in efficient ways. Benefit–risk assessments should include summaries that are consistent with the intention-to-treat principle and have a pragmatic focus. This article provides examples of graphical summaries that integrate benefits and harms, and proposes that such summaries become standard in DMC reports.