The Effect of Heat Exposure on Myocardial Blood Flow and Cardiovascular Function

Background: Heat extremes are associated with greater risk for cardiovascular death. The pathophysiologic mechanisms mediating this association are unknown. Objective: To quantify the myocardial blood flow (MBF) requirements of heat exposure. Design: Experimental study. (ClinicalTrials.gov: NCT04549974) Setting: Laboratory-based. Participants: 61 participants, comprising 20 healthy young adults (mean age, 28 years), 21 healthy older adults (mean age, 67 years), and 20 older adults with coronary artery disease (CAD) (mean age, 70 years). Intervention: Participants were heated until their core temperature increased 1.5 °C; MBF was measured before heat exposure and at every increase of 0.5 °C in core temperature. Measurements: The primary outcome was MBF measured by positron emission tomography–computed tomography. Secondary outcomes included heart rate, blood pressure, and body weight change. Results: At a core temperature increase of 1.5 °C, MBF increased in healthy young adults (change, 0.8 mL/min/g [95% CI, 0.5 to 1.0 mL/min/g]), healthy older adults (change, 0.7 mL/min/g [CI, 0.5 to 0.9 mL/min/g]), and older adults with CAD (change, 0.6 mL/min/g [CI, 0.3 to 0.8 mL/min/g]). This represented a 2.08-fold (CI, 1.75- to 2.41-fold), 1.79-fold (CI, 1.59- to 1.98-fold), and 1.64-fold (CI, 1.41- to 1.87-fold) change, respectively, from preexposure values. Imaging evidence of asymptomatic heat-induced myocardial ischemia was seen in 7 adults with CAD (35%) in post hoc analyses. Limitations: In this laboratory-based study, heating was limited to about 100 minutes and participants were restricted in movement and fluid intake. Participants refrained from strenuous exercise and smoking; stopped alcohol and caffeine intake; and withheld β-blockers, calcium-channel blockers, and nitroglycerin before heating. Conclusion: Heat exposure that increases core temperature by 1.5 °C nearly doubles MBF. Changes in MBF did not differ by age or presence of CAD, but some older adults with CAD may experience asymptomatic myocardial ischemia. Primary Funding Source: Canadian Institutes of Health Research.

Methotrexate: Borrowed Hope for Persons With Knee Osteoarthritis?

Medicare Advantage: High Costs and Poor Protection

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.

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.

Long COVID Definitions and Models of Care: A Scoping Review: Annals of Internal Medicine: Vol 177, No 7

Background: Definitions of long COVID are evolving, and optimal models of care are uncertain. Purpose: To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models. Data Sources: English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants. Study Selection: Publications describing long COVID definitions or models of care, supplemented by models described by key informants. Data Extraction: Data were extracted by one reviewer and verified for accuracy by another reviewer. Data Synthesis: Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score–based. Forty-nine long COVID care models were informed by 5 key principles: a core “lead” team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified. Limitations: Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models. Conclusion: Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models. Primary Funding Source: Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.)

Nephrology: What You May Have Missed in 2023

This article highlights a selection of important nephrology studies published in 2023 that have relevance for nonnephrologist physicians. Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults.

Cardiology: What You May Have Missed in 2023

Cardiology and all its subspecialties continue to push the envelope in developing new treatment strategies for a wide variety of diseases. After screening more than 1300 articles, we highlight a selection of important cardiology articles published in 2023. Starting with prevention, we note articles that look at the effect of semaglutide in patients with obesity as well as a first-in-class drug, bempedoic acid, on cardiovascular outcomes. We have also examined new evidence comparing conservative management with invasive management of frail, older patients with non–ST-segment elevation myocardial infarction (NSTEMI). In patients with cardiac arrest secondary to NSTEMI, another article examines the rationale for expedited transfer to a cardiac arrest center. The STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) trial builds on looking at half-dose thrombolysis in older populations with STEMI. Emphasis is placed on guideline-directed medical therapy before hospital discharge in those with heart failure. In addition, in patients with stable symptomatic coronary artery disease, initial noninvasive testing using coronary computed tomography angiography may be a viable option compared with invasive strategies. More details have emerged on anticoagulation strategies in those with device-detected atrial fibrillation. Finally, transcatheter approaches to treat both mitral and tricuspid regurgitation have also been included.

Cost-Effectiveness of Extending Human Papillomavirus Vaccination to Population Subgroups Older Than 26 Years Who Are at Higher Risk for Human Papillomavirus Infection in the United States

Background: In June 2019, the U.S. Advisory Committee on Immunization Practices recommended shared clinical decision making regarding potential human papillomavirus (HPV) vaccination of men and women aged 27 to 45 years (“mid-adults”). Objective: To examine the incremental cost-effectiveness ratios (ICERs) and number needed to vaccinate (NNV) to prevent 1 HPV-related cancer case of expanding HPV vaccination to subgroups of mid-adults at increased risk for HPV-related diseases in the United States. Design: Individual-based transmission dynamic modeling of HPV transmission and associated diseases using HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation). Data Sources: Published data. Target Population: All U.S. mid-adults and higher-risk subgroups within this population. Time Horizon: 100 years. Perspective: Health care sector. Intervention: Expanding 9-valent HPV vaccination to mid-adults and higher-risk subgroups. Outcome Measures: ICERs and NNVs. Results of Base-Case Analysis: Expanding 9-valent HPV vaccination to all mid-adults, those with more lifetime partners, and those who have just separated was projected to cost an additional $2 005 000, $763 000, and $1 164 000 per quality-adjusted life-year (QALY) gained, respectively. The NNVs to prevent 1 additional HPV-related cancer case were 7670, 3190, and 5150, respectively, compared with 223 for vaccination of persons aged 9 to 26 years (vs. no vaccination). Results of Sensitivity Analysis: The mid-adult strategy with the lowest ICER and NNV was vaccinating infrequently screened mid-adult women who have just separated and have a higher number of lifetime sex partners (ICER, $86 000 per QALY gained; NNV, 470). Limitation: Uncertainty about rate of new sex partners and natural history of HPV among mid-adults. Conclusion: Vaccination of mid-adults against HPV is substantially less cost-effective and produces higher NNVs than vaccination of persons younger than 26 years under all scenarios investigated. However, cost-effectiveness and NNV are projected to improve when higher-risk mid-adult subgroups are vaccinated, such as mid-adults with more sex partners and who have recently separated, and women who are underscreened. Primary Funding Source: Centers for Disease Control and Prevention.

Viral Load–Based Prediction of Hepatocellular Carcinoma Risk in Noncirrhotic Patients With Chronic Hepatitis B: A Multinational Study for the Development and External Validation of a New Prognostic Model: Annals of Internal Medicine: Vol 177, No 10

Background: A nonlinear association between serum hepatitis B virus (HBV) DNA levels and hepatocellular carcinoma (HCC) risk has been suggested in patients with chronic hepatitis B (CHB). Objective: To develop and externally validate a prognostic model for HCC risk in noncirrhotic adult patients with CHB and no notable alanine aminotransferase (ALT) elevation. Design: Multinational cohort study. Setting: A community-based cohort in Taiwan (REVEAL-HBV [Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus]; REACH-B [Risk Estimation for HCC in CHB] model cohort) and 8 hospital-based cohorts from Korea and Hong Kong (GAG-HCC [Guide with Age, Gender, HBV DNA-HCC] and CU-HCC [Chinese University-HCC] cohorts). Participants: Model development: 6949 patients with CHB from a Korean hospital-based cohort. External validation: 7429 patients with CHB combined from the Taiwanese cohort and 7 cohorts from Korea and Hong Kong. Measurements: Incidence of HCC. Results: Over median follow-up periods of 10.0 and 12.2 years, the derivation and validation cohorts identified 435 and 467 incident HCC cases, respectively. Baseline HBV DNA level was one of the strongest predictors of HCC development, demonstrating a nonlinear parabolic association in both cohorts, with moderate viral loads (around 6 log10 IU/mL) showing the highest HCC risk. Additional predictors included in the new model (Revised REACH-B) were age, sex, platelet count, ALT levels, and positive hepatitis B e antigen result. The model exhibited satisfactory discrimination and calibration, with c-statistics of 0.844 and 0.813 in the derivation and validation cohorts with multiple imputation, respectively. The model yielded a greater positive net benefit compared with other strategies in the 0% to 18% threshold. Limitation: Validation in cohorts of other races and receiving antiviral treatment was lacking. Conclusion: Our new prognostic model, based on the nonlinear association between HBV viral loads and HCC risk, provides a valuable tool for predicting and stratifying HCC risk in noncirrhotic patients with CHB who are not currently indicated for antiviral treatment. Primary Funding Source: Korean government.