Adult

Aim: The "2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia" retires and replaces the "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol."

Methods: A comprehensive literature search was conducted from October 2024 to December 2024 to identify clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Structure: The focus of this clinical practice guideline is to address the evaluation, management, and monitoring of individuals with dyslipidemias, including high blood cholesterol, hypertriglyceridemia, and elevated lipoprotein(a).

Keywords: ACC/AHA clinical practice guideline; HDL; LDL; anticholesteremic agents; atherosclerosis; atherosclerotic disease; cardiovascular disease; cardiovascular diseases; cholesterol; drug interactions; dyslipidemia(s); hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolemia; hyperlipid(a)emia/s; hyperlipoproteinemia type II; hypertriglyceridemia; hypolipidemic agents; lipids; lipoprotein(a); primary prevention; risk adjustment; risk assessment; risk factors; simvastatin; statin(s); triglycerides.

Background
Vitamin B12 deficiency is common in the elderly population and can cause severe complications. The use of certain medication has in previous studies been associated with vitamin B12 deficiency in the general population. To identify elderly patients at risk for vitamin B12 deficiency due to medication use, we evaluated the association between medication use and vitamin B12 deficiency in the elderly population.

Methods
Hospitalized geriatric patients 65 years of age or over with a serum vitamin B12 measurement within one week of the admittance date were included. Patients were classified as either B12 normal (258–635 pmol/L) or B12 deficient (< 148 pmol/L). Upon hospital admission patients’ medication use was verified. The association between vitamin B12 deficiency and the use of antacid, antiepileptic, antidiabetic, lipid lowering and other medication was evaluated by univariate and multivariate analyses.

Results
Of the 7132 patients included in the study, 532 (7.5%) had vitamin B12 deficiency and 3433 (48.1%) patients had normal vitamin B12 concentrations. Metformin use was significantly and independently (adjusted OR 2.5; 95% CI 1.7–3.6) associated with a dose-dependent higher risk of vitamin B12 deficiency. The use of other medication evaluated in this study was not associated with vitamin B12 deficiency.

Conclusions
Metformin use is significantly associated with vitamin B12 deficiency in the elderly, and this risk rises with higher metformin doses. Monitoring and timely start of vitamin B12 supplementation along with the lowest possible metformin dose are essential to prevent complications.

Background: No therapies have been approved to alter bronchiectasis progression. Dipeptidyl peptidase-1 (DPP-1) inhibitors, which target neutrophil serine protease activation, are under investigation as potential disease-modifying agents.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing DPP-1 inhibitors versus placebo in patients with non-cystic fibrosis bronchiectasis. PubMed, Cochrane, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, and ICTRP were searched from inception until April 26, 2025. Primary outcomes included time to first exacerbation and proportion of patients remaining exacerbation-free. Secondary outcomes included post-bronchodilator % Forced Expiratory Volume in 1 s (FEV1), Quality of Life-Bronchiectasis (QoL-B) questionnaire scores, and rate of adverse events. Time-to-event outcome was analyzed using Kaplan-Meier (KM)-estimated individual patient data (IPD), whereas random-effects meta-analyses were performed for remaining outcomes.

Results: 2523 patients from four RCTs were included, of whom 1689 (66.9 %) received DPP-1 inhibitors. Compared with placebo, DPP-1 inhibitors prolonged the time to first exacerbation (HR 0.79; 95 % CI: 0.71 to 0.88) and increased the proportion of patients remaining exacerbation-free (RR 1.33; 95 % CI 1.12 to 1.58). A slower decline in post-bronchodilator % FEV1 was observed (MD 1.1 %; 95 % CI 0.05 to 2.15), but no difference in QoL-B scores (MD 1.35; 95 % CI -0.72 to 3.42). The safety profile of DPP-1 inhibitors was acceptable and comparable to placebo. Moderate certainty was found across endpoints.

Conclusions: DPP-1 inhibitors prolong time to first exacerbation and reduce exacerbation rates in patients with bronchiectasis, with an acceptable safety profile. These findings support their potential as a disease-modifying strategy.

Registration: PROSPERO (CRD420251042542).

Keywords: Bronchiectasis; DPP-1 inhibitor; Dipeptidyl-peptidases and tripeptidyl-peptidases; Meta-analysis; Randomized controlled trials; Systematic review.

Importance Restless legs syndrome (RLS) is a sleep-related movement disorder that affects approximately 3% of US adults to a clinically significant extent and can cause substantial sleep disturbance.

Observations Restless legs syndrome is characterized by an overwhelming urge to move the limbs, typically the legs, often accompanied by unpleasant limb sensations (eg, achiness, tingling). Symptoms, provoked by immobility, are relieved while moving and are typically present or most severe in the evening or at night. Restless legs syndrome symptoms may lead to difficulty falling asleep, staying asleep, or returning to sleep. According to population-based studies, approximately 8% of US adults experience RLS symptoms of any frequency annually and 3% experience moderately or severely distressing symptoms at least twice weekly. Patients with RLS have impaired quality of life and elevated rates of cardiovascular disease (29.6% with coronary artery disease, stroke, or heart failure), depression (30.4%), and suicidal ideation or self-harm (0.35 cases/1000 person-years). Restless legs syndrome is common among patients with multiple sclerosis (27.5%), end-stage kidney disease (24%), and iron deficiency anemia (23.9%); during pregnancy and especially in the third trimester (22%); with peripheral neuropathy (eg, diabetic, idiopathic; 21.5%); and with Parkinson disease (20%). Other risk factors include family history of RLS, northern European descent, female sex (2:1 vs male sex), and older age (RLS prevalence of 10% in adults ≥65 years). Restless legs syndrome is diagnosed based on clinical history; polysomnography is not recommended for diagnosis. Iron supplementation with ferrous sulfate (325-650 mg daily or every other day) or intravenous iron (1000 mg) should be initiated for serum ferritin level less than or equal to 100 ng/mL or transferrin saturation less than 20%. If possible, medications associated with RLS, including serotonergic antidepressants, dopamine antagonists, and centrally acting H1 antihistamines (eg, diphenhydramine), should be discontinued. Gabapentinoids (eg, gabapentin, gabapentin enacarbil, pregabalin) are first-line pharmacologic therapy. In randomized clinical trials, approximately 70% of patients treated with gabapentinoids had much or very much improved RLS symptoms vs approximately 40% with placebo (P < .001). Dopamine agonists (eg, ropinirole, pramipexole, rotigotine) are no longer recommended as first-line medications due to the risk of augmentation, an iatrogenic worsening of RLS symptoms, which has an annual incidence of 7% to 10% with these medications. Patients who do not improve with first-line treatment or have augmented RLS often benefit from low-dose opioids (eg, methadone 5-10 mg daily).

Conclusions and Relevance Restless legs syndrome affects approximately 3% of adults and can have negative effects on sleep and quality of life. Initial management includes cessation of exacerbating medications, as well as iron supplementation for patients with low-normal iron indices. If medication therapy is indicated, gabapentinoids are first-line treatment.