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As opioid prescribing has declined, it is unclear how the landscape of prescription pain treatment across the U.S. has changed. We used nationally-representative data from the Medical Expenditure Health Survey, 2014 to 2018 to examine trends in prescriptions for opioid and non-opioid pain medications, including acetaminophen, non-steroidal anti-inflammatory drugs, gabapentinoids, and antidepressants among U.S. adults with self-reported pain. Overall, from 2014 to 2018, the percentage of participants receiving a prescription for opioids declined, (38.8% vs 32.8%), remained stable for non-steroidal anti-inflammatory drugs (26.8% vs 27.7%), and increased for acetaminophen (1.6% vs 2.3%), antidepressants (9.6% vs 12.0%) and gabapentinoids (13.2% vs 19.0%). In this period, the adjusted odds of receiving an opioid prescription decreased (aOR=.93, 95% CI=.90-.96), while the adjusted odds of receiving antidepressant, gabapentinoid and acetaminophen prescriptions increased (antidepressants: aOR=1.08, 95% CI=1.03-1.13 gabapentinoids: aOR=1.11, 95% CI=1.06-1.17; acetaminophen: aOR=1.10, 95% CI: 1.02-1.20). Secondary analyses stratifiying within the 2014 to 2016 and 2016 to 2018 periods revealed particular increases in prescriptions for gabapentinoids (aOR=1.13, 95% CI=1.05-1.21) and antidepressants (aOR=1.23, 95% CI=1.12-1.35) since 2016. PERSPECTIVE: These data demonstrate that physicians are increasingly turning to CDC-recommended non-opioid medications for pain management, particularly antidepressants and gabapentinoids. However, evidence for these medications' efficacy in treating numerous common pain conditions, including low back pain, remains limited.

OBJECTIVES This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. BACKGROUND The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. METHODS We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). RESULTS We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. CONCLUSIONS In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i. (J Am Coll Cardiol HF 2022;10:73-84) (c) 2022 by the American College of Cardiology Foundation.

Systemic sclerosis (SSc) is a rare, systemic autoimmune disease of unknown etiology. Among the systemic rheumatic diseases, SSc carries the highest mortality, in part due to the historical lack of disease modifying therapies. Recently, landmark randomized controlled trials (RCTs) have been conducted that have illustrated the heterogeneous nature of SSc and furthered our understanding of the key inflammatory and fibrotic pathways involved in SSc pathogenesis. Although SSc affects various organ systems, RCTs have focused on investigating treatments for diffuse cutaneous sclerosis (dcSSc) and interstitial lung disease (ILD). While recent RCTs for dcSSc have failed to demonstrate a treatment benefit, the outcomes of two RCTs led to the approval of two novel therapies for SSc-ILD: nintedanib and tocilizumab. This review summarizes the salient outcome data from recent SSc trials within a practical clinical framework and points out gaps in knowledge that may help inform the design of future SSc studies.