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Importance: Most adults 65 years or older have multiple chronic conditions. Managing these conditions with prescription drugs can be costly, particularly for older adults with limited incomes., Objective: To estimate hypothetical out-of-pocket costs associated with guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases among older adults with Medicare prescription drug plans (PDPs)., Design, Setting, and Participants: This retrospective cross-sectional study used 2009 and 2019 Medicare prescription drug plan formulary files to estimate annual out-of-pocket costs among hypothetical patients enrolled in Medicare Advantage or stand-alone Medicare Part D plans. A total of 3599 PDPs in 2009 and 3618 PDPs in 2019 were included after inclusion and exclusion criteria were applied. Costs associated with guideline-recommended medications for 8 of the most common chronic diseases (atrial fibrillation, chronic obstructive pulmonary disease [COPD], heart failure with reduced ejection fraction, hypercholesterolemia, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes), alone and in 2 clusters of commonly comorbid conditions, were examined., Main Outcomes and Measures: Annual out-of-pocket costs for each chronic condition, inflation adjusted to 2019 dollars., Results: Among 3599 Medicare PDPs in 2009, 1998 were Medicare Advantage plans and 1601 were stand-alone plans; among 3618 Medicare PDPs in 2019, 2719 were Medicare Advantage plans and 899 were stand-alone plans. For an older adult enrolled in any Medicare PDP in 2019, the median annual out-of-pocket costs for individual conditions varied, from a minimum of $32 (IQR, $6-$48) for guideline-recommended management of osteoporosis (a decrease from $128 [IQR, $102-$183] in 2009) to a maximum of $1579 (IQR, $1524-$2229) for guideline-recommended management of atrial fibrillation (an increase from $91 [IQR, $73-$124] in 2009). For an older adult with a cluster of 5 commonly comorbid conditions (COPD, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes) enrolled in any PDP, the median out-of-pocket cost in 2019 was $1999 (IQR, $1630-$2564), a 12% decrease from $2284 (IQR, $1920-$3107) in 2009. For an older adult with all 8 chronic conditions (atrial fibrillation, COPD, diabetes, hypercholesterolemia, heart failure, hypertension, osteoarthritis, and osteoporosis) enrolled in any PDP, the median out-of-pocket cost in 2019 was $3630 (IQR, $3234-$5197), a 41% increase from $2571 (IQR, $2185-$3719) in 2009., Conclusions and Relevance: In this cross-sectional study, out-of-pocket costs for guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases varied by condition. Although costs generally decreased between 2009 and 2019, particularly with regard to conditions for which generic drugs were available, out-of-pocket costs remained high and may have presented a substantial financial burden for Medicare beneficiaries, especially older adults with conditions for which brand-name drugs were guideline recommended.

Objective: To evaluate the association between pharmaceutical industry payments to rheumatologists and their prescribing behaviors., Methods: A cross-sectional analysis was conducted of Medicare Part B Public Use File, Medicare Part D Public Use File, and Open Payments data for 2013 to 2015. Prescription drugs responsible for 80% of the total Medicare pharmaceutical expenditures in rheumatology were analyzed. We calculated the mean annual drug cost per beneficiary per year, the percentage of rheumatologists who received payments, and the median annual payment per physician per drug per year. Industry payments were categorized as food/beverage and consulting/compensation. Multivariable regression models were used to assess associations between industry payments and both prescribing patterns and prescription drug expenditures., Results: Of 4822 rheumatologists in the Medicare prescribing databases, 3729 received any payment from a pharmaceutical company during this time frame. Food/beverage payments were associated with an increased proportion of prescriptions for the related drugs (range, 1.5% to 4.5%) and an increased proportion of annual Medicare spending for the related drugs (range, 3% to 23%). For every $100 in food/beverage payments, the probability of prescribing increased (range, 1.5% to 14% for most drugs) and Medicare reimbursements increased (range, 6% to 44% for most drugs). Consulting/compensation payments were associated with an increased proportion of prescriptions (range, 1.2% to 1.6%) and an increased proportion of annual Medicare spending (range, 1% to 2%). For every $1000 in consulting/compensation payments, both the probability of prescribing increased (5% or less for most drugs) and Medicare reimbursements increased (less than 10% for most drugs)., Conclusion: Payments to rheumatologists by pharmaceutical companies are associated with increased probability of prescribing and Medicare spending., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The American Board of Plastic Surgery has been collecting practice data on metacarpal fracture operative repair since 2006 as part of its Continuous Certification process. These data allow plastic surgeons to compare their surgical experience to national trends. Additionally, these data present the opportunity to analyze those trends in relation to evidence-based medicine., Methods: Data on metacarpal fracture operative repair from May 2006 to December 2014 were reviewed and compared with those from January 2015 to March 2020. National practice trends observed in these data were evaluated and reviewed alongside published literature and evidence-based medicine., Results: In total, 1160 metacarpal fracture repair cases were included. Outpatient (as opposed to inpatient) operative repairs have been trending upward, from 50% to 61% ( P < 0.001). Most repairs were performed under general anesthesia (68%), and there was a decrease in the use of regional anesthesia between our two cohorts (14%-9%; P = 0.01). An open reduction with internal fixation was the most popular technique (51%), and a decrease in the use of closed reduction with splinting was observed (16%-10%; P = 0.001). Stiffness was the most commonly reported adverse event. Topics addressed in evidence-based medicine articles but not tracer data included interosseous wiring, which has shown success in spiral shaft fracture treatment with minimal complications, and nonoperative management., Conclusion: As evidence-based recommendations continue to change with additional research inquiry, tracer data can provide an excellent overview of the current practice of metacarpal fracture repair and how effectively physicians adapt to remain aligned with best practices., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background Guidelines promote shared decision-making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within-encounter SDM tool to usual care (UC) increases patient involvement in decision-making and clinician satisfaction, without affecting encounter length. We aimed to estimate the extent to which use of an SDM tool changed adherence to the decided care plan and clinical safety end points. Methods and Results We conducted a multicenter, encounter-level, randomized trial assessing the efficacy of UC with versus without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice) in patients with nonvalvular atrial fibrillation considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months after enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled for direct oral anticoagulant, and as time in therapeutic range for warfarin). We also noted any strokes, transient ischemic attacks, major bleeding, or deaths as safety end points. We enrolled 922 evaluable patient encounters (Anticoagulation Choice=463, and UC=459), of which 814 (88%) had pharmacy and clinical follow-up. We found no differences between arms in either primary adherence (78% of patients in the SDM arm filled their first prescription versus 81% in UC arm) or secondary adherence to anticoagulation (percentage days covered of the direct oral anticoagulant was 74.1% in SDM versus 71.6% in UC; time in therapeutic range for warfarin was 66.6% in SDM versus 64.4% in UC). Safety outcomes, mostly bleeds, occurred in 13% of participants in the SDM arm and 14% in the UC arm. Conclusions In this large, randomized trial comparing UC with a tool to promote SDM against UC alone, we found no significant differences between arms in primary or secondary adherence to anticoagulation or in clinical safety outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: clinicaltrials.gov. Identifier: NCT02905032.

Background: Patient-clinician secure messaging is an important function in patient portals and enables patients and clinicians to communicate on a wide spectrum of issues in a timely manner. With its growing adoption and patient engagement, it is time to comprehensively study the secure messages and user behaviors in order to improve patient-centered care., Objective: The aim of this paper was to analyze the secure messages sent by patients and clinicians in a large multispecialty health system at Mayo Clinic, Rochester., Methods: We performed message-based, sender-based, and thread-based analyses of more than 5 million secure messages between 2010 and 2017. We summarized the message volumes, patient and clinician population sizes, message counts per patient or clinician, as well as the trends of message volumes and user counts over the years. In addition, we calculated the time distribution of clinician-sent messages to understand their workloads at different times of a day. We also analyzed the time delay in clinician responses to patient messages to assess their communication efficiency and the back-and-forth rounds to estimate the communication complexity., Results: During 2010-2017, the patient portal at Mayo Clinic, Rochester experienced a significant growth in terms of the count of patient users and the total number of secure messages sent by patients and clinicians. Three clinician categories, namely "physician-primary care," "registered nurse-specialty," and "physician-specialty," bore the majority of message volume increase. The patient portal also demonstrated growing trends in message counts per patient and clinician. The "nurse practitioner or physician assistant-primary care" and "physician-primary care" categories had the heaviest per-clinician workload each year. Most messages by the clinicians were sent from 7 AM to 5 PM during a day. Yet, between 5 PM and 7 PM, the physicians sent 7.0% (95,785/1,377,006) of their daily messages, and the nurse practitioner or physician assistant sent 5.4% (22,121/408,526) of their daily messages. The clinicians replied to 72.2% (1,272,069/1,761,739) patient messages within 1 day and 90.6% (1,595,702/1,761,739) within 3 days. In 95.1% (1,499,316/1,576,205) of the message threads, the patients communicated with their clinicians back and forth for no more than 4 rounds., Conclusions: Our study found steady increases in patient adoption of the secure messaging system and the average workload per clinician over 8 years. However, most clinicians responded timely to meet the patients' needs. Our study also revealed differential patient-clinician communication patterns across different practice roles and care settings. These findings suggest opportunities for care teams to optimize messaging tasks and to balance the workload for optimal efficiency., (©Ming Huang, Jungwei Fan, Julie Prigge, Nilay D Shah, Brian A Costello, Lixia Yao. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.01.2022.)

Background: Several vaccines are now available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. Vaccine impact on asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is largely unknown., Methods: We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39 156) within a large US healthcare system who underwent 48 333 preprocedural SARS-CoV-2 molecular screening tests between 17 December 2020 and 8 February 2021. The primary exposure of interest was vaccination with ≥1 dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk (RR) of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received ≥1 dose of vaccine compared with persons who had not received vaccine during the same time period. RR was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs nonlocal), healthcare system regions, and repeated screenings among patients using mixed-effects log-binomial regression., Results: Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3006 tests and 1436 (3.2%) of 45 327 tests performed on vaccinated and unvaccinated patients, respectively (RR, .44; 95% CI, .33-.60; P < .0001). Compared with unvaccinated patients, risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after the first dose (RR, .21; 95% CI, .12-.37; P < .0001) and >0 days after the second dose (RR, .20; 95% CI, .09-.44; P < .0001) in the adjusted analysis., Conclusions: COVID-19 vaccination with an mRNA-based vaccine showed a significant association with reduced risk of asymptomatic SARS-CoV-2 infection as measured during preprocedural molecular screening. Results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Importance: Social determinants of health play a role in diabetes management and outcomes, including potentially life-threatening complications of severe hypoglycemia and diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS). Although several person-level socioeconomic factors have been associated with these complications, the implications of area-level socioeconomic deprivation are unknown., Objective: To examine the association between area-level deprivation and the risks of experiencing emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises (ie, DKA or HHS)., Design, Setting, and Participants: This cohort study used deidentified administrative claims data for privately insured individuals and Medicare Advantage beneficiaries across the US. The analysis included adults with diabetes who met the claims criteria for diabetes between January 1, 2016, and December 31, 2017. Data analyses were performed from November 17, 2020, to November 11, 2021., Exposures: Area deprivation index (ADI) was derived for each county for 2016 and 2017 using 17 county-level indicators from the American Community Survey. ADI values were applied to patients who were living in each county based on their index dates and were categorized according to county-level ADI quintile (with quintile 1 having the least deprivation and quintile 5 having the most deprivation)., Main Outcomes and Measures: The numbers of emergency department visits or hospitalizations related to the primary diagnoses of hypoglycemia and DKA or HHS (ascertained using validated diagnosis codes in the first or primary position of emergency department or hospital claims) between 2016 and 2019 were calculated for each ADI quintile using negative binomial regression models and adjusted for patient age, sex, health plan type, comorbidities, glucose-lowering medication type, and percentage of White residents in the county., Results: The study population included 1 116 361 individuals (563 943 women [50.5%]), with a mean (SD) age of 64.9 (13.2) years. Of these patients, 343 726 (30.8%) resided in counties with the least deprivation (quintile 1) and 121 810 (10.9%) lived in counties with the most deprivation (quintile 5). Adjusted rates of severe hypoglycemia increased from 13.54 (95% CI, 12.91-14.17) per 1000 person-years in quintile 1 counties to 19.13 (95% CI, 17.62-20.63) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.41 (95% CI, 1.29-1.54; P < .001). Adjusted rates of DKA or HHS increased from 7.49 (95% CI, 6.96-8.02) per 1000 person-years in quintile 1 counties to 8.37 (95% CI, 7.50-9.23) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.12 (95% CI, 1.00-1.25; P = .049)., Conclusions and Relevance: This study found that living in counties with a high area-level deprivation was associated with an increased risk of severe hypoglycemia and DKA or HHS. The concentration of these preventable events in areas of high deprivation signals the need for interventions that target the structural barriers to optimal diabetes management and health.

Objectives: This study was undertaken to measure the concerns of students whose medical schools do not have a plastic surgery training program to help educators better understand their perspectives. This is essential to improve plastic surgery education for almost 50% of students in the United States at institutions without a residency program., Design: An anonymous survey was distributed to the clerkship directors of the applicable medical schools. They were then asked to forward this survey to their student body. The survey was divided as follows: demographics; exposure to plastic surgery; mentorship; suggestions for improvement; perceived impact on matching., Results: We received 265 responses from 16 unique institutions. About 38% consider themselves underrepresented in medicine. The most common initial professional exposure to plastic surgery was shadowing (20%). About 10% reported exposure to plastic surgery in their school curriculum. About 51% reported having no professional exposure to plastic surgery. About 89% did not identify a mentor. All students applying to away rotations reported difficulties facilitating these sub-internships. About 64% felt extremely concerned about matching., Conclusions: Students from schools without plastic surgery training programs are at a disadvantage. The academic community needs to support these students to achieve a more diverse field. All students should be given an introduction to plastic surgery as part of their curriculum, and they should be encouraged to explore a career in plastic surgery as a realistic option. If 1 perceives themselves as non-competitive due to institutional shortcomings, this will translate into a non-competitive applicant and discourage our specialty's serious pursuit by almost half the country's medical students., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (ESKD)., Research Design and Methods: This was a nationwide, retrospective study of adults (≥18 years old) with diabetes/ESKD, from the United States Renal Data System registry, between 2013 and 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1,000 person-years. Event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen, and U.S. region., Results: Among 521,789 adults with diabetes/ESKD (median age 65 years [interquartile range 57-73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1,000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, respectively, the risks decreased with age and were lowest in older patients (≥75 vs. 18-44 years old: incidence rate ratio 0.35, 95% CI 0.33-0.37, and 0.03, 0.02-0.03), women (1.09, 1.06-1.12, and 1.44, 1.35-1.54), and those with smoking (1.36, 1.28-1.43, and 1.71, 1.53-1.91), substance abuse (1.27, 1.15-1.42, and 1.53, 1.23-1.9), retinopathy (1.10, 1.06-1.15, and 1.36, 1.26-1.47), and insulin therapy (vs. no therapy; 0.60, 0.59-0.63, and 0.44, 0.39-0.48). For hypoglycemia, specifically, additional risk was conferred by Black race (1.11, 1.08-1.15) and amputation history (1.20, 1.13-1.27)., Conclusions: In this nationwide study of patients with diabetes/ESKD, hypoglycemic crises were threefold more common than hyperglycemic crises, greatly exceeding national reports in nondialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected., (© 2021 by the American Diabetes Association.)

Introduction: Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation., Methods and Analysis: We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings., Ethics and Dissemination: The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals., Trial Registration Number: NCT04468321., Competing Interests: Competing interests: SSD reports research funding from the National Heart, Lung, and Blood Institute (NHLBI, K12HL138046) of the National Institutes of Health (NIH), from the Medical Device Innovation Consortium (MDIC) as part of the National Evaluation System for health Technology Coordinating Center (NESTcc), Food and Drug Administration (FDA), Greenwall Foundation, and Arnold Ventures. NDS has received research support through Mayo Clinic from the FDA to establish the Yale–Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (CERSI, U01FD005938), from the Centers of Medicare and Medicaid Innovation under the Transforming Clinical Practice Initiative, from the Agency for Healthcare Research and Quality (AHRQ, U19HS024075, R01HS025164, R01HS025402, R03HS025517), from the NHLBI of the NIH (R56HL130496, R01HL131535), from the National Science Foundation, and from the Patient Centered Outcomes Research Institute to develop a Clinical Data Research Network. SV reports receiving funding support from the American College of Cardiology, Society of Thoracic Surgeons, and the NIH (R01 and Small Business Innovation Research BIR), FDA (through NESTcc), Abbott and Boston Scientific. He reports serving as a consultant or on the Advisory Board of Janssen, HeartFlow, the American College of Physicians, and Boston Scientific. ALB reported former employment at Apple and holds stock in Apple Inc. JVF reported salary support from the American College of Cardiology National Cardiovascular Data Registry and the NHLBI and consulting/advisory board fees from Boston Scientific, Medtronic, and Biosense Webster. JPP reports receiving grants for clinical research from Abbott, American Heart Association, Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, and Philips and serves as a consultant to Abbott, Abbvie, Ablacon, Altathera, ARCA Biopharma, Biotronik, Boston Scientific, Bristol Myers Squibb, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, Itamar, Pfizer, Sanofi, Philips, ResMed, and Up-to-Date. PAN receives research funding from NIH, including the NHLBI and the National Institute on Aging (NIA), AHRQ, FDA and the American Heart Association (AHA). He is a study investigator in an ablation trial sponsored by Medtronic. PAN and Mayo Clinic are involved in potential equity/royalty relationship with AliveCor. JSR received research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the FDA to establish Yale-Mayo Clinic CERSI program (U01FD005938), MDIC as part of the NESTcc, AHRQ (R01HS022882), NHLBI of the NIH (R01HS025164, R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International and to establish the Collaboration for Research Integrity and Transparency (CRIT) at Yale; in addition, JSR is an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the feasibility of using real-world data to assess the safety and effectiveness of two cardiac ablation catheters for the treatment of persistent atrial fibrillation and ischaemic ventricular tachycardia., Design: Retrospective cohort., Setting: Three health systems in the USA., Participants: Patients receiving ablation with the two ablation catheters of interest at any of the three health systems., Main Outcome Measures: Feasibility of identifying the medical devices and participant populations of interest as well as the duration of follow-up and positive predictive values (PPVs) for serious safety (ischaemic stroke, acute heart failure and cardiac tamponade) and effectiveness (arrhythmia-related hospitalisation) clinical outcomes of interest compared with manual chart validation by clinicians., Results: Overall, the catheter of interest for treatment of persistent atrial fibrillation was used for 4280 ablations and the catheter of interest for ischaemic ventricular tachycardia was used 1516 times across the data available within the three health systems. The duration of patient follow-up in the three health systems ranged from 91% to 97% at ≥7 days, 89% to 96% at ≥30 days, 77% to 90% at ≥6 months and 66% to 84% at ≥1 year. PPVs were 63.4% for ischaemic stroke, 96.4% for acute heart failure, 100% at one health system for cardiac tamponade and 55.7% for arrhythmia-related hospitalisation., Conclusions: It is feasible to use real-world health system data to evaluate the safety and effectiveness of cardiac ablation catheters, though evaluations must consider the implications of variation in follow-up and endpoint ascertainment among health systems., Competing Interests: Competing interests: SD receives research funding from the National Heart, Lung, and Blood Institute (NHLBI, K12HL138046) of the National Institutes of Health (NIH), from the Medical Device Innovation Consortium as part of the National Evaluation System for health Technology Coordinating Center (NESTcc), Food and Drug Administration (FDA), Greenwall Foundation, and Arnold Ventures. DJF has received educational grants from Boston Scientific, Medtronic, and Abbott; research grants from the American Heart Association, National Cardiovascular Data Registry, Boston Scientific, Abbott, Medtronic, Merit Medical, and Biosense Webster; consulting fees from Abbott and AtriCure. JGA has received consulting fees from Biosense Webster. JSR received research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration to establish Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938), from the Medical Device Innovation Consortium as part of NESTcc, from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International and to establish the Collaboration for Research Integrity and Transparency (CRIT) at Yale. NDS has received research support through Mayo Clinic from the Food and Drug Administration to establish the Yale–Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (U01FD005938), from the Centers of Medicare and Medicaid Innovation under the Transforming Clinical Practice Initiative, from the Agency for Healthcare Research and Quality (U19HS024075, R01HS025164, R01HS025402, R03HS025517), from the National Heart, Lung, and Blood Institute of the National Institutes of Health (R56HL130496, R01HL131535), from the National Science Foundation, and from the Patient Centered Outcomes Research Institute to develop a Clinical Data Research Network. PC is an employee of Johnson & Johnson; the manufacturer of the ThermoCool catheters, and Biosense Webster, is a Johnson & Johnson company. However, this study was a feasibility study to evaluate the suitability of the databases to conduct a study and no evaluation of the safety and effectiveness of any medical device was conducted in the study. PAN receives research funding from National Institutes of Health (NIH, including the NHLBI and the National Institute on Aging [NIA]), Agency for Healthcare Research and Quality (AHRQ), FDA, and the American Heart Association (AHA). He is a study investigator in an ablation trial sponsored by Medtronic. PAN and Mayo Clinic are involved in potential equity/royalty relationship with AliveCor. SZ is an employee of Johnson & Johnson; the manufacturer of the ThermoCool catheters and Biosense Webster, is a Johnson & Johnson company. WLS was an investigator for a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; is a technical consultant to Hugo Health, a personal health information platform, and cofounder of Refactor Health, an AI-augmented data management platform for healthcare; is a consultant for Interpace Diagnostics Group, a molecular diagnostics company. In the past 36 months, JPD has received research support from Medtronic and Johnson & Johnson. His non-dependent son is an employee of Boston Scientific., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Little is known on the persistence of asthma biologic use in clinical practice., Objective: To evaluate the persistence of asthma biologic use and time to clinical response in clinical practice., Methods: A cohort of people with asthma who used at least 1 asthma biologic was constructed using data from 2003 to 2019 in the OptumLabs Data Warehouse. Treatment persistence was defined by the length of time that a person continuously used an asthma biologic, allowing for a lapse in use up to 4 months before confirming that a person stopped. Clinical response to treatment (defined as a decline in asthma exacerbations of at least 50% compared with the 6 months before starting an asthma biologic) was described over time and in relation to biologic persistence., Results: There were 9575 people who had at least 1 episode of asthma biologic use. There were 5319 people (64%, 95% confidence interval, 63%-65%) who completed 6 months or more on an asthma biologic and 3284 (45%, 95% confidence interval, 44%-46%) who completed 12 months or more. Of people with 1 or more asthma exacerbation 6 months before index biologic use, 63%, 76%, 80%, and 81% realized a 50% or more reduction in postindex asthma exacerbations in the first 6 months, 6 to 12 months, 12 to 18 months, and 18 to 24 months, respectively., Conclusion: Between 48% and 64% of people remained on an asthma biologic for 6 months or more after first use. Most people who achieved a reduction in asthma exacerbations did so in the first 6 months of treatment., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings., Objective: To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes., Design, Setting, and Participants: This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017., Interventions: Two FDA black box warnings released in August 2013 and July 2016., Main Outcomes and Measures: The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2)., Results: The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1., Conclusions and Relevance: This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

Purpose: To compare cardiovascular outcomes and rates of fractures and falls among patients with persistent brand-name versus generic L-thyroxine use., Methods: Retrospective, 1:1 propensity-matched longitudinal study using a national administrative claims database to examine adults (≥18 years) who initiated either brand or generic L-thyroxine between 2008 and 2018, censored at switch or discontinuation of L-thyroxine formulation or disenrollment from the health plan. Main outcome measures included rates of hospitalization for atrial fibrillation, myocardial infarction, congestive heart failure, stroke, spine and hip fractures, and rate of falls in the outpatient or inpatient setting. Hospitalizations for pneumonia were used as a negative control., Results: 195,046 adults initiated treatment with L-thyroxine between 2008 and 2017: 87% generic and 13% brand formulations. They were mostly women (76%), young (94.6% under age 65), white (66%), and 47% had baseline thyroid stimulating hormone levels between 4.5 and 9.9 mIU/L. Among 35,667 propensity-matched patients, there were no significant differences between patients treated with brand versus generic L-thyroxine in atrial fibrillation (HR 0.96, 0.58-1.60), myocardial infarction (HR 0.66, 0.39-1.14), congestive heart failure (HR 1.30, 0.78-2.16), stroke (0.72, 0.49-1.06), spine (HR 0.87, 0.38-1.99) and hip fractures (HR 0.86, 0.26-2.82), or fall outcomes (HR 1.02, 0.14-7.32). Hospitalization rates for pneumonia (used as negative control) did not differ between groups (HR 0.85, 0.61-1.19). There were no interactions between brand versus generic L-thyroxine, these outcomes, and thyroid cancer, age, or L-thyroxine dose subgroups., Conclusions: We found no significant differences in cardiovascular outcomes and rates of falls and fractures for patients who filled brand versus generic L-thyroxine., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: The Pediatric Research Equity Act and Best Pharmaceuticals for Children Act are intended to promote the conduct of clinical trials that generate pediatric-specific evidence about drug safety and efficacy. This study assesses the quality of evidence generated through Pediatric Research Equity Act-mandated and Best Pharmaceuticals for Children Act-incentivized clinical trials of hematology/oncology drugs and characterizes subsequent changes in pediatric drug utilization rates., Methods: Trial characteristics (blinding, randomization, and comparator group) were determined for clinical trials that supported pediatric label changes. Using data from OptumLabs ® Data Warehouse, a de-identified administrative claims database, we calculated pediatric utilization rates for each drug. We calculated monthly utilization rates from January 2003 (or from the first month in which data were available) to December 2018., Results: We identified 11 hematology/oncology drugs that underwent pediatric label changes under the Pediatric Research Equity Act Pediatric Research Equity Act and/or Best Pharmaceuticals for Children Act, and we identified 15 trials supporting these changes. Of these trials, 36% (5/14) were randomized, 31% (4/13) were blinded, and 36% (5/14) used a comparator group. A median of 49 children (interquartile range 29.5) received the drug under investigation across these trials. Pediatric label changes were not associated with subsequent changes in pediatric drug utilization. Although some drugs saw increased pediatric use after gaining new pediatric indications, this pattern was not consistently observed. In addition, there was no evidence to suggest that drugs were utilized less frequently after they failed to receive pediatric indications., Conclusions: Clinical trials of hematology/oncology drugs conducted under the Pediatric Research Equity Act Pediatric Research Equity Act and Best Pharmaceuticals for Children Act generally have low methodological rigor, and the resulting label changes are not consistently associated with changes in pediatric utilization. Alternative regulatory strategies and study designs may be necessary to maximize the impact of newly generated knowledge on drug utilization.

Importance: Diabetes management operates under a complex interrelationship between behavioral, social, and economic factors that affect a patient's ability to self-manage and access care., Objective: To examine the association between 2 complementary area-based metrics, area deprivation index (ADI) score and rurality, and optimal diabetes care., Design, Setting, and Participants: This cross-sectional study analyzed the electronic health records of patients who were receiving care at any of the 75 Mayo Clinic or Mayo Clinic Health System primary care practices in Minnesota, Iowa, and Wisconsin in 2019. Participants were adults with diabetes aged 18 to 75 years. All data were abstracted and analyzed between June 1 and November 30, 2020., Main Outcomes and Measures: The primary outcome was the attainment of all 5 components of the D5 metric of optimal diabetes care: glycemic control (hemoglobin A1c <8.0%), blood pressure (BP) control (systolic BP <140 mm Hg and diastolic BP <90 mm Hg), lipid control (use of statin therapy according to recommended guidelines), aspirin use (for patients with ischemic vascular disease), and no tobacco use. The proportion of patients receiving optimal diabetes care was calculated as a function of block group-level ADI score (a composite measure of 17 US Census indicators) and zip code-level rurality (calculated using Rural-Urban Commuting Area codes). Odds of achieving the D5 metric and its components were assessed using logistic regression that was adjusted for demographic characteristics, coronary artery disease history, and primary care team specialty., Results: Among the 31 934 patients included in the study (mean [SD] age, 59 [11.7] years; 17 645 men [55.3%]), 13 138 (41.1%) achieved the D5 metric of optimal diabetes care. Overall, 4090 patients (12.8%) resided in the least deprived quintile (quintile 1) of block groups and 1614 (5.1%) lived in the most deprived quintile (quintile 5), while 9193 patients (28.8%) lived in rural areas and 2299 (7.2%) in highly rural areas. The odds of meeting the D5 metric were lower for individuals residing in quintile 5 vs quintile 1 block groups (odds ratio [OR], 0.72; 95% CI, 0.67-0.78). Patients residing in rural (OR, 0.84; 95% CI, 0.73-0.97) and highly rural (OR, 0.81; 95% CI, 0.72-0.91) zip codes were also less likely to attain the D5 metric compared with those in urban areas., Conclusions and Relevance: This cross-sectional study found that patients living in more deprived and rural areas were significantly less likely to attain high-quality diabetes care compared with those living in less deprived and urban areas. The results call for geographically targeted population health management efforts by health systems, public health agencies, and payers.

Objective: To provide a review of the impact of high deductible health plans (HDHPs) on the utilizations of services required for optimal management of diabetes and subsequent health outcomes., Methods: Systematic literature review of studies published between January 1, 2000, and May 7, 2021, was conducted that examined the impact of HDHP on diabetes monitoring (eg, recommended laboratory and surveillance testing), routine care (eg, ambulatory appointments), medication management (eg, medication initiation, adherence), and acute health care utilization (eg, emergency department visits, hospitalizations, incident complications)., Results: Of the 303 reviewed articles, 8 were relevant. These studies demonstrated that HDHPs lower spending at the expense of reduced high-value diabetes monitoring, routine care, and medication adherence, potentially contributing to the observed increases in acute health care utilization. Additionally, patient out-of-pocket costs for recommended screenings doubled, and total health care expenditures increased by 49.4% for HDHP enrollees compared with enrollees in traditional health plans. Reductions in disease monitoring and routine care and increases in acute health care utilization were greatest in lower-income patients. None of the studies examined the impact of HDHPs on access to diabetes self-management education, technology use, or glycemic control., Conclusion: Although HDHPs reduce some health care utilization and costs, they appear to do so at the expense of limiting high-value care and medication adherence. Policymakers, providers, and payers should be more cognizant of the potential for negative consequences of HDHPs on patients' health., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Competing Interests: TA-O has received speaker fees or served as a consultant or on an advisory board for Janssen, Boehringer Ingelheim, AbbVie, Arena Pharmaceuticals, Takeda, Genentech-Roche, Celgene, and Hollister. SBi has served as a consultant for Bristol Myers Squibb and AbbVie. SBh has served as consultant, received speaker fees, or been on an advisory board of Janssen, Zydus, Takeda, Ferring, Abbott, and Dr Reddy's Pharma. NN has served as a consultant, received speaker honoraria, or is on an advisory board for Janssen, AbbVie, Takeda, Pfizer, Eli Lilly, Daiichii Sankyo, Forefront Collaborative, VRIS, PriMed, ReachMD, and Imdedex. NDS is a consultant to GI on Demand with American College of Gastroenterology and Gastro Girl. PD has served as a consultant or on an advisory board for Janssen, Pfizer, Prometheus Biosciences, Boehringer Ingelheim, AbbVie, Arena Pharmaceuticals, and Scipher Medicine Corporation; PD also received grants from Takeda Pharmaceutical, Arena Pharmaceuticals, Bristol Myers Squibb–Celgene, and Boehringer Ingelheim. SS holds research grants from Biogen, Takeda, Pfizer, Janssen, AbbVie, Tillotts Pharma, Ferring, and Biohit; served on the advisory boards of Takeda, AbbVie, Merck, Ferring, Pharmacocosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene and Tillots Pharma; and has received speaker fees from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Janssen, Merck, Warner Chilcott and Falk Pharma. The authors acknowledge Sharan Khela for creating figure 1 in the appendix.

Although there have been several case reports and simulation models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission associated with air travel, there are limited data to guide testing strategy to minimize the risk of SARS-CoV-2 exposure and transmission onboard commercial aircraft. Among 9853 passengers with a negative SARS-CoV-2 polymerase chain reaction test performed within 72 hours of departure from December 2020 through May 2021, five (0.05%) passengers with active SARS-CoV-2 infection were identified with rapid antigen tests and confirmed with rapid molecular test performed before and after an international flight from the United States to Italy. This translates to a case detection rate of 1 per 1970 travelers during a time of high prevalence of active infection in the United States. A negative molecular test for SARS-CoV-2 within 72 hours of international airline departure results in a low probability of active infection identified on antigen testing during commercial airline flight., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite coronavirus disease-19 (COVID-19) being a major health crisis in the current times, only a few studies have addressed its potential direct effect on mental health, especially among COVID-19 patients., Aims: This study was conducted to assess the mental health of COVID-19 patients., Materials and Methods: In cross sectional study, mental health status of 301 symptomatic and 200 asymptomatic COVID-19 participants was assessed using the General Health Questionnaire-28., Results: Around 8.78% COVID-19 patients were found to be psychologically distressed that was predominantly higher among symptomatic COVID-19 patients. Risk of psychological distress was significantly higher in females, living in nuclear families and having a history of addiction., Conclusions: COVID-19 patients suffer from psychological distress, which needs to be addressed to cope well with this pandemic situation., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Psychiatry.)

Background: Identifying biologic-treated patients with inflammatory bowel diseases (IBDs) at higher risk of serious infections is a priority. We conducted a retrospective cohort study evaluating frailty and risk of serious infections in biologic-treated patients with IBD., Methods: Using an administrative claims database, we identified biologic-treated patients with IBD between 2014 and 2018 with follow-up 1 year before and after treatment initiation. Using a validated claims-based hospital frailty risk scoring system, patients were classified as frail and nonfrail. We compared the risk of serious infections (infections requiring hospitalization) between frail and nonfrail patients using Cox proportional hazard analysis adjusting for age, comorbidities, disease characteristics, health care utilization, use of corticosteroids, immunomodulators, and opiates., Results: We included 5987 biologic-treated patients with IBD (4881 on TNFα antagonists, 1106 on vedolizumab), of whom 2350 (39.3%) were classified as frail; over 7115 person-years of follow-up was included, and 520 patients developed serious infection. Frailty was not associated with increased risk of serious infection (adjusted hazard ratio [aHR], 1.12; 95% CI, 0.93-1.36), whereas advanced age (older than 60 years), high comorbidity burden, corticosteroid use, opiate use, and prior serious infection were associated with increased risk of serious infection. On stratified analysis, frailty was associated with increased risk of serious infections in vedolizumab-treated patients (aHR, 1.69; 95% CI, 1.03-2.79) but not in TNFα antagonist-treated patients (aHR, 1.03; 95% CI, 0.83-1.27)., Conclusions: In biologic-treated patients with IBD, frailty assessed using a claims-based frailty index was not independently associated with increased risk of serious infections. Future studies evaluating objective and biological measures of frailty are warranted to risk-stratify older patients with IBD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver conditions characterized by significant lipid deposition within hepatocytes. As an overarching diagnosis, NAFLD contains a continuum of progressive liver diseases ranging from isolated liver steatosis to necroinflammatory states leading to end-stage liver disease. Nonalcoholic fatty liver and nonalcoholic steatohepatitis are distinguished by their histologic patterns, with the former exhibiting steatosis without fibrosis or inflammation. This important distinction provides clinicians a timeline within the NAFLD staging to target appropriate interventions against modifiable risk factors. NAFLD is likely formed in response to metabolic imbalances that damage the livers adaptive capacity. Metabolic conditions leading to steatosis mirror common cardiovascular risk factors, including dyslipidemia, diabetes mellitus, and obesity. Acknowledging the common risk factors for development and progression of NAFLD, it is unsurprising the first-line management focuses on the treatment of metabolic syndrome with an emphasis on weight reduction in obese populations. The purpose of this review is to provide a detailed summary of the literature as well as outline the current treatment recommendations for patients with NAFLD with a detailed focus on pharmacologic antiobesity interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To describe physicians' variation in de-adopting concurrent statin and fibrate therapy for type 2 diabetic patients following a reversal in clinical evidence., Data Sources: We analyzed 2007-2015 claims data from OptumLabs ® Data Warehouse, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data., Study Design: We modeled fibrate use among Medicare Advantage and commercially insured type 2 diabetic statin users before and after the publication of the ACCORD lipid trial, which found statins and fibrates were no more effective than statins alone in reducing cardiovascular events among type 2 diabetic patients. We modeled fibrate use trends with physician random effects and physician characteristics such as age and specialty., Data Extraction: We identified patient-year-quarters with one year of continuous insurance enrollment, type 2 diabetes diagnoses, and fibrate use. We designated the physician most responsible for patients' diabetes care based on evaluation and management visits and prescriptions of glucose-lowering drugs., Principal Findings: Fibrate use increased by 0.12 percentage points per quarter among commercial patients (95% CI, 0.10 to 0.14) and 0.17 percentage points per quarter among Medicare Advantage patients (95% CI, 0.13 to 0.20) before the trial and then decreased by 0.16 percentage points per quarter among commercial patients (95% CI, -0.18 to -0.15) and 0.05 percentage points per quarter among Medicare Advantage patients (95% CI, -0.06 to -0.03) after the trial. However, 45% of physicians treating commercial patients and 48% of physicians treating Medicare Advantage patients had positive trends in prescribing following the trial. Physicians' characteristics did not explain their variation (pseudo R 2  = 0.000)., Conclusion: On average, physicians decreased fibrate prescribing following the ACCORD lipid trial. However, many physicians increased prescribing following the trial. Observable physician characteristics did not explain variations in prescribing. Future research should examine whether physicians vary similarly in other de-adoption settings., (© 2021 Health Research and Educational Trust.)

Abstract: Factors impacting the accuracy of ultrasound (US) diagnosis of cleft lip (CL) and its subsequent effect on parents are not well understood. Our objectives were to evaluate how the type of CL (complete versus incomplete) and associated cleft palate affect the accuracy of CL's prenatal diagnosis and to evaluate differences between parents' perception of prenatal US in cases of true-positive versus false-negative results. The authors performed a retrospective review of all patients who underwent repair for nonsyndromic CL following prenatal US. Patients were stratified by type of CL and associated cleft palate. Parents were called to determine if their child's CL was diagnosed via US and their perception of the results. Forty-seven children with complete and 40 with incomplete CL responded to phone calls. The presence of a complete CL (P = 0.001) and an associated cleft palate (P = 0.014) were independently associated with an increased likelihood of prenatal diagnosis. Parents who received a true-positive prenatal diagnosis of CL were more satisfied than those who received a false-negative diagnosis (P = 0.0063). True-positives perceived knowing of their child's diagnosis in advance to be more helpful than false-negatives believed it would have been. These results afford an improved context to interpret US studies and help physicians provide more informed prenatal counseling., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

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.

Objective: The study sought to conduct an informatics analysis on the National Evaluation System for Health Technology Coordinating Center test case of cardiac ablation catheters and to demonstrate the role of informatics approaches in the feasibility assessment of capturing real-world data using unique device identifiers (UDIs) that are fit for purpose for label extensions for 2 cardiac ablation catheters from the electronic health records and other health information technology systems in a multicenter evaluation., Materials and Methods: We focused on data capture and transformation and data quality maturity model specified in the National Evaluation System for Health Technology Coordinating Center data quality framework. The informatics analysis included 4 elements: the use of UDIs for identifying device exposure data, the use of standardized codes for defining computable phenotypes, the use of natural language processing for capturing unstructured data elements from clinical data systems, and the use of common data models for standardizing data collection and analyses., Results: We found that, with the UDI implementation at 3 health systems, the target device exposure data could be effectively identified, particularly for brand-specific devices. Computable phenotypes for study outcomes could be defined using codes; however, ablation registries, natural language processing tools, and chart reviews were required for validating data quality of the phenotypes. The common data model implementation status varied across sites. The maturity level of the key informatics technologies was highly aligned with the data quality maturity model., Conclusions: We demonstrated that the informatics approaches can be feasibly used to capture safety and effectiveness outcomes in real-world data for use in medical device studies supporting label extensions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Importance: Hyperglycemic crises (ie, diabetic ketoacidosis [DKA] and hyperglycemic hyperosmolar state [HHS]) are life-threatening acute complications of diabetes. Efforts to prevent these events at the population level have been hindered by scarce granular data and difficulty in identifying individuals at highest risk., Objective: To assess sociodemographic, clinical, and treatment-related factors associated with hyperglycemic crises in adults with type 1 or type 2 diabetes in the US from 2014 to 2020., Design, Setting, and Participants: This retrospective cohort study analyzed administrative claims and laboratory results for adults (aged ≥18 years) with type 1 or type 2 diabetes from the OptumLabs Data Warehouse from January 1, 2014, through December 31, 2020., Main Outcomes and Measures: Rates of emergency department or hospital visits with a primary diagnosis of DKA or HHS (adjusted for age, sex, race/ethnicity, and region, and for year when calculating annualized rates) were calculated separately for patients with type 1 diabetes and type 2 diabetes. The associations of sociodemographic factors (age, sex, race/ethnicity, region, and income), clinical factors (comorbidities), and treatment factors (glucose-lowering medications, hemoglobin A1c) with DKA or HHS in patients with type 1 or type 2 diabetes were assessed using negative binomial regression., Results: Among 20 156 adults with type 1 diabetes (mean [SD] age, 46.6 [16.5] years; 51.2% male; 72.6% White race/ethnicity) and 796 382 with type 2 diabetes (mean [SD] age, 65.6 [11.8] years; 50.3% female; 54.4% White race/ethnicity), adjusted rates of hyperglycemic crises were 52.69 per 1000 person-years (95% CI, 48.26-57.12 per 1000 person-years) for type 1 diabetes and 4.04 per 1000 person-years (95% CI, 3.88-4.21 per 1000 person-years) for type 2 diabetes. In both groups, factors associated with the greatest hyperglycemic crisis risk were low income (≥$200 000 vs <$40 000: type 1 diabetes incidence risk ratio [IRR], 0.61 [95% CI, 0.46-0.81]; type 2 diabetes IRR, 0.69 [95% CI, 0.56-0.86]), Black race/ethnicity (vs White race/ethnicity: type 1 diabetes IRR, 1.33 [95% CI, 1.01-1.74]; type 2 diabetes IRR, 1.18 [95% CI, 1.09-1.27]), high hemoglobin A1c level (≥10% vs 6.5%-6.9%: type 1 diabetes IRR, 7.81 [95% CI, 5.78-10.54]; type 2 diabetes IRR, 7.06 [95% CI, 6.26-7.96]), history of hyperglycemic crises (type 1 diabetes IRR, 7.88 [95% CI, 6.06-9.99]; type 2 diabetes IRR, 17.51 [95% CI, 15.07-20.34]), severe hypoglycemia (type 1 diabetes IRR, 2.77 [95% CI, 2.15-3.56]; type 2 diabetes IRR, 4.18 [95% CI, 3.58-4.87]), depression (type 1 diabetes IRR, 1.62 [95% CI, 1.37-1.92]; type 2 diabetes IRR, 1.46 [95% CI, 1.34-1.59]), neuropathy (type 1 diabetes IRR, 1.64 [95% CI, 1.39-1.93]; type 2 diabetes IRR, 1.25 [95% CI, 1.17-1.34]), and nephropathy (type 1 diabetes IRR, 1.22 [95% CI, 1.01-1.48]; type 2 diabetes IRR, 1.23 [95% CI, 1.14-1.33]). Age had a U-shaped association with hyperglycemic crisis risk in patients with type 1 diabetes (compared with patients aged 18-44 years: 45-64 years IRR, 0.72 [95% CI, 0.59-0.87]; 65-74 years IRR, 0.62 [95% CI, 0.47-0.80]; ≥75 years IRR, 0.96 [95% CI, 0.66-1.38]). In type 2 diabetes, risk of hyperglycemic crises decreased progressively with age (45-64 years IRR, 0.57 [95% CI, 0.51-0.63]; 65-74 years IRR, 0.44 [95% CI, .39-0.49]; ≥75 years IRR, 0.41 [95% CI, 0.36-0.47]). In patients with type 2 diabetes, higher risk was associated with sodium-glucose cotransporter 2 inhibitor therapy (IRR, 1.30; 95% CI, 1.14-1.49) and insulin dependency (compared with regimens with bolus insulin: regimens with basal insulin only, IRR, 0.69 [95% CI, 0.63-0.75]; and without any insulin, IRR, 0.36 [95% CI, 0.33-0.40])., Conclusions and Relevance: In this cohort study, younger age, Black race/ethnicity, low income, and poor glycemic control were associated with an increased risk of hyperglycemic crises. The findings suggest that multidisciplinary interventions focusing on groups at high risk for hyperglycemic crises are needed to prevent these dangerous events.

Background: Variation in de-adoption of ineffective or unsafe treatments is not well-understood. We examined de-adoption of erythropoiesis-stimulating agents (ESA) in anemia treatment among patients with chronic kidney disease (CKD) following new clinical evidence of harm and ineffectiveness (the TREAT trial) and the FDA's revision of its safety warning., Method: We used a segmented regression approach to estimate changes in use of epoetin alfa (EPO) and darbepoetin alfa (DPO) in the commercial, Medicare Advantage (MA) and Medicare fee-for-service (FFS) populations. We also examined how changes in both trends and levels of use were associated with physicians' characteristics., Results: Use of DPO and EPO declined over the study period. There were no consistent changes in DPO trend across insurance groups, but the level of DPO use decreased right after the FDA revision in all groups. The decline in EPO use trend was faster after the TREAT trial for all groups. Nephrologists were largely more responsive to evidence than primary care physicians. Differences by physician's gender, and age were not consistent across insurance populations and types of ESA., Conclusions: Physician specialty has a dominant role in prescribing decision, and that specializations with higher use of treatment (nephrologists) were more responsive to new evidence of unsafety and ineffectiveness., (© 2021. The Author(s).)

Objective: To examine whether glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are preferentially initiated among patients with cardiovascular disease, heart failure (HF), or nephropathy, where these drug classes have established benefit, compared with dipeptidyl peptidase 4 inhibitors (DPP-4i), for which corresponding benefits have not been demonstrated., Research Design and Methods: We retrospectively analyzed claims of adults with type 2 diabetes included in OptumLabs Data Warehouse, a deidentified database of commercially insured and Medicare Advantage beneficiaries, who first started GLP-1RA, SGLT2i, or DPP-4i therapy between 2016 and 2019. Using multinomial logistic regression, we examined the relative risk ratios (RRR) of starting GLP-1RA and SGLT2i compared with DPP-4i for those with a history of myocardial infarction (MI), cerebrovascular disease, HF, and nephropathy after adjusting for demographic and other clinical factors., Results: We identified 75,395 patients who started GLP-1RA, 58,234 who started SGLT2i, and 91,884 who started DPP-4i. Patients with prior MI, cerebrovascular disease, or nephropathy were less likely to start GLP-1RA rather than DPP-4i compared with patients without these conditions (RRR 0.83 [95% CI 0.78-0.88] for MI, RRR 0.77 [0.74-0.81] for cerebrovascular disease, and RRR 0.87 [0.84-0.91] for nephropathy). Patients with HF or nephropathy were less likely to start SGLT2i (RRR 0.83 [0.80-0.87] for HF and RRR 0.57 [0.55-0.60] for nephropathy). Both medication classes were less likely to be started by non-White and older patients., Conclusions: Patients with cardiovascular disease, HF, and nephropathy, for whom evidence suggests a greater likelihood of benefiting from GLP-1RA and/or SGLT2i therapy, were less likely to start these drugs. Addressing this treatment/benefit paradox, which was most pronounced in non-White and older patients, may help reduce the morbidity associated with these conditions., (© 2021 by the American Diabetes Association.)

Background: Leaders play a crucial role in implementing and sustaining changes in clinical practice, yet there is limited evidence on the strategies to engage them in team problem solving and communication., Objective: Examine the impact of an intervention focused on facilitating leadership during daily huddles on optimizing team-based care and improving outcomes., Design: Cluster-randomized trial using intention-to-treat analysis to measure the effects of the intervention (n = 13 teams) compared with routine practice (n = 16 teams)., Participants: Twenty-nine primary care clinics affiliated with a large integrated health system in the upper Midwest; representing differing practice types and geographic settings., Intervention: Full-day leadership training retreat for team leaders to facilitate of care team huddles. Biweekly coaching calls and two site visits with an assigned coach., Main Measures: Primary outcomes of team development and function were collected, pre- and post-intervention using surveys. Patient satisfaction and quality outcomes were compared pre- and post-intervention as secondary outcomes. Leadership engagement and adherence to the intervention were also assessed., Key Results: A total of 279 pre-intervention and 272 post-intervention surveys were completed. We found no impact on team development (- 0.98, 95% CI (- 3.18, 1.22)), improved team credibility (0.18, 95% CI (0.00, 0.35)), but worse psychological safety (- 0.19, 95% CI (- 0.38, 0.00)). No differences were observed in patient satisfaction; however, results were mixed among quality outcomes. Post hoc analysis within the intervention group showed higher adherence to the intervention was associated with improvement in team coordination (0.47, 95% CI (0.18, 0.76)), credibility (0.28, 95% CI (0.02, 0.53)), team learning (0.42, 95% CI (0.10, 0.74)), and knowledge creation (0.74, 95% CI (0.35, 1.13)) compared to teams that were less engaged., Conclusions: Results of this evaluation showed that leadership training and facilitation were not associated with better team functioning. Additional components to the intervention tested may be necessary to enhance team functioning., Trial Registration: Clinicaltrials.gov Identifier NCT03062670. Registration Date: February 23, 2017. URL: https://clinicaltrials.gov/ct2/show/NCT03062670., (© 2021. Society of General Internal Medicine.)

The term telehealth is often used interchangeably with telemedicine. Telemedicine involves the electronic exchange of medical information between two remote sites for the optimization of patient care, whereas telehealth is the application of all electronic communication and delivery systems in the provision of healthcare. Telehealth gives patients an opportunity to communicate with their healthcare providers and, overall, access ambulatory care that otherwise is not available in their area of residence. Several telehealth delivery systems are available for electronic communication. Telehealth and other communications technologies used in the delivery of healthcare services are regulated at both the federal and state levels. Coverage and payment policies vary among the different insurers (e.g., Medicare, Medicaid, and private plans), and policies may further be defined by state telehealth parity laws. Telenutrition involves the use of digital technology to provide nutrition care to patients and caregivers and shows potential to optimize nutrition care and outcomes. The coronavirus disease 2019 pandemic has contributed to sweeping legislative and regulatory changes that allowed the temporary expansion of telehealth delivery and reimbursement to maintain continuity of care for patients who were not able to come in for an in-person office visit with their healthcare provider. The purpose of this review is to introduce key concepts of telehealth delivery systems including policy, legal, and regulatory considerations for ambulatory care as well as the role of telenutrition in nutrition care, and highlight the evolving role of telehealth in optimizing patient and nutrition care during a pandemic and beyond., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Background: Idiopathic Pulmonary Fibrosis is a chronic, progressive interstitial lung disease for which there is no cure. However, lung function decline, hospitalizations, and mortality may be reduced with the use of the antifibrotic medications, nintedanib and pirfenidone. Historical outcomes for hospitalized patients with Idiopathic Pulmonary Fibrosis are grim; however there is a paucity of data since the approval of nintedanib and pirfenidone for treatment. In this study, we aimed to determine the effect of nintedanib and pirfenidone on mortality following respiratory-related hospitalizations, intensive care unit (ICU) admission, and mechanical ventilation., Methods: Using a large U.S. insurance database, we created a one-to-one propensity score matched cohort of patients with idiopathic pulmonary fibrosis treated and untreated with an antifibrotic who underwent respiratory-related hospitalization between January 1, 2015 and December 31, 2018. Mortality was evaluated at 30 days and end of follow-up (up to 2 years). Subgroup analyses were performed for all patients receiving treatment in an ICU and those receiving invasive and non-invasive mechanical ventilation during the index hospitalization., Results: Antifibrotics were not observed to effect utilization of mechanical ventilation or ICU treatment during the index admission or effect mortality at 30-days. If patients survived hospitalization, mortality was reduced in the treated cohort compared to the untreated cohort when followed up to two years (20.1% vs 47.8%)., Conclusions: Treatment with antifibrotic medications does not appear to directly improve 30-day mortality during or after respiratory-related hospitalizations. Post-hospital discharge, however, ongoing antifibrotic treatment was associated with improved long-term survival., (© 2021. The Author(s).)

Introduction: Obesity has been associated with adverse disease-related outcomes and inferior treatment response to biologic agents in patients with inflammatory bowel diseases (IBDs), but its impact on the risk of treatment-related complications is unknown. We performed a cohort study examining the association between obesity and risk of serious infections in biologic-treated patients with IBD., Methods: Using an administrative claims database, in a cohort of biologic-treated patients with IBD between 2014 and 2018 with follow-up 1 year before and after treatment initiation, we compared the risk of serious infections (infections requiring hospitalization) between obese vs nonobese patients (based on validated administrative claims) using Cox proportional hazard analysis., Results: We included 5,987 biologic-treated patients with IBD (4,881 on tumor necrosis factor-α antagonists and 1,106 on vedolizumab), of whom 524 (8.8%) were classified as obese. Of the 7,115 person-year follow-up, 520 patients developed serious infection. Risk of serious infection was comparable in obese vs nonobese patients (8.8% vs 8.5%; unadjusted hazard ratio, 1.15; 95% confidence interval, 0.86-1.54). After adjusting for age, comorbidities, disease characteristics, health care utilization, use of corticosteroids, immunomodulators, and opiates, obesity was not associated with an increased risk of serious infection (adjusted hazard ratio, 0.74 [95% confidence interval, 0.55-1.01]). Similar results were seen on stratified analysis by disease phenotype (Crohn's disease and ulcerative colitis) and index biologic therapy (tumor necrosis factor-α antagonists and vedolizumab)., Discussion: After adjusting for comorbid conditions and disease characteristics, obesity is not independently associated with an increased risk of serious infections in biologic-treated patients with IBD., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Personal digital devices may offer insights into patient recovery and an approach for remote monitoring after procedures., Objective: To examine associations between activity measured using personal digital devices, patient-reported outcome measures (PROMs), and clinical events among patients after catheter ablation for atrial fibrillation (AF) or bariatric surgery., Methods: We aggregated personal digital device, PROM, and electronic health record data in a study conducted at 2 health systems. We used Fitbit devices for step count assessments, KardiaMobile for cardiac rhythm assessments, and PROMs for pain and palpitations over 5 weeks., Results: Among 59 patients, 30 underwent AF ablation and 29 bariatric surgery. Thirty-six patients (63%) reported pain. There was no difference in median [interquartile range] daily steps between patients with and those without pain (4419 [3286-7041] vs 3498 [2609-5888]; P = .23). Among AF ablation patients, 21 (70%) reported palpitations. Median daily steps were lower among those with palpitations than among those without (4668 [3021-6116] vs 8040 [6853-10,394]; P = .03). When accounting for within-subject correlation, recordings of AF were associated with a significant mean decrease in median daily steps (-351; 95% confidence interval -524 to -177; P <.01). Patients who received a new antiarrhythmic drug prescription had AF recorded in a median of 5 [5-5] of 5 total weeks, whereas patients who did not receive a new antiarrhythmic recorded AF in a median of 1 [0-3] week ( P  = .02)., Conclusion: Personal digital device and PROM data can provide insight into postprocedural recovery outside of usual clinical settings and may inform follow-up and clinical decision-making. (ClinicalTrials.gov Identifier: NCT03436082).

Background: Poor sleep quality harms the ability to think, lowers stress, and sustains a healthy immune system. The present study assessed sleep quality and its determinants in adult population using discriminant function analysis (DFA) in Ahmedabad city, Gujarat., Objectives: The objective of the study was (1) to assess the quality of sleep using the Pittsburgh Sleep Quality Index (PSQI) and (2) to determine various parameters affecting sleep quality using DFA., Materials and Methods: A cross-sectional study was conducted among the general adult population (18-60 years) residing at Ahmedabad city during July-December 2019. The interviewers conducted house-to-house visit among selected households for filling up the predesigned and pretested questionnaire., Results: Out of 600 participants, the mean age of participants was 37.8 ± 18.3 years. As per PSQI, overall sleep quality was poor among 31% of participants. Sleep quality was significantly associated with gender, education, occupation, social class, body mass index, Internet addiction, depression, and spirituality., Conclusion: Overall sleep quality was poor among the study participants. This article considered analysis of determinants of sleep quality among the urban adult population., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Community Medicine.)

Background: The COVID-19 pandemic has led to the risk of common mental illnesses. Consultation liaison psychiatry has been one of the most requested services in the face of this pandemic. We aimed to assess (a) the prevalence of psychiatric illness, (b) different types of psychiatric diagnoses, (c) presenting complaints, (d) reasons for psychiatric referrals, and (e) psychiatric intervention done on COVID-19 positive inpatients referred to consultation liaison psychiatry at tertiary care hospital., Method: This was a retrospective study of data collected from April 1, 2020, to September 15, 2020. Total 300 patients were referred and diagnosed with clinical interview and Diagnostic and Statistical Manual for Mental Disorder Fifth Edition criteria. Analysis was done using chi-square test, Kruskal-Wallis test, and fisher exact test., Results: Out of 300 patients, 26.7% had no psychiatric illness. Adjustment disorder was the commonest psychiatric diagnosis (43%), followed by delirium (10%). Statistically significant differences were found for parameters like Indian Council of Medical Research Category 4 of the patient, (hospitalized severe acute respiratory infection) (P value < 0.001), medical comorbidity (P value = 0.023), and past history of psychiatric consultation (Fisher exact test statistic value <0.001). Behavioral problem (27.6%) was the commonest reason for psychiatric referral. Worrying thoughts (23.3%) was the most frequent complaint. A total of 192 (64.3%) patients were offered pharmacotherapy., Conclusions: Psychiatric morbidity was quite high (73.3%) among them and adjustment disorder was the commonest (43%) psychiatric diagnosis followed by delirium (10%). Pharmacotherapy was prescribed to 64.3% patients and psychosocial management was offered to most of the referred patients., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 Indian Psychiatric Society - South Zonal Branch.)

Predictive models have played a critical role in local, national, and international response to the COVID-19 pandemic. In the United States, health care systems and governmental agencies have relied on several models, such as the Institute for Health Metrics and Evaluation, Youyang Gu (YYG), Massachusetts Institute of Technology, and Centers for Disease Control and Prevention ensemble, to predict short- and long-term trends in disease activity. The Mayo Clinic Bayesian SIR model, recently made publicly available, has informed Mayo Clinic practice leadership at all sites across the United States and has been shared with Minnesota governmental leadership to help inform critical decisions during the past year. One key to the accuracy of the Mayo Clinic model is its ability to adapt to the constantly changing dynamics of the pandemic and uncertainties of human behavior, such as changes in the rate of contact among the population over time and by geographic location and now new virus variants. The Mayo Clinic model can also be used to forecast COVID-19 trends in different hypothetical worlds in which no vaccine is available, vaccinations are no longer being accepted from this point forward, and 75% of the population is already vaccinated. Surveys indicate that half of American adults are hesitant to receive a COVID-19 vaccine, and lack of understanding of the benefits of vaccination is an important barrier to use. The focus of this paper is to illustrate the stark contrast between these 3 scenarios and to demonstrate, mathematically, the benefit of high vaccine uptake on the future course of the pandemic., (Copyright © 2021. Published by Elsevier Inc.)

Rationale: In October 2014, the antifibrotic medications pirfenidone and nintedanib became the first medications approved by the U.S. Food and Drug Administration for use in patients with idiopathic pulmonary fibrosis (IPF). Since approval, there has been no nonregistry analysis of the real-world adoption of these medications in everyday clinical practice. Objectives: To evaluate the adoption, persistence, and out-of-pocket (OOP) costs of pirfenidone and nintedanib since their approval in the United States in 2014. Methods: A retrospective cohort analysis was performed by identifying privately insured and Medicare Advantage beneficiaries with IPF. We then split the patients into three cohorts: those who were untreated and those who filled a prescription for either pirfenidone or nintedanib between October 1, 2014, and July 31, 2019. The primary outcome was adoption of the medications. Secondary outcomes included medication persistence and prescription drug costs. Results: A total of 10,996 patients with IPF were identified in the data set. A minority of patients (26.4%) with IPF identified in the cohort had started either medication since approval in 2014, with the adoption of both medications being comparable at around 13.2%. Those receiving the medications were younger (72 vs. 73.9 yr; P  < 0.0001) and healthier (3.9 vs. 4.9 comorbidities; P  < 0.0001) than those not receiving treatment. Men were significantly more likely to receive treatment than woman (30.0% vs. 21.9%; P  < 0.0001). Among treated patients, 42.8% discontinued the medications during the study period. Patients' OOP expenses per month were high for both drugs (mean, $397.51 for nintedanib; mean, $394.49 for pirfenidone). Conclusions: The adoption of both the antifibrotic medications in the United States in everyday practice has been low since approval and may be associated with the high OOP cost.

Importance: How patients with atrial fibrillation (AF) and their clinicians consider cost in forming care plans remains unknown., Objective: To identify factors that inform conversations regarding costs of anticoagulants for treatment of AF between patients and clinicians and outcomes associated with these conversations., Design, Setting, and Participants: This cohort study of recorded encounters and participant surveys at 5 US medical centers (including academic, community, and safety-net centers) from the SDM4AFib randomized trial compared standard AF care with and without use of a shared decision-making (SDM) tool. Included patients were considering anticoagulation treatment and were recruited by their clinicians between January 30, 2017, and June 27, 2019. Data were analyzed between August and November 2019., Main Outcomes and Measures: The incidence of and factors associated with cost conversations, and the association of cost conversations with patients' consideration of treatment cost burden and their choice of anticoagulation., Results: A total of 830 encounters (out of 922 enrolled participants) were recorded. Patients' mean (SD) age was 71.0 (10.4) years; 511 patients (61.6%) were men, 704 (86.0%) were White, 303 (40.9%) earned between $40 000 and $99 999 in annual income, and 657 (79.2%) were receiving anticoagulants. Clinicians' mean (SD) age was 44.8 (13.2) years; 75 clinicians (53.2%) were men, and 111 (76%) practiced as physicians, with approximately half (69 [48.9%]) specializing in either internal medicine or cardiology. Cost conversations occurred in 639 encounters (77.0%) and were more likely in the SDM arm (378 [90%] vs 261 [64%]; OR, 9.69; 95% CI, 5.77-16.29). In multivariable analysis, cost conversations were more likely to occur with female clinicians (66 [47%]; OR, 2.85; 95% CI, 1.21-6.71); consultants vs in-training clinicians (113 [75%]; OR, 4.0; 95% CI, 1.4-11.1); clinicians practicing family medicine (24 [16%]; OR, 12.12; 95% CI, 2.75-53.38]), internal medicine (35 [23%]; OR, 3.82; 95% CI, 1.25-11.70), or other clinicians (21 [14%]; OR, 4.90; 95% CI, 1.32-18.16) when compared with cardiologists; and for patients with an annual household income between $40 000 and $99 999 (249 [82.2%]; OR, 1.86; 95% CI, 1.05-3.29) compared with income below $40 000 or above $99 999. More patients who had cost conversations reported cost as a factor in their decision (244 [89.1%] vs 327 [69.0%]; OR 3.66; 95% CI, 2.43-5.50), but cost conversations were not associated with the choice of anticoagulation agent., Conclusions and Relevance: Cost conversations were common, particularly for middle-income patients and with female and consultant-level primary care clinicians, as well as in encounters using an SDM tool; they were associated with patients' consideration of treatment cost burden but not final treatment choice. With increasing costs of care passed on to patients, these findings can inform efforts to promote cost conversations in practice., Trial Registration: ClinicalTrials.gov Identifier: NCT02905032.

Background: There is limited information about outcomes associated with stopping asthma biologics., Objective: To compare outcomes in people who stopped or continued asthma biologics., Methods: We identified a cohort of people with asthma who stopped or continued asthma biologics in the Optum Labs Database Warehouse, using a propensity matching method for case and control groups with the variables of age, sex, race, region, insurance, income, specialist access, Charlson comorbidity, specific medical conditions, pre-index exacerbation count, pre-index rescue inhaler pharmacy fills, and pre-index inhaled corticosteroid with or without long-acting β-agonist pharmacy fills. Primary outcome used to assess failure of stopping was an increase of 50% or more in the asthma exacerbation rate in the 6 months after discontinuing the biologic compared with the 6-month period before biologic initiation., Results: Among a cohort of 4960 asthma biologic users, 1249 were observed to stop use after 6 to 12 months of use. We identified a matched cohort of 1247 stoppers and 1247 people who continued biologic use for at least 18 months. In the first 6 months after stopping or sham stopping, 10.2% of stoppers and 9.5% of continuers had an increase of 50% or more in asthma exacerbations. We found a similar adjusted odds of failing among stoppers and continuers (odds ratio = 1.085; 95% confidence interval, 0.833-1.413)., Conclusions: An increase in asthma exacerbations is infrequently observed in people who stopped asthma biologics and was observed at similar rates as in matched controls who continued asthma biologics., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Aims: This study aims to evaluate the impact of the combination of cardiogenic shock (CS) and cardiac arrest (CA) complicating non-ST-segment elevation myocardial infarction (NSTEMI)., Methods and Results: Adult (>18 years) NSTEMI admissions using the National Inpatient Sample database (2000 to 2017) were stratified by the presence of CA and/or CS. Outcomes of interest included in-hospital mortality, early coronary angiography, hospitalization costs, and length of stay. Of the 7 302 447 hospitalizations due to NSTEMI, 147 795 (2.0%) had CS only, 155 522 (2.1%) had CA only, and 41 360 (0.6%) had both CS and CA. Compared with 2000, the adjusted odds ratios (ORs) and 95% confidence interval (CIs) for CS, CA, and both CS and CA in 2017 were 3.75 (3.58-3.92), 1.46 (1.42-1.50), and 4.52 (4.16-4.87), respectively (all P < 0.001). The CS + CA (61.2%) cohort had higher multiorgan failure than CS (42.3%) and CA only (32.0%) cohorts, P < 0.001. The CA only cohort had lower rates of overall (52% vs. 59-60%) and early (17% vs. 18-27%) angiography compared with the other groups (all P < 0.001). CS + CA admissions had higher in-hospital mortality compared with those with CS alone (aOR 4.12 [95% CI 4.00-4.24]), CA alone (aOR 1.69 [95% CI 1.65-1.74]), or without CS/CA (aOR 22.66 [95% CI 22.06-23.27]). The presence of CS, either alone or with CA, was associated with higher hospitalization costs and longer hospital length of stay., Conclusions: The combination of CS and CA is associated with higher rates of acute non-cardiac organ failure and in-hospital mortality in NSTEMI admissions as compared with those with either CS or CA alone., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Importance: After US Food and Drug Administration (FDA) approval of a new drug, sponsors can submit additional clinical data to obtain supplemental approval for use for new indications., Objective: To characterize pivotal trials supporting recent supplemental new indication approvals of drugs and biologics by the FDA and to compare them with pivotal trials that supported these therapeutics' original indication approvals., Design, Setting, and Participants: This is a cross-sectional study characterizing pivotal trials supporting supplemental indication approvals by the FDA between 2017 and 2019 and pivotal trials that supported these therapeutics' original indication approvals. Data analysis was performed from August to October 2020., Main Outcomes and Measures: Number and design of pivotal trials supporting both supplemental and original indication approvals., Results: From 2017 to 2019, the FDA approved 146 supplemental indications for 107 therapeutics on the basis of 181 pivotal efficacy trials. The median (interquartile range) number of trials per supplemental indication was 1 (1-1). Most trials used either placebo (77 trials [42.5%; 95% CI, 35.6%-49.8%]) or active comparators (65 trials [35.9%; 95% CI, 29.3%-43.1%]), and most of these multigroup trials were randomized (141 trials [99.3%; 95% CI, 96.0%-100.0%]) and double-blinded (106 trials [74.5%; 95% CI, 66.6%-81.0%]); 80 trials (44.2%; 95 CI, 37.2%-51.5%) used clinical outcomes as the primary efficacy end point. There was no difference between oncology therapies and those approved for other therapeutic areas to have supplemental indication approvals be based on at least 2 pivotal trials (11.5% vs 20.6%; difference, 9.1%; 95% CI, 2.9%-21.0%; P = .10). Similarly, there was no difference in use of randomization (98.3% vs 100.0%; difference, 1.7%; 95% CI, 1.6%-5.0%; P = .43) among multigroup trials, although these trials were less likely to be double-blinded (50.8% vs 92.3%; difference, 41.5%; 95% CI, 27.4%-55.5%; P < .001); overall, these trials were less likely to use either placebo or active comparators (64.9% vs 86.7%; difference, 21.8% 95% CI, 9.8%-33.9%; P < .001) or to use clinical outcomes as their primary efficacy end point (27.5% vs 61.1%; difference, 33.6%; 95% CI, 14.1%-40.9%; P < .001) and were longer (median [interquartile range], 17 [6-48] weeks vs 95 [39-146] weeks). Original approvals were more likely than supplemental indication approvals to be based on at least 2 pivotal trials (44.0% [95% CI, 33.7%-42.6%] vs 15.8% [95% CI, 10.7%-22.5%]; difference, 28.2%; 95% CI, 17.6%-39.6%; P < .001) and less likely to be supported by at least 1 trial of 12 months' duration (27.6% [95% CI, 17.9%-35.0%] vs 54.8% [95% CI, 46.7%-62.6%]; difference, 27.2%; 95% CI, 14.5%-37.8%; P < .001). Pivotal trial designs were otherwise not significantly different., Conclusions and Relevance: These findings suggest that the number and design of the pivotal trials supporting supplemental indication approvals by the FDA varied across therapeutic areas, with the strength of evidence for cancer indications weaker than that for other indications. There was little difference in the design characteristics of the pivotal trials supporting supplemental indication and original approvals.