NEJM evidence最新文献

AbstractIn 2016, many clinicians and investigators in the field of sleep apnea were surprised when a large multinational clinical trial of continuous positive airway pressure (CPAP) therapy failed to demonstrate a reduction in cardiovascular events in patients with sleep apnea and established cardiovascular disease. When a review of the trial data suggested that CPAP nonadherence among trial participants might explain the negative results, it became clear that new approaches were needed. In this Clinical Trials Case Study, we share our experience designing a trial to evaluate a peer-support strategy to improve CPAP adherence. We address how patients were the drivers of research ideas and discuss how the return on investment in such patient-engaged approaches to research can be high for patients, trialists, and, ultimately, public health. Our experience could serve as a road map for investigators who have the same trepidation as we once did to create, engage, and empower a patient-stakeholder committee. Such knowledge could help clinical trials accomplish the stated goals for various chronic medical conditions.

Background: Adverse cardiac remodeling is common in people with chronic kidney disease and contributes to increased cardiovascular risk. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown cardioprotective effects in patients with chronic kidney disease, the underlying mechanisms are still not completely understood. This trial evaluated the impact of SGLT2 inhibitors on cardiac structure and function in patients with chronic kidney disease.

Methods: Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease (DECODE-CKD) was a 6-month, single-center, randomized, double-blind trial comparing dapagliflozin with placebo in patients with an estimated glomerular filtration rate of 20 to 59 or greater than or equal to 60 ml/minute/1.73 m² with a urine albumin-creatinine ratio greater than or equal to 200 mg/g. Participants underwent serial echocardiography and biomarker assessment. The primary end point was the change in left ventricular mass index. Secondary end points included changes in systolic and diastolic function, high-sensitivity troponin I, pro-B-type natriuretic peptides, hemoglobin, the urine albumin-creatinine ratio, and creatinine.

Results: Of 268 screened individuals, 222 were randomly assigned. The mean age was 67.5 years; 29.3% were women. Cardiovascular disease was present at enrollment in 34.2%, heart failure in 5.9%, hypertension in 75.7%, and diabetes in 8.6%. The most common causes of chronic kidney disease were hypertensive nephropathy (25.7%) and polycystic kidney disease (16.7%). The estimated mean difference in left ventricular mass index between the dapagliflozin group compared with placebo was -8.44 g/m² (95% confidence interval, -11.83 to -5.06; P<0.001). Effects were consistent across key subgroups, including by demographics, cardiovascular history, biomarkers, and chronic kidney disease etiology. The rate of serious adverse events was similar between the groups.

Conclusions: In a heterogeneous population of patients with chronic kidney disease, dapagliflozin significantly reduced left ventricular mass index compared with placebo. These findings provide mechanistic insights into the early treatment benefits of SGLT2 inhibitors seen previously in chronic kidney disease. Further research is needed to replicate and further define these early treatment benefits. (Funded by the Danish Cardiovascular Academy and Novo Nordisk Foundation; ClinicalTrials.gov number, NCT05359263.).

AbstractDirect-to-consumer genetic testing has become increasingly popular, offering individuals easy access to genetic data without the involvement of health care professionals. However, as availability grows, clinicians face challenges in interpreting and integrating this information into clinical care. This review provides insights for health professionals about the evolving landscape of direct-to-consumer genetic testing, with a focus on test offerings, limitations, challenges, and ethical concerns. It also highlights issues that can arise with direct-to-consumer genetic testing in the pediatric setting. Clinicians can play a pivotal role in guiding patients and families through the complexities of direct-to-consumer genetic testing, ensuring that decisions are informed and risks are minimized.

AbstractGenetics plays an important role in the response to some drugs. Clinical pharmacogenetic testing can be used to guide pharmacotherapy selection or dosing to optimize outcomes. Growing evidence over the past decade has led to the identification of numerous pharmacogenetic associations, which have been integrated across multiple clinical areas, including cardiology, primary care, pain management, surgery, and oncology. Increased access to pharmacogenetic testing via national laboratories and pharmacogenetic testing companies has facilitated uptake and heightened public interest. While clinical adoption of pharmacogenetics has increased, challenges remain, including a lack of clinician confidence in navigating the logistics of testing and applying pharmacogenetics results in patient care; limited reimbursement for testing in some cases; the need for extensive outcomes and economic data; and limited inclusion of testing in clinical guidelines. Future opportunities include the broader use of multigene panels, enhanced clinician training, the integration of pharmacogenetic data within electronic health records, and increased documentation of outcomes data from real-world implementation to support insurance coverage.

Background: Influenza vaccination rates remain suboptimal despite strong evidence of benefit. Electronic letters emphasizing the cardiovascular benefits of vaccination increased uptake in Denmark; whether this strategy is effective in a diverse U.S. population is unknown.

Methods: In this prospective, randomized, open, blinded end point trial involving a multiregional health care system, adults were randomly assigned 1:1:1:1 to receive cardiovascular-focused messaging versus usual care messaging to encourage influenza vaccination at two trial time points, yielding four groups, with each in receipt of either two rounds of cardiovascular-focused nudges; a cardiovascular-focused nudge followed by usual care communication; usual care communication followed by a cardiovascular-focused nudge; or two rounds of usual care communication. The primary end point was influenza vaccination receipt through January 1, 2025. Outcomes were assessed across six coprimary comparisons.

Results: Overall, 3,668,428 adults were randomly assigned across three U.S. states and Washington, DC. Participants had a mean (±SD) age of 48.36 (±18.11) years, 52.87% (n=1,939,352) were women, 10.53% (n=386,393) were Black, and 702,493 (19.15%) had cardiovascular disease. Overall vaccination rate at the end of the trial was 32.46%. Compared with participants who received two rounds of usual care communication, those receiving cardiovascular-focused messaging at any time point had similar vaccination rates (32.41% vs. 32.60%; absolute change, -0.19 percentage points; 99.2% confidence interval, -0.34 to -0.04). Time to vaccination did not differ.

Conclusions: In a large individually randomized trial embedded in routine care across a national U.S. health system, a cardiovascular-focused nudge intervention did not increase influenza vaccination rates on a background of low uptake. Nevertheless, this trial illustrates the feasibility of conducting large care-embedded trials of nudges in U.S. health systems. (Funded by Kaiser Permanente's Garfield Memorial Fund; trial registration, ClinicalTrials.gov NCT06571747.).

Background: Research participants have expressed a clear preference for receiving research results. Although researchers have many obligations toward research participants, these do not typically include disclosure of research results. The primary objective of this survey was to describe the opinions of participants or their substitute decision-makers regarding the communication of results from a trial conducted in the intensive care unit.

Methods: A recent international randomized trial of vitamin C versus placebo for sepsis showed harm from vitamin C in the primary analysis. We sent Canadian participants in this trial a letter offering a lay summary of the trial results. If the participant had died or lacked capacity, the letter was sent to their substitute decision-maker. The primary outcome was the proportion of recipients who opted out of receiving the trial summary. Recipients who agreed to receive trial results were invited to complete a survey afterward. Respondents could request to know their treatment assignment; if they did, they were invited to complete the same survey after unblinding.

Results: Of 340 potential respondents, 24 (7%) declined to receive trial results (13 participants, 11 substitute decision-makers). Of 316 individuals who received the summary, 139 (44%) completed the survey and, of those, 98 (71%) requested information on treatment assignment. Many did not remember the initial trial (40 out of 93 [43%] participants and 21 out of 31 [68%] substitute decision-makers), but 85% of respondents (118 out of 139) thought that the trial was necessary. The most common views after receiving the trial results were satisfaction (n=52, 37%) and surprise (n=40, 29%). Most respondents stated that researchers should systematically disclose trial results (n=127, 91%) and treatment assignment (n=111, 80%) to participants or substitute decision-makers.

Conclusions: Participants and their substitute decision-makers in a critical care trial who responded to our survey largely favored being informed of trial results, and they expressed understanding of the value of research, even when experimental interventions prove harmful. (Funded by the Lotte and John Hecht Foundation and the Canadian Critical Care Research Coordinators Group.).