Annals of Internal Medicine最新文献

Description: In March 2020, the White House Coronavirus Task Force determined that clinicians in the United States needed expert treatment guidelines to optimally manage patients with COVID-19, a potentially life-threatening disease caused by a new pathogen for which no specific treatments were known to be effective.

Methods: The U.S. Department of Health and Human Services requested that the National Institutes of Health (NIH) take the lead in expeditiously convening a panel of experts to create "living" guidelines that would be widely accessible and capable of frequent updating as important new information became available.

Recommendations: The purpose of this article is to expand on the experiences of the NIH COVID-19 Treatment Guidelines Panel (the Panel) over the past 4 years, summarize the Panel's final recommendations for COVID-19, highlight some challenges and unanswered questions about COVID-19 management, and inform future responses to public health emergencies. The Panel was formed in March 2020, and the first iteration of the guidelines was released in April 2020. Now that the public health emergency has ended, the NIH COVID-19 Treatment Guidelines have sunsetted. This role will now fall to professional societies and organizations, such as the American College of Physicians, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the World Health Organization, all of which have been active in this area.

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain.

Objective: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA).

Design: Target trial emulation study.

Setting: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022.

Patients: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide.

Measurements: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders.

Results: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16).

Limitation: Residual confounding is possible; there was no adjustment for hemoglobin A_1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly.

Conclusion: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required.

Primary funding source: Ministry of Food and Drug Safety of South Korea.

Background: Pelvic floor yoga has been recommended as a complementary treatment strategy for urinary incontinence (UI) in women, but evidence of its efficacy is lacking.

Objective: To evaluate the effects of a therapeutic pelvic floor yoga program versus a nonspecific physical conditioning program on UI in women.

Design: Randomized trial. (ClinicalTrials.gov: NCT03672461).

Setting: Three study sites in California, United States.

Participants: Ambulatory women aged 45 years or older reporting daily urgency-, stress-, or mixed-type UI.

Intervention: Twelve-week program of twice-weekly group instruction and once-weekly self-directed practice of pelvic floor-specific Hatha yoga techniques (pelvic yoga) versus equivalent-time instruction and practice of general skeletal muscle stretching and strengthening exercises (physical conditioning).

Measurements: Total and type-specific UI frequency assessed by 3-day voiding diaries.

Results: Among the 240 randomly assigned women (age range, 45 to 90 years), mean baseline UI frequency was 3.4 episodes per day (SD, 2.2), including 1.9 urgency-type episodes per day (SD, 1.9) and 1.4 stress-type episodes per day (SD, 1.7). Over a 12-week time period, total UI frequency (primary outcome) decreased by an average of 2.3 episodes per day with pelvic yoga and 1.9 episodes per day with physical conditioning (between-group difference of -0.3 episodes per day [95% CI, -0.7 to 0.0]). Urgency-type UI frequency decreased by 1.2 episodes per day in the pelvic yoga group and 1.0 episode per day in the physical conditioning group (between-group difference of -0.3 episodes per day [CI, -0.5 to 0.0]). Reductions in stress-type UI frequency did not differ between groups (-0.1 episodes per day [CI, -0.3 to 0.3]).

Limitation: No comparison to no treatment or other clinical UI treatments; conversion to videoconference-based intervention instruction during the COVID-19 pandemic.

Conclusion: A 12-week pelvic yoga program was not superior to a general muscle stretching and strengthening program in reducing clinically important UI in midlife and older women with daily UI.

Primary funding source: National Institutes of Health.

Background: Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited.

Objective: To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard.

Design: Cross-sectional study. (ClinicalTrials.gov: NCT03264898).

Setting: Three U.S. academic medical centers and affiliated endoscopy units.

Participants: Patients aged 50 to 85 years undergoing screening or surveillance colonoscopy.

Intervention: Participants completed 5 different FITs before their colonoscopy, including 4 qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, QuickVue iFOB) and 1 quantitative test (OC-Auto FIT, which was run at the manufacturer's threshold for positivity of >100 ng/mL).

Measurements: The primary outcome was test performance (sensitivity and specificity) for each of the 5 FITs for advanced colorectal neoplasia (ACN), defined as advanced polyps or CRC. Positivity rates, positive and negative predictive values, and rates of unevaluable tests were compared. Multivariable models were used to identify factors affecting sensitivity.

Results: A total of 3761 participants were enrolled, with a mean age of 62.1 years (SD, 7.8); 63.2% of participants were female, 5.7% were Black, 86.4% were White, and 28.7% were Hispanic. There were 320 participants with ACN (8.5%), including 9 with CRC (0.2%). The test positivity rate varied 4-fold (3.9% to 16.4%) across FITs. Rates of unevaluable FITs ranged from 0.2% to 2.5%. The sensitivity for ACN varied from 10.1% to 36.7%, and specificity varied from 85.5% to 96.6%. Differences in sensitivity between FITs were all statistically significantly different except between Hemosure iFOB and QuickVue iFOB, and specificity differences were all statistically significantly different from one another. In addition to FIT brand, distal location of ACN was also associated with higher FIT sensitivity.

Limitation: The study did not assess the programmatic sensitivity of annual FIT.

Conclusion: Although considered a single class, FITs have varying test performance for detecting ACN and should not be considered interchangeable.

Primary funding source: National Institutes of Health.

Background: False-positive results on screening mammography may affect women's willingness to return for future screening.

Objective: To evaluate the association between screening mammography results and the probability of subsequent screening.

Design: Cohort study.

Setting: 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC).

Patients: 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis.

Measurements: Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities.

Results: Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, -1.9 percentage points [CI, -3.1 to -0.7 percentage points]), short-interval follow-up (-15.9 percentage points [CI, -19.7 to -12.0 percentage points]), or biopsy (-10.0 percentage points [CI, -14.2 to -5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (-20 to -25 percentage points) or biopsy (-13 to -14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result.

Limitation: Women could receive care at non-BCSC facilities.

Conclusion: Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk.

Primary funding source: National Cancer Institute.

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 A_1c (HbA_1c; 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 HbA_1c, 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 HbA_1c 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.