U.S. Food and Drug Administration Updates in Nutrition Labeling: What Clinicians Need to Know

Management of Inpatient Elevated Blood Pressures: A Systematic Review of Clinical Practice Guidelines: Annals of Internal Medicine: Vol 177, No 4

Background: Management of elevated blood pressure (BP) during hospitalization varies widely, with many hospitalized adults experiencing BPs higher than those recommended for the outpatient setting. Purpose: To systematically identify guidelines on elevated BP management in the hospital. Data Sources: MEDLINE, Guidelines International Network, and specialty society websites from 1 January 2010 to 29 January 2024. Study Selection: Clinical practice guidelines pertaining to BP management for the adult and older adult populations in ambulatory, emergency department, and inpatient settings. Data Extraction: Two authors independently screened articles, assessed quality, and extracted data. Disagreements were resolved via consensus. Recommendations on treatment targets, preferred antihypertensive classes, and follow-up were collected for ambulatory and inpatient settings. Data Synthesis: Fourteen clinical practice guidelines met inclusion criteria (11 were assessed as high-quality per the AGREE II [Appraisal of Guidelines for Research & Evaluation II] instrument), 11 provided broad BP management recommendations, and 1 each was specific to the emergency department setting, older adults, and hypertensive crises. No guidelines provided goals for inpatient BP or recommendations for managing asymptomatic moderately elevated BP in the hospital. Six guidelines defined hypertensive urgency as BP above 180/120 mm Hg, with hypertensive emergencies requiring the addition of target organ damage. Hypertensive emergency recommendations consistently included use of intravenous antihypertensives in intensive care settings. Recommendations for managing hypertensive urgencies were inconsistent, from expert consensus, and focused on the emergency department. Outpatient treatment with oral medications and follow-up in days to weeks were most often advised. In contrast, outpatient BP goals were clearly defined, varying between 130/80 and 140/90 mm Hg. Limitation: Exclusion of non–English-language guidelines and guidelines specific to subpopulations. Conclusion: Despite general consensus on outpatient BP management, guidance on inpatient management of elevated BP without symptoms is lacking, which may contribute to variable practice patterns. Primary Funding Source: National Institute on Aging. (PROSPERO: CRD42023449250)

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease: A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials: Annals of Internal Medicine: Vol 177, No 7

Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. Primary Funding Source: National Institutes of Health. (PROSPERO: CRD42022307589)

Sodium–Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 177, No 10

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 A1c 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.

Effect of Weight Loss Interventions on the Symptomatic Burden and Biomarkers of Polycystic Ovary Syndrome: A Systematic Review of Randomized Controlled Trials: Annals of Internal Medicine: Vol 177, No 12

Background: Polycystic ovary syndrome (PCOS) is common in women of reproductive age and is associated with obesity. Clinical guidelines recommend weight loss, but the impact on the clinical manifestations of PCOS is unclear. Purpose: To quantify the effect of weight loss interventions on clinical features of PCOS, compared with usual care. Data Sources: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, and trial registries were searched from inception through June 2024. Study Selection: Randomized controlled trials comparing interventions aiming to reduce weight against usual care, including lower-intensity weight loss interventions in people with PCOS. Conversations with people with PCOS informed the outcomes. Data Extraction: Pairs of independent reviewers screened studies, extracted data, and assessed risk of bias (RoB). Outcomes included glycemic control (Homeostasis Model Assessment for Insulin Resistance [HOMA-IR], fasting insulin and glucose), hormonal markers (free androgen index [FAI] and other sex hormones), menstrual frequency, hirsutism, and PCOS-related quality of life (QoL). Pooled mean differences were obtained from random-effects meta-analysis with Knapp–Hartung adjustment. Data Synthesis: Primary analyses included 29 comparisons with 1529 participants: 13, 12, and 4 comparisons were judged as high, some, or low RoB, respectively. Twelve used behavioral interventions, 9 used glucagon-like peptide-1 (GLP1) agonists, and 8 used other weight loss medications. Weight loss interventions were associated with significantly greater improvements in HOMA-IR (mean difference, −0.45 [−0.75 to −0.15]; I 2 = 24%), FAI (mean difference, −2.03 [−3.0 to −1.07]; I 2 = 48%), and menstrual frequency (mean difference, 2.64 [0.65 to 4.63]; I2  = 43%). There was no evidence that weight loss interventions were associated with clinically or statistically significant improvements in hirsutism, QoL, or other sex hormones, which may be due to the limited power of the available data. Limitation: There was high statistical heterogeneity in the interventions, comparators, and outcomes, largely unexplained by sensitivity and subgroup analyses. Conclusion: Weight loss interventions were associated with improvements in some important features of PCOS and should be considered as a routine treatment option for people with PCOS. Primary Funding Source: National Institute for Health and Care Research School for Primary Care Research. (PROSPERO: CRD42022367488)

A Framework for Considering the Value of Race and Ethnicity in Estimating Disease Risk

Background: Accounting for race and ethnicity in estimating disease risk may improve the accuracy of predictions but may also encourage a racialized view of medicine. Objective: To present a decision analytic framework for considering the potential benefits of race-aware over race-unaware risk predictions, using cardiovascular disease, breast cancer, and lung cancer as case studies. Design: Cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey), 2011 to 2018, and NLST (National Lung Screening Trial), 2002 to 2004. Patients: U.S. adults. Measurements: Starting with risk predictions from clinically recommended race-aware models, the researchers generated race-unaware predictions via statistical marginalization. They then estimated the utility gains of the race-aware over the race-unaware models, based on a simple utility function that assumes constant costs of screening and constant benefits of disease detection. Results: The race-unaware predictions were substantially miscalibrated across racial and ethnic groups compared with the race-aware predictions as the benchmark. However, the clinical net benefit at the population level of race-aware predictions over race-unaware predictions was smaller than expected. This result stems from 2 empirical patterns: First, across all 3 diseases, 95% or more of individuals would receive the same decision regardless of whether race and ethnicity are included in risk models; second, for those who receive different decisions, the net benefit of screening or treatment is relatively small because these patients have disease risks close to the decision threshold (that is, the theoretical “point of indifference”). When used to inform rationing, race-aware models may have a more substantial net benefit. Limitations: For illustrative purposes, the race-aware models were assumed to yield accurate estimates of risk given the input variables. The researchers used a simplified approach to generate race-unaware risk predictions from the race-aware models and a simple utility function to compare models. Conclusion: The analysis highlights the importance of foregrounding changes in decisions and utility when evaluating the potential benefit of using race and ethnicity to estimate disease risk. Primary Funding Source: The Greenwall Foundation.

Comparison of Hospital Mortality and Readmission Rates by Physician and Patient Sex

Background: Little is known as to whether the effects of physician sex on patients’ clinical outcomes vary by patient sex. Objective: To examine whether the association between physician sex and hospital outcomes varied between female and male patients hospitalized with medical conditions. Design: Retrospective observational study. Setting: Medicare claims data. Patients: 20% random sample of Medicare fee-for-service beneficiaries hospitalized with medical conditions during 2016 to 2019 and treated by hospitalists. Measurements: The primary outcomes were patients’ 30-day mortality and readmission rates, adjusted for patient and physician characteristics and hospital-level averages of exposures (effectively comparing physicians within the same hospital). Results: Of 458 108 female and 318 819 male patients, 142 465 (31.1%) and 97 500 (30.6%) were treated by female physicians, respectively. Both female and male patients had a lower patient mortality when treated by female physicians; however, the benefit of receiving care from female physicians was larger for female patients than for male patients (difference-in-differences, −0.16 percentage points [pp] [95% CI, −0.42 to 0.10 pp]). For female patients, the difference between female and male physicians was large and clinically meaningful (adjusted mortality rates, 8.15% vs. 8.38%; average marginal effect [AME], −0.24 pp [CI, −0.41 to −0.07 pp]). For male patients, an important difference between female and male physicians could be ruled out (10.15% vs. 10.23%; AME, −0.08 pp [CI, −0.29 to 0.14 pp]). The pattern was similar for patients’ readmission rates. Limitation: The findings may not be generalizable to younger populations. Conclusion: The findings indicate that patients have lower mortality and readmission rates when treated by female physicians, and the benefit of receiving treatments from female physicians is larger for female patients than for male patients. Primary Funding Source: Gregory Annenberg Weingarten, GRoW @ Annenberg.

How Would You Prevent Subsequent Strokes in This Patient? Grand Rounds Discussion From Beth Israel Deaconess Medical Center

Stroke is a major cause of morbidity, mortality, and disability. The American Heart Association/American Stroke Association recently published updated guidelines on secondary stroke prevention. In these rounds, 2 vascular neurologists use the case of Mr. S, a 75-year-old man with a history of 2 strokes, to discuss and debate questions in the guideline concerning intensity of atrial fibrillation monitoring in embolic stroke of undetermined source, diagnosis and management of moderate symptomatic carotid stenosis, and therapeutic strategies for recurrent embolic stroke of undetermined source in the setting of guideline-concordant therapy.

Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 177, No 5

Background: Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown. Objective: To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake. Design: Randomized, isocaloric feeding study. (ClinicalTrials.gov: NCT03527368) Setting: Clinical research unit. Participants: Adults with obesity and prediabetes or diet-controlled diabetes. Intervention: Participants were randomly assigned 1:1 to TRE (10-hour eating window, 80% of calories before 1 p.m.) or UEP (≤16-hour window, ≥50% of calories after 5 p.m.) for 12 weeks. Both groups had the same nutrient content and were isocaloric with total calories determined at baseline. Measurements: Primary outcome was change in body weight at 12 weeks. Secondary outcomes were fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), glucose area under the curve by oral glucose tolerance test, and glycated albumin. We used linear mixed models to evaluate the effect of interventions on outcomes. Results: All 41 randomly assigned participants (mean age, 59 years; 93% women; 93% Black race; mean BMI, 36 kg/m2) completed the intervention. Baseline weight was 95.6 kg (95% CI, 89.6 to 101.6 kg) in the TRE group and 103.7 kg (CI, 95.3 to 112.0 kg) in the UEP group. At 12 weeks, weight decreased by 2.3 kg (CI, 1.0 to 3.5 kg) in the TRE group and by 2.6 kg (CI, 1.5 to 3.7 kg) in the UEP group (average difference TRE vs. UEP, 0.3 kg [CI, −1.2 to 1.9 kg]). Change in glycemic measures did not differ between groups. Limitation: Small, single-site study; baseline differences in weight by group. Conclusion: In the setting of isocaloric eating, TRE did not decrease weight or improve glucose homeostasis relative to a UEP, suggesting that any effects of TRE on weight in prior studies may be due to reductions in caloric intake. Primary Funding Source: American Heart Association.

Efficacy of a Therapeutic Pelvic Yoga Program Versus a Physical Conditioning Program on Urinary Incontinence in Women: A Randomized Trial: Annals of Internal Medicine: Vol 177, No 10

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.