PreScription DigitaL ThErapEutic for Patients with Insomnia (SLEEP-I): a protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Cognitive behavioural therapy for insomnia (CBT-I) is effective at treating chronic insomnia, yet in-person CBT-I can often be challenging to access. Prior studies have used technology to bridge barriers but have been unable to extensively assess the impact of the digital therapeutic on real-world patient experience and multidimensional outcomes. Among patients with insomnia, our aim is to determine the impact of a prescription digital therapeutic (PDT) (PEAR-003b, FDA-authorised as Somryst; herein called PDT) that provides mobile-delivered CBT-I on patient-reported outcomes (PROs) and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a pragmatically designed, prospective, multicentre randomised controlled trial that leverages Hugo, a unique patient-centred health data-aggregating platform for data collection and patient follow-up from Hugo Health. A total of 100 participants with insomnia from two health centres will be enrolled onto the Hugo Health platform, provided with a linked Fitbit (Inspire 2) to track activity and then randomised 1:1 to receive (or not) the PDT for mobile-delivered CBT-I (Somryst). The primary outcome is a change in the insomnia severity index score from baseline to 9-week postrandomisation. Secondary outcomes include healthcare utilisation, health utility scores and clinical outcomes; change in sleep outcomes as measured with sleep diaries and a change in individual PROs including depressive symptoms, daytime sleepiness, health status, stress and anxiety. For those allocated to the PDT, we will also assess engagement with the PDT. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University and the Mayo Clinic have approved the trial protocol. This trial will provide important data to patients, clinicians and policymakers about the impact of the PDT device delivering CBT-I on PROs, clinical outcomes and healthcare utilisation. Findings will be disseminated to participants, presented at professional meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04909229.

Real-world Cardiovascular Outcomes Associated With Degarelix vs Leuprolide for Prostate Cancer Treatment.

Importance: With a growing interest in the use of real-world evidence for regulatory decision-making, it is important to understand whether real-world data can be used to emulate the results of randomized clinical trials. Objective: To use electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease). Design, Setting, and Participants: This retrospective, propensity-matched cohort study included adult men with a diagnosis of prostate cancer and cardiovascular disease who initiated either degarelix or leuprolide between December 24, 2008, and June 30, 2019. Participants were commercially insured individuals and Medicare Advantage beneficiaries included in a large US administrative claims database. Exposures: Degarelix or leuprolide. Main Outcomes and Measures: The primary end point was time to first occurrence of a major adverse cardiovascular event (MACE), defined as death due to any cause, myocardial infarction, or stroke, analogous to the PRONOUNCE trial. Secondary end points were time to death due to any cause, myocardial infarction, stroke, and angina. Cox proportional hazards regression was used to evaluate primary and secondary end points. Results: A total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) met the PRONOUNCE trial eligibility criteria and were included in this study. Overall, 165 participants (2.1%) were Asian, 1390 (17.8%) were Black, 663 (8.5%) were Hispanic, and 5258 (67.4%) were White. The mean (SD) age was 74.4 (7.4) years. Among 2226 propensity score-matched patients, no significant difference was observed in the risk of MACE for patients taking degarelix vs those taking leuprolide (10.18 vs 8.60 events per 100 person-years; hazard ratio [HR], 1.18; 95% CI, 0.86-1.61). Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95% CI, 0.60-2.25), stroke (HR, 0.92; 95% CI, 0.45-1.85), or angina (HR, 1.36; 95% CI, 0.43-4.27). Conclusions and Relevance: In this emulation of a clinical trial of men with cardiovascular disease undergoing treatment for prostate cancer, degarelix was not associated with a lower risk of cardiovascular events than leuprolide. Comparison of these data with PRONOUNCE trial results, when published, will help enhance our understanding of the appropriate role of using real-world data to emulate clinical trials.

Use of Mechanical Circulatory Support Devices Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Importance: Mechanical circulatory support (MCS) devices, including intravascular microaxial left ventricular assist devices (LVADs) and intra-aortic balloon pumps (IABPs), are used in patients who undergo percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock despite limited evidence of their clinical benefit. Objective: To examine trends in the use of MCS devices among patients who underwent PCI for AMI with cardiogenic shock, hospital-level use variation, and factors associated with use. Design, Setting, and Participants: This cross-sectional study used the CathPCI and Chest Pain-MI Registries of the American College of Cardiology National Cardiovascular Data Registry. Patients who underwent PCI for AMI complicated by cardiogenic shock between October 1, 2015, and December 31, 2017, were identified from both registries. Data were analyzed from October 2018 to August 2020. Exposures: Therapies to provide hemodynamic support were categorized as intravascular microaxial LVAD, IABP, TandemHeart, extracorporeal membrane oxygenation, LVAD, other devices, combined IABP and intravascular microaxial LVAD, combined IABP and other device (defined as TandemHeart, extracorporeal membrane oxygenation, LVAD, or another MCS device), or medical therapy only. Main Outcomes and Measures: Use of MCS devices overall and specific MCS devices, including intravascular microaxial LVAD, at both patient and hospital levels and variables associated with use. Results: Among the 28 304 patients included in the study, the mean (SD) age was 65.4 (12.6) years and 18 968 were men (67.0%). The overall MCS device use was constant from the fourth quarter of 2015 to the fourth quarter of 2017, although use of intravascular microaxial LVADs significantly increased (from 4.1% to 9.8%; P < .001), whereas use of IABPs significantly decreased (from 34.8% to 30.0%; P < .001). A significant hospital-level variation in MCS device use was found. The median (interquartile range [IQR]) proportion of patients who received MCS devices was 42% (30%-54%), and the median proportion of patients who received intravascular microaxial LVADs was 1% (0%-10%). In multivariable analyses, cardiac arrest at first medical contact or during hospitalization (odds ratio [OR], 1.82; 95% CI, 1.58-2.09) and severe left main and/or proximal left anterior descending coronary artery stenosis (OR, 1.36; 95% CI, 1.20-1.54) were patient characteristics that were associated with higher odds of receiving intravascular microaxial LVADs only compared with IABPs only. Conclusions and Relevance: This study found that, among patients who underwent PCI for AMI complicated by cardiogenic shock, overall use of MCS devices was constant, and a 2.5-fold increase in intravascular microaxial LVAD use was found along with a corresponding decrease in IABP use and a significant hospital-level variation in MCS device use. These trends were observed despite limited clinical trial evidence of improved outcomes associated with device use.

Association of Use of an Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump With In-Hospital Mortality and Major Bleeding Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Importance: Acute myocardial infarction (AMI) complicated by cardiogenic shock is associated with substantial morbidity and mortality. Although intravascular microaxial left ventricular assist devices (LVADs) provide greater hemodynamic support as compared with intra-aortic balloon pumps (IABPs), little is known about clinical outcomes associated with intravascular microaxial LVAD use in clinical practice. Objective: To examine outcomes among patients undergoing percutaneous coronary intervention (PCI) for AMI complicated by cardiogenic shock treated with mechanical circulatory support (MCS) devices. Design, Setting, and Participants: A propensity-matched registry-based retrospective cohort study of patients with AMI complicated by cardiogenic shock undergoing PCI between October 1, 2015, and December 31, 2017, who were included in data from hospitals participating in the CathPCI and the Chest Pain-MI registries, both part of the American College of Cardiology's National Cardiovascular Data Registry. Patients receiving an intravascular microaxial LVAD were matched with those receiving IABP on demographics, clinical history, presentation, infarct location, coronary anatomy, and clinical laboratory data, with final follow-up through December 31, 2017. Exposures: Hemodynamic support, categorized as intravascular microaxial LVAD use only, IABP only, other (such as use of a percutaneous extracorporeal ventricular assist system, extracorporeal membrane oxygenation, or a combination of MCS device use), or medical therapy only. Main Outcomes and Measures: The primary outcomes were in-hospital mortality and in-hospital major bleeding. Results: Among 28 304 patients undergoing PCI for AMI complicated by cardiogenic shock, the mean (SD) age was 65.0 (12.6) years, 67.0% were men, 81.3% had an ST-elevation myocardial infarction, and 43.3% had cardiac arrest. Over the study period among patients with AMI, an intravascular microaxial LVAD was used in 6.2% of patients, and IABP was used in 29.9%. Among 1680 propensity-matched pairs, there was a significantly higher risk of in-hospital death associated with use of an intravascular microaxial LVAD (45.0%) vs with an IABP (34.1% [absolute risk difference, 10.9 percentage points {95% CI, 7.6-14.2}; P < .001) and also higher risk of in-hospital major bleeding (intravascular microaxial LVAD [31.3%] vs IABP [16.0%]; absolute risk difference, 15.4 percentage points [95% CI, 12.5-18.2]; P < .001). These associations were consistent regardless of whether patients received a device before or after initiation of PCI. Conclusions and Relevance: Among patients undergoing PCI for AMI complicated by cardiogenic shock from 2015 to 2017, use of an intravascular microaxial LVAD compared with IABP was associated with higher adjusted risk of in-hospital death and major bleeding complications, although study interpretation is limited by the observational design. Further research may be needed to understand optimal device choice for these patients.

Diet, Physical Activity, and Body Weight in Cancer Survivorship.

Diet, physical activity, and body weight have been shown to play an important role in cancer survivorship. The impact of each of these lifestyle factors differs slightly among cancer types, and adherence to recommended diet and physical activity guidelines has been associated with positive outcomes, including decrease in the risk of cancer recurrence and improvement of quality of life. Although there are compelling data that appropriate diet, physical activity, and body weight have beneficial effects in cancer survivorship, additional trials are needed to understand the relationship.