Paternal and Maternal Metformin Use and the Risk for Major Congenital Malformations

Long COVID: The Enduring Pandemic

“Redlining” Maps and Contemporary Firearm Violence Research: Is It Time to Ask New Questions?

A Salty Odyssey: A Potassium-Enriched Journey Inspired by Don Quijote

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.

Cardiovascular Disease Mortality Among Native Hawaiian and Pacific Islander Adults Aged 35 Years or Older, 2018 to 2022

Background: Native Hawaiian and Pacific Islander (NHPI) adults have historically been grouped with Asian adults in U.S. mortality surveillance. Starting in 2018, the 1997 race and ethnicity standards from the U.S. Office of Management and Budget were adopted by all states on death certificates, enabling national-level estimates of cardiovascular disease (CVD) mortality for NHPI adults independent of Asian adults. Objective: To describe CVD mortality among NHPI adults. Design: Race-stratified age-standardized mortality rates (ASMRs) and rate ratios were calculated using final mortality data from the National Vital Statistics System for 2018 to 2022. Setting: Fifty states and the District of Columbia. Participants: Adults aged 35 years or older at the time of death. Measurements: CVD deaths were identified from International Classification of Diseases, 10th Revision codes indicating CVD (I00 to I99) as the underlying cause of death. Results: From 2018 to 2022, 10 870 CVD deaths (72.6% from heart disease; 19.0% from cerebrovascular disease) occurred among NHPI adults. The CVD ASMR for NHPI adults (369.6 deaths per 100 000 persons [95% CI, 362.4 to 376.7]) was 1.5 times higher than for Asian adults (243.9 deaths per 100 000 persons [CI, 242.6 to 245.2]). The CVD ASMR for NHPI adults was the third highest in the country, after Black adults (558.8 deaths per 100 000 persons [CI, 557.4 to 560.3]) and White adults (423.6 deaths per 100 000 persons [CI, 423.2 to 424.1]). Limitation: Potential misclassification of underlying cause of death or race group. Conclusion: NHPI adults have a high rate of CVD mortality, which was previously masked by aggregation of the NHPI population with the Asian population. The results of this study support the need for continued disaggregation of the NHPI population in public health research and surveillance to identify opportunities for intervention. Primary Funding Source: National Institute of General Medical Sciences, National Institutes of Health.

Development and Evaluation of a Framework for Identifying and Addressing Spin for Harms in Systematic Reviews of Interventions

“Spin” refers to misleading reporting, interpretation, and extrapolation of findings in primary and secondary research (such as in systematic reviews). The study of spin primarily focuses on beneficial outcomes. The objectives of this research were threefold: first, to develop a framework for identifying spin associated with harms in systematic reviews of interventions; second, to apply the framework to a set of reviews, thereby pinpointing instances where spin may be present; and finally, to revise the spin examples, offering guidance on how spin can be rectified. The authors developed their framework through an iterative process that engaged an international group of researchers specializing in spin and reporting bias. The framework comprises 12 specific types of spin for harms, grouped by 7 categories across the 3 domains (reporting, interpretation, and extrapolation). The authors subsequently gathered instances of spin from a random sample of 100 systematic reviews of interventions. Of the 58 reviews that assessed harm and the 42 that did not, they found that 28 (48%) and 6 (14%), respectively, had at least 1 of the 12 types of spin for harms. Inappropriate extrapolation of the results and conclusions for harms to populations, interventions, outcomes, or settings not assessed in a review was the most common category of spin in 17 of 100 reviews. The authors revised the examples to remove spin, taking into consideration the context (for example, medical discipline, source population), findings for harms, and methodological limitations of the original reviews. They provide guidance for authors, peer reviewers, and editors in recognizing and rectifying or (preferably) avoiding spin, ultimately enhancing the clarity and accuracy of harms reporting in systematic review publications.

Colorectal Cancer Screening Completion and Yield in Patients Aged 45 to 50 Years: An Observational Study: Annals of Internal Medicine: Vol 177, No 12

Background: Guidelines now recommend initiating colorectal cancer (CRC) screening at age 45 years rather than 50 years, but little is known about screening completion and yield among people aged 45 to 49 years. Objective: To evaluate fecal immunochemical test (FIT) completion and yield in patients aged 45 to 49 versus 50 years. Design: Retrospective cohort study. Setting: Kaiser Permanente Northern California, Washington, and Colorado. Patients: Those distributed a FIT kit during January to September 2022. Measurements: FIT completion within 3 months, FIT positivity, receipt of colonoscopy within 3 months after a positive FIT result, and colonoscopy yield. Results: A total of 267 732 FIT kits were distributed: 213 928 (79.9%) to patients aged 45 to 49 years, and 53 804 (20.1%) to those aged 50 years. Overall, FIT completion was slightly higher in patients aged 45 to 49 years (38.9% vs. 37.5%; adjusted risk ratio [aRR], 1.05 [95% CI, 1.04 to 1.06]), although at Colorado, those aged 45 to 49 years were substantially less likely to complete a FIT (30.7% vs. 40.2%; aRR, 0.77 [CI, 0.73 to 0.80]). Overall, FIT positivity was lower in patients aged 45 to 49 years (3.6% vs. 4.0%; aRR, 0.91 [CI, 0.84 to 0.98]), and receipt of colonoscopy after a positive FIT result was similar between groups (64.9% vs. 67.4%; aRR, 1.00 [CI, 0.94 to 1.05]). Adenoma detection was lower in the younger group (58.8% vs. 67.7%; aRR, 0.88 [CI, 0.83 to 0.95]). Yields were similar for adenoma with advanced histology (13.2% vs. 15.9%; aRR, 0.86 [CI, 0.69 to 1.07]), polyp with high-grade dysplasia (3.4% vs. 5.1%; aRR, 0.68 [CI, 0.44 to 1.04]), sessile serrated lesion (10.3% vs. 11.7%; aRR, 0.92 [CI, 0.71 to 1.21]), and CRC (2.8% vs. 2.7%; aRR, 1.10 [CI, 0.62 to 1.96]). Limitation: The small number of neoplasia events contributed to wide CIs. Conclusion: Similar FIT completion and yield rates in people aged 45 to 50 years support initiation of CRC screening at age 45 years. Primary Funding Source: Kaiser Permanente Sidney R. Garfield Memorial Fund.

Untangling the Benefits of Time-Restricted Eating: Is It the Calories or the Time Restriction?

Infectious Diseases: What You May Have Missed in 2023

In 2023, published research on COVID-19 remains prominent. The aim of this article is to highlight important developments in infectious disease evidence unrelated to COVID-19 that were published in 2023. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The highlighted publications relate to various organisms and patient populations. One article provides insight into the updated guidelines for the diagnosis and management of infective endocarditis. Several articles address the management of sepsis and bacteremia: comparison of cefepime versus piperacillin–tazobactam, ceftobiprole for the treatment of complicated Staphylococcus aureus bacteremia, and early switch from intravenous to oral antibiotics in patients with gram-negative bacteremia. Another article examines differences in all-cause mortality in patients with Clostridioides difficile infection who receive different treatments. Additional articles provide evidence about the treatment of patients with HIV infection: the utility of preexposure prophylaxis to prevent HIV infection, the efficacy of pitavastatin in reducing cardiovascular disease, and the efficacy of dexamethasone for the treatment of tuberculous meningitis in persons with HIV.