Determining Women’s Willingness to Screen for Breast Cancer: Does False-Positive Recall Matter?

Time-Restricted Eating in Adults With Metabolic Syndrome: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 177, No 11

Background: Time-restricted eating (TRE), limiting daily dietary intake to a consistent 8 to 10 hours without mandating calorie reduction, may provide cardiometabolic benefits. Objective: To determine the effects of TRE as a lifestyle intervention combined with current standard-of-care treatments on cardiometabolic health in adults with metabolic syndrome. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT04057339) Setting: Clinical research institute. Participants: Adults with metabolic syndrome including elevated fasting glucose or hemoglobin A1c (HbA1c; pharmacotherapy allowed). Intervention: Participants were randomly assigned to standard-of-care (SOC) nutritional counseling alone (SOC group) or combined with a personalized 8- to 10-hour TRE intervention (≥4-hour reduction in eating window) (TRE group) for 3 months. Timing of dietary intake was tracked in real time using the myCircadianClock smartphone application. Measurements: Primary outcomes were HbA1c, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycemic assessments from continuous glucose monitors. Results: 108 participants from the TIMET study completed the intervention (89% of those randomly assigned; 56 women, mean baseline age, 59 years; body mass index of 31.22 kg/m2; eating window of 14.19 hours). Compared with SOC, TRE improved HbA1c by −0.10% (95% CI, −0.19% to −0.003%). Statistical outcomes were adjusted for age. There were no major adverse events. Limitation: Short duration, self-reported diet, potential for multiple elements affecting outcomes. Conclusion: Personalized 8- to 10-hour TRE is an effective practical lifestyle intervention that modestly improves glycemic regulation and may have broader benefits for cardiometabolic health in adults with metabolic syndrome on top of SOC pharmacotherapy and nutritional counseling. Primary Funding Source: National Institutes of Health.

Mammography Screening Preferences Among Screening-Eligible Women in Their 40s: A National U.S. Survey: Annals of Internal Medicine: Vol 177, No 8

Background: The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years. Although many women welcome this change, some may prefer not to be screened at age 40 years. Objective: To conduct a national probability-based U.S. survey to investigate breast cancer screening preferences among women aged 39 to 49 years. Design: Pre–post survey with a breast cancer screening decision aid (DA) intervention. (ClinicalTrials.gov: NCT05376241) Setting: Online national U.S. survey. Participants: 495 women aged 39 to 49 years without a history of breast cancer or a known BRCA1/2 gene mutation. Intervention: A mammography screening DA providing information about screening benefits and harms and a personalized breast cancer risk estimate. Measurements: Screening preferences (assessed before and after the DA), 10-year Gail model risk estimate, and whether the information was surprising and different from past messages. Results: Before viewing the DA, 27.0% of participants preferred to delay screening (vs. having mammography at their current age), compared with 38.5% after the DA. There was no increase in the number never wanting mammography (5.4% before the DA vs. 4.3% after the DA). Participants who preferred to delay screening had lower breast cancer risk than those who preferred not to delay. The information about overdiagnosis was surprising for 37.4% of participants versus 27.2% and 22.9% for information about false-positive results and screening benefits, respectively. Limitation: Respondent preferences may have been influenced by the then-current USPSTF guideline. Conclusion: There are women in their 40s who would prefer to have mammography at an older age, especially after being informed of the benefits and harms of screening. Women who wanted to delay screening were at lower breast cancer risk than women who wanted screening at their current age. Many found information about the benefits and harms of mammography surprising. Primary Funding Source: National Cancer Institute.

Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 177, No 5

Background: The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. Objective: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, plazomicin, eravacycline, imipenem–relebactam–cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics). Design: Retrospective cohort. Setting: 619 U.S. hospitals. Participants: Adult inpatients. Measurements: Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections. Results: Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane–tazobactam (approved 2014) and ceftazidime–avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including “reserve” antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage. Limitation: Residual confounding. Conclusion: Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety–efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. Primary Funding Source: U.S. Food and Drug Administration; NIH Intramural Research Program.

Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 177, No 2

Background: Chronic insomnia is common in patients undergoing in-center hemodialysis, yet there is limited evidence on effective treatments for this population. Objective: To compare the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), trazodone, and placebo for insomnia in patients undergoing long-term hemodialysis. Design: Randomized, multicenter, double-blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT03534284) Setting: 26 dialysis units in Albuquerque, New Mexico, and Seattle, Washington. Participants: Patients with Insomnia Severity Index (ISI) score of 10 or greater, with sleep disturbances on 3 or more nights per week for 3 or more months. Intervention: Participants were randomly assigned to 6 weeks of CBT-I, trazodone, or placebo. Measurements: The primary outcome was the ISI score at 7 and 25 weeks from randomization. Results: A total of 923 patients were prescreened, and of the 411 patients with chronic insomnia, 126 were randomly assigned to CBT-I (n = 43), trazodone (n = 42), or placebo (n = 41). The change in ISI scores from baseline to 7 weeks with CBT-I or trazodone was no different from placebo: CBT-I, −3.7 (95% CI, −5.5 to −1.9); trazodone, −4.2 (CI, −5.9 to −2.4); and placebo, −3.1 (CI, −4.9 to −1.3). There was no meaningful change in ISI scores from baseline to 25 weeks: CBT-I, −4.8 (CI, −7.0 to −2.7); trazodone, −4.0 (CI, −6.0 to −1.9); and placebo, −4.3 (CI, −6.4 to −2.2). Serious adverse events (SAEs), particularly serious cardiovascular events, were more frequent with trazodone (annualized cardiovascular SAE incidence rates: CBT-I, 0.05 [CI, 0.00 to 0.29]; trazodone, 0.64 [CI, 0.34 to 1.10]; and placebo, 0.21 [CI, 0.06 to 0.53]). Limitation: Modest sample size and most participants had mild or moderate insomnia. Conclusion: In patients undergoing hemodialysis with mild or moderate chronic insomnia, there was no difference in the effectiveness of 6 weeks of CBT-I or trazodone compared with placebo. The incidence of SAEs was higher with trazodone. Primary Funding Source: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

Atrial Fibrillation Recurrence in Patients With Transient New-Onset Atrial Fibrillation Detected During Hospitalization for Noncardiac Surgery or Medical Illness: A Matched Cohort Study: Annals of Internal Medicine: Vol 176, No 10

Background: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear. Objective: To estimate risk for AF recurrence in patients with new-onset AF during a hospitalization for noncardiac surgery or medical illness compared with a matched population without AF. Design: Matched cohort study. (ClinicalTrials.gov: NCT03221777) Setting: Three academic hospitals in Hamilton, Ontario, Canada. Participants: The study enrolled patients hospitalized for noncardiac surgery or medical illness who had transient new-onset AF. For each participant, an age- and sex-matched control participant with no history of AF from the same hospital ward was recruited. All participants left the hospital in sinus rhythm. Measurements: 14-day electrocardiographic (ECG) monitor at 1 and 6 months and telephone assessment at 1, 6, and 12 months. The primary outcome was AF lasting at least 30 seconds on the monitor or captured by ECG 12-lead during routine care at 12 months. Results: Among 139 participants with transient new-onset AF (70 patients with medical illness and 69 surgical patients) and 139 matched control participants, the mean age was 71 years (SD, 10), the mean CHA2DS2-VASc score was 3.0 (SD, 1.5), and 59% were male. The median duration of AF during the index hospitalization was 15.8 hours (IQR, 6.4 to 49.6 hours). After 1 year, recurrent AF was detected in 33.1% (95% CI, 25.3% to 40.9%) of participants in the transient new-onset AF group and 5.0% (CI, 1.4% to 8.7%) of matched control participants; after adjustment for the number of ECG monitors worn and for baseline clinical differences, the adjusted relative risk was 6.6 (CI, 3.2 to 13.7). After exclusion of participants who had electrical or pharmacologic cardioversion during the index hospitalization (n = 40) and their matched control participants and limiting to AF events detected by the patch ECG monitor, recurrent AF was detected in 32.3% (CI, 23.1% to 41.5%) of participants with transient new-onset AF and 3.0% (CI, 0% to 6.4%) of matched control participants. Limitations: Generalizability is limited, and the study was underpowered to evaluate subgroups and clinical predictors. Conclusion: Among patients who have transient new-onset AF during a hospitalization for noncardiac surgery or medical illness, approximately 1 in 3 will have recurrent AF within 1 year. Primary Funding Source: Peer-reviewed grants.

Perioperative Safety and Early Patient and Device Outcomes Among Subcutaneous Versus Transvenous Implantable Cardioverter Defibrillator Implantations: A Randomized, Multicenter Trial: Annals of Internal Medicine: Vol 175, No 12

Background: Implantable cardioverter defibrillators (ICDs) improve survival in patients at risk for cardiac arrest, but are associated with intravascular lead-related complications. The subcutaneous ICD (S-ICD), with no intravascular components, was developed to minimize lead-related complications. Objective: To assess key ICD performance measures related to delivery of ICD therapy, including inappropriate ICD shocks (delivered in absence of life-threatening arrhythmia) and failed ICD shocks (which did not terminate ventricular arrhythmia). Design: Randomized, multicenter trial. (ClinicalTrials.gov: NCT02881255) Setting: The ATLAS trial. Patients: 544 eligible patients (141 female) with a primary or secondary prevention indication for an ICD who were younger than age 60 years, had a cardiogenetic phenotype, or had prespecified risk factors for lead complications were electrocardiographically screened and 503 randomly assigned to S-ICD (251 patients) or transvenous ICD (TV-ICD) (252 patients). Mean follow-up was 2.5 years (SD, 1.1). Mean age was 49.0 years (SD, 11.5). Measurements: The primary outcome was perioperative major lead-related complications. Results: There was a statistically significant reduction in perioperative, lead-related complications, which occurred in 1 patient (0.4%) with an S-ICD and in 12 patients (4.8%) with TV-ICD (−4.4%; 95% CI, −6.9 to −1.9; P = 0.001). There was a trend for more inappropriate shocks with the S-ICD (hazard ratio [HR], 2.37; 95% CI, 0.98 to 5.77), but no increase in failed appropriate ICD shocks (HR, 0.61 (0.15 to 2.57). Patients in the S-ICD group had more ICD site pain, measured on a 10-point numeric rating scale, on the day of implant (4.2 ± 2.8 vs. 2.9 ± 2.2; P < 0.001) and 1 month later (1.3 ± 1.8 vs. 0.9 ± 1.5; P = 0.035). Limitation: At present, the ATLAS trial is underpowered to detect differences in clinical shock outcomes; however, extended follow-up is ongoing. Conclusion: The S-ICD reduces perioperative, lead-related complications without significantly compromising the effectiveness of ICD shocks, but with more early postoperative pain and a trend for more inappropriate shocks. Primary Funding Source: Boston Scientific.

Would You Recommend a Statin to This Patient for Primary Prevention of Cardiovascular Disease?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 175, No 6

Cardiovascular disease (CVD) is the leading cause of death in the United States. Hypercholesterolemia is a principal modifiable risk factor for the primary prevention of CVD. In addition to lifestyle modification, statins are an important tool to reduce risk for CVD in selected patients. A useful strategy to identify candidates for statins is to estimate the 10-year risk for CVD through the use of a validated risk calculator. Commonly used calculators include the Framingham risk score and the pooled cohort equation. Multiple randomized controlled trials have shown that statins reduce the risk for CVD in patients without known CVD. Two recent guidelines have proposed an approach to the use of statins in primary prevention of CVD. The American College of Cardiology/American Heart Association and the U.S. Department of Veterans Affairs guidelines form the basis for this discussion. The guidelines differ on the use of advanced testing to modify the 10-year CVD risk estimate and on the need for low-density lipoprotein cholesterol targets to establish the efficacy of statins. Advanced testing with coronary artery calcium measurement may be helpful for patients who are potentially eligible for statin therapy but who are uncertain if they wish to take a statin. In this paper, 2 experts, a preventive cardiologist and a general internist, discuss their approach to the use of statins for primary prevention of CVD and how they would apply the guidelines to an individual patient.

Diversity in Internal Medicine Residency Programs: Time to Redesign the Gatekeepers and the Gate

How Would You Treat This Patient With Acute and Chronic Pain From Sickle Cell Disease?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 175, No 4

Sickle cell disease is prevalent in large numbers of patients in the United States and has a significant global impact. Its complications span numerous organs and lead to reduced life expectancy. Acute and chronic sickle cell pain is a common cause of patient suffering. The American Society of Hematology published updated guidelines on management of acute and chronic pain from sickle cell disease in 2019. Several of the recommendations are conditional and leave specific decisions to the treating physician. These include conditional recommendations about the use of ketamine for acute pain and the initiation and discontinuation of long-term opioid therapy for chronic pain. Here, 2 hematologists discuss these guidelines and make contrasting recommendations for the management of acute and chronic pain for a patient with sickle cell disease.