Estimating the Effect of Hospital Admission on Health Care Outcomes and Spending Among Persons With Dementia: A Quasi-experimental Study: Annals of Internal Medicine: Vol 0, No 0

Background: Because transitions in care settings can be confusing for persons with dementia (PWD), hospital admissions can negatively affect their physical and cognitive function. However, the effect of hospital admissions on patient outcomes and health care spending remains largely unknown. Objective: To estimate the effects of hospital admissions on health outcomes and health care spending among PWD. Design: Quasi-experimental instrumental variable method, using emergency physicians’ admission propensity as the instrument. Setting: United States. Patients: Medicare fee-for-service beneficiaries aged 66 years or older with dementia who visited an emergency department (ED) in 2017 to 2019. Measurements: Death, inpatient days (excluding the index hospital admission), and health care spending (excluding the index ED visit and hospital admission) within 30 and 90 days of ED visits. Results: Among 872 085 ED visits (62.9% women; mean age, 83.1 years) included in the analysis, 482 208 (55.3%) resulted in hospital admission. There was no evidence that hospital admission was associated with 30-day mortality rate (adjusted risk difference, −2.6 percentage points [pp] [95% CI, −5.2 to 0.1 pp]) or inpatient days (adjusted difference, 0.1 days [CI, −0.2 to 0.5 days]). Hospital admission was associated with higher 30-day health care spending (adjusted difference, $2547 [CI, $1390 to $3703]). Patterns were similar for 90-day outcomes. Limitation: Residual confounding. Conclusion: Among Medicare beneficiaries with dementia who visited an ED, there was no evidence that hospital admission was associated with mortality rates. Under conventional statistical criteria, an effect of hospital admissions between a 5.2-pp decrease and a 0.1-pp increase in 30-day mortality rates was highly compatible with the data. On the contrary, hospital admission was associated with higher health care spending. Primary Funding Source: None.

Short Versus Longer Antibiotic Duration for Community-Acquired Pneumonia: A Multicenter Target Trial Emulation: Annals of Internal Medicine: Vol 179, No 5

Background: Shorter antibiotic courses for community-acquired pneumonia (CAP) may reduce adverse effects and resistance. However, real-world data supporting very short durations remain limited. Objective: To evaluate the safety and effectiveness of 3- to 4-day versus 5-day or more antibiotic durations in hospitalized patients with CAP who achieve clinical stability by day 3 (afebrile, no new oxygen, and stable vital signs). Design: Observational emulation of a target trial. Setting: 67 Michigan hospitals between 2017 and 2024. Patients: Adults hospitalized (non–intensive care unit) with CAP who received 3 days of antibiotics, were clinically stable by antibiotic day 3, and met the strict eligibility criteria of the Pneumonia Short Treatment trial. Intervention: 0 to 1 additional days of antibiotic treatment versus 2 or more days of additional antibiotic treatment (that is, shorter [3 to 4 days] vs. longer [≥5 days] total antibiotic duration). Measurements: The main outcome was 30-day all-cause mortality. Other outcomes included 30-day hospital readmission, urgent health care visits, and Clostridioides difficile infection. Results: Among 55 517 hospitalized patients with CAP, 5620 (10.1%) ultimately met eligibility criteria for short-course therapy after comorbidity, clinical stability, and treatment duration criteria were applied. Median age of eligible patients was 68.2 years, and 54.3% were men. Median antibiotic duration was 7 days, with only 7.9% (444 of 5620) receiving 3 to 4 days. Thirty-day adjusted risk ratios for short- versus long-course antibiotic therapy were 0.89 for mortality (95% CI, 0.01 to 2.25), 1.07 for readmission (CI, 0.81 to 1.42), 0.94 for urgent visit (CI, 0.70 to 1.28), and 1.01 for C difficile infection (CI, 0.18 to 5.68). Limitation: Few short-duration patients and potential residual confounding. Conclusion: Only 10.1% of inpatients with CAP met the strict eligibility criteria for short-course therapy. The short- and longer-course antibiotic treatment groups had similar mortality rates, and there was little difference in benefits and harms. Primary Funding Source: Blue Cross Blue Shield of Michigan and Blue Care Network.

Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 179, No 1

Background: The benefit–risk profile of systemic corticosteroids in non–COVID-19 pneumonia and acute respiratory distress syndrome (ARDS) remains debated. Purpose: To assess corticosteroid effects on mortality and infection-related complications in adults with severe pneumonia or ARDS. Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform through September 2025. Study Selection: Randomized controlled trials comparing systemic corticosteroids with placebo and usual care. Primary analysis: severe pneumonia or ARDS with corticosteroids 3 mg/kg−1 of body weight per day−1 or less (prednisone-equivalent) for 15 days or less, initiated within 7 days. Data Extraction: Paired reviewers; consensus for disagreements. Data Synthesis: From 16 831 screened records, 20 studies (15 severe pneumonia, 5 ARDS) including 3459 participants met criteria. Low-dose, short-course corticosteroids probably reduce short-term mortality in severe pneumonia (15 studies, 2445 participants; risk ratio [RR], 0.73 [95% CI, 0.57 to 0.93]; I 2 = 14%; moderate certainty) and ARDS (5 studies, 1014 participants; RR, 0.77 [CI, 0.61 to 0.99]; I 2 = 23%; moderate certainty). Corticosteroids may reduce secondary shock in severe pneumonia (9 studies, 1690 participants; RR, 0.49 [CI, 0.26 to 0.92]; I 2 = 55%; low certainty). They probably result in little to no difference in hospital-acquired infections (severe pneumonia: 7 studies, 1665 participants; RR, 0.99 [CI, 0.82 to 1.20]; I 2 = 0%; moderate certainty; ARDS: 4 studies, 677 participants; RR, 0.97 [CI, 0.59 to 1.59]; I 2 = 0%; low certainty) or secondary pneumonia (severe pneumonia: 4 studies, 1011 participants; RR, 0.96 [CI, 0.66 to 1.39]; I 2 = 0%; ARDS: 4 studies, 677 participants; RR, 0.88 [CI, 0.43 to 1.79]; I 2 = 0%; both low certainty). Evidence is very uncertain for catheter-related and bloodstream infections. Long-term mortality evidence is very uncertain for severe pneumonia. Limitation: Heterogeneous pneumonia severity classification limiting subgroup precision. Conclusion: In severe pneumonia and ARDS, adjunct corticosteroids probably reduce short-term mortality. In severe pneumonia, they may reduce secondary shock. In both conditions, corticosteroids may have little or no effect on hospital-acquired infections. Primary Funding Source: None. (PROSPERO: CRD42024536301)

Pharmacologic Treatments With Lifestyle Modifications in Nonpregnant Adults With Overweight or Obesity in Outpatient Settings: A Living Clinical Guideline From the American College of Physicians (April 2026)

Description: The American College of Physicians (ACP) developed this clinical guideline for internal medicine physicians and other clinicians caring in outpatient settings for adults with overweight or obesity. Methods: This guideline is based on systematic reviews of pharmacologic treatments in adults with overweight or obesity and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Recommendation 1: ACP suggests initiating one of the following pharmacologic treatments with lifestyle modifications for weight management in nonpregnant adults with obesity (body mass index ≥30 kg/m2) in outpatient settings (conditional recommendation): First-line treatments are semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line treatment is phentermine–topiramate (low-certainty evidence); third-line treatment is liraglutide (low-certainty evidence); fourth-line treatment is naltrexone–bupropion (low-certainty evidence). When initiating a recommended medication for weight management or switching to another recommended medication because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (for example, the requirement for monthly pregnancy tests with use of phentermine–topiramate, the contraindication to phentermine–topiramate in those with cardiovascular disease, and suicidal ideation with naltrexone–bupropion). Recommendation 2: ACP suggests initiating one of the following pharmacologic treatments with lifestyle modifications for weight management in nonpregnant adults with overweight (body mass index ≥27 to 30 kg/m2) and type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease (conditional recommendation): First-line treatments are semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line treatment is liraglutide (low-certainty evidence). When initiating a recommended medication for weight management or switching to another recommended medication because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (for example, use in pregnancy).

Staging Obesity Risk Beyond Body Mass Index: Progress Made but More to Do

Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 179, No 2

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus (T2DM) and overweight or obesity, but their association with cancer is unclear. Purpose: To investigate the risk for obesity-related cancer associated with GLP-1RAs. Data Sources: PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials from inception to August 2025. Study Selection: Randomized placebo-controlled trials reporting any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma. Data Extraction: Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Odds ratios (ORs) were pooled using random-effects meta-analysis. Data Synthesis: The review included 48 trials involving 94 245 participants. GLP-1RAs probably have little or no effect on risk for thyroid cancer (OR, 1.37 [95% CI, 0.82 to 2.31]; 1 fewer to 9 more cases per 10 000 patients treated), pancreatic cancer (OR, 0.84 [CI, 0.53 to 1.35]; 9 fewer to 6 more per 10 000), breast cancer (OR, 0.95 [CI, 0.60 to 1.49]; 10 fewer to 12 more per 10 000), or kidney cancer (OR, 1.12 [CI, 0.78 to 1.60]; 5 fewer to 13 more per 10 000) (moderate certainty). GLP-1RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty). The effect on gastric cancer is very uncertain. Results were consistent in sensitivity analyses of trials with low risk of bias and studies of semaglutide or tirzepatide and across subgroups stratified by follow-up duration, population, GLP-1RA class, weight loss profile, dose, and duration of action. Limitation: The included trials were not designed to evaluate cancer outcomes and had short follow-up. Conclusion: GLP-1RAs may have little or no effect on risk for obesity-related cancers. Longer-term studies are needed to clarify potential risks or benefits. Primary Funding Source: None. (PROSPERO: CRD42024608365)

Effect of Interventions Aimed at Reducing or Modifying Saturated Fat Intake on Cholesterol, Mortality, and Major Cardiovascular Events: A Risk Stratified Systematic Review of Randomized Trials: Annals of Internal Medicine: Vol 179, No 2

Background: Debates about optimal saturated fat advice continue. Purpose: To systematically summarize randomized trial data on reducing or modifying saturated fat intake on cholesterol, mortality, and major cardiovascular events. Data Sources: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to July 2025. Study Selection: Eligible trials enrolled adults with or without cardiovascular disease and studied the effect of reducing or modifying saturated fat intake. Data Extraction: Standard Cochrane methods. Data Synthesis: There were 17 eligible trials (66 337 participants). Risk stratified evidence provides low to moderate certainty that reducing saturated fat intake may result in a reduction in all-cause mortality (risk ratio [RR], 0.96 [95% CI, 0.88 to 1.06]), cardiovascular mortality (RR, 0.93 [CI, 0.77 to 1.11]), nonfatal myocardial infarction (MI) (RR, 0.86 [CI, 0.70 to 1.06]), and fatal and nonfatal stroke (RR, 0.83 [CI, 0.58 to 1.19]). For persons at low baseline cardiovascular risk, absolute reductions were below our thresholds of importance (5 and 10 per 1000 persons followed over 5 years for fatal and nonfatal outcomes, respectively); for those at high risk, the benefits were above our thresholds, suggesting there may be important absolute reductions. The effects were more pronounced when replacing saturated fat with polyunsaturated fat for nonfatal MI (RR, 0.75 [CI, 0.58 to 0.99]; P for interaction = 0.05; moderate credibility of subgroup effect based on Instrument to assess the Credibility of Effect Modification Analyses assessments). Limitations: Data were limited on the replacement of saturated fat with monounsaturated fat or protein. Trials varied considerably in their efficacy in reducing saturated fat intake and in their replacement macronutrients and concomitant dietary interventions, and new trials are needed to clarify uncertainty. Conclusion: For persons at low cardiovascular risk, reducing or modifying saturated fat intake has little or no benefit over a period of 5 years. Among persons at high cardiovascular risk, low- to moderate-certainty evidence was found for important reductions in mortality and major cardiovascular events, particularly for MI, with respect to replacing saturated fat with polyunsaturated fat. Primary Funding Source: None. (PROSPERO: CRD42023387377)

The Prevalence and Characteristics of Difficult Patient Encounters: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 179, No 3

Background: Patients are sometimes experienced as difficult by their providers. Purpose: To estimate the prevalence of difficult patient encounters among adults being seen in nonpsychiatric settings. Secondary goals were to assess patient and provider characteristics associated with difficulty as well as patient outcomes. Data Sources: MEDLINE, Web of Science, SciELO, ProQuest, Theses, Scopus, PsycInfo, Cochrane Central Register of Controlled Trials, Global Index Medicus, and EMBASE (inception through 7 July 2025). Study Selection: In duplicate and independently. Data Extraction: Prevalence, patient characteristics (sex, mental health diagnosis, somatization, personality disorders, and chronic pain), provider characteristics (type of provider, encounter setting, burnout, years of experience, and sex), and encounter outcomes (patient unmet expectations and satisfaction) were extracted in duplicate. Data Synthesis: The prevalence of difficult encounters among clinic patients was 0.17 (95% CI, 0.15 to 0.19). Patient characteristics that increased difficulty included personality disorders (relative risk [RR], 2.2 [CI, 1.5 to 3.1]), depression (RR, 1.9 [CI, 1.7 to 2.2]), anxiety (RR, 2.1 [CI, 1.7 to 2.6]), and chronic pain (RR, 1.9 [CI, 1.5 to 2.4]). Providers with less experience (weighted mean difference, −3.5 years [CI, −5.0 to −1.9 years]) rated more encounters as difficult. Patients perceived as difficult were more likely to have unmet visit expectations (RR, 1.9 [CI, 1.4 to 2.5]) and lower satisfaction (RR, 0.76 [CI, 0.65 to 0.88]). Limitation: Limited data and heterogeneity for many secondary analyses. Conclusion: Providers perceived 17% of clinic patients as difficult. Patients perceived as difficult were more likely to have depression, anxiety, a greater number of symptoms, personality disorders, or chronic pain. Less experienced providers were more likely to judge patients as difficult. Patients from difficult encounters had more unmet visit expectations and less satisfaction. Primary Funding Source: None. (PROSPERO: CRD42024583715)

The Potential Impact of Ending the Ryan White HIV/AIDS Program on HIV Incidence: A Simulation Study in 31 U.S. Cities

Background: With antiretroviral therapy, people with HIV can live a normal lifespan and not transmit HIV. The Ryan White HIV/AIDS Program provides care for over half of people with HIV in the United States. Objective: To estimate how many HIV infections could result from cessation of Ryan White services or interruptions lasting 18 to 42 months. Design: A compartmental HIV transmission model was used to simulate epidemics and Ryan White service use. Data Sources: The researchers calibrated model transmission to surveillance data from the U.S. Centers for Disease Control and Prevention in each city and calibrated the number of Ryan White clients to program reports. Ryan White clinic directors and administrators were surveyed to estimate how many clients would lose viral suppression if services stopped. Target Population: Simulated HIV epidemics in 31 high-burden U.S. cities. Time Horizon: Through 2030. Perspective: Not applicable. Intervention: The researchers projected HIV incidence under the following 4 scenarios: continued services, cessation in July 2025, interruption until January 2027, and interruption until January 2029. Outcome Measures: Projected excess HIV infections from 2025 to 2030. Results of Base-Case Analysis: Ending Ryan White services in July 2025 could result in 75 436 additional infections (95% credible interval [CrI], 19 251 to 134 175 infections) through 2030—a 49% (95% CrI, 12% to 86%) increase. Increases ranged from 9% (Riverside, California) to 110% (Baltimore, Maryland). Interruptions of 18 and 42 months yielded 19% and 38% more infections, respectively. Results of Sensitivity Analysis: A “conservative” analysis with lower simulated loss of suppression from observational studies projected 34 051 excess infections (95% CrI, 23 902 to 45 147 infections). Limitation: The loss of suppression if Ryan White services end may be misestimated by survey responses and observational studies. Conclusion: Disrupting Ryan White services could sharply increase HIV incidence, highlighting their critical public health value. Primary Funding Source: None.

In AF with stable CAD, an OAC alone does not increase ischemic events and reduces major bleeding vs. OAC + SAPT at a mean 22 mo

Clinical Impact Ratings GIM/FP/GP: 6 out of 7 Cardiology: 6 out of 7