female

Background: Evidence supporting the use of statins for primary prevention of cardiovascular disease (CVD) in individuals aged ≥ 80 years remains limited. This study aimed to evaluate the long-term clinical benefits and safety of statins for primary prevention in patients aged 80 years and older.

Methods: We conducted a population-based retrospective cohort study using electronic medical records and pharmacy dispensing data from Clalit Health Services in Israel, covering the period from January 2015 to December 2020. Patients aged ≥ 80 years without prior CVD who were persistent statin users were compared with similar patients not receiving statins. Exclusions included prior CVD, dialysis, or death within 1 year of follow-up. Outcomes included all-cause mortality, new coronary events, myopathy, dementia, and diabetes mellitus. Cox proportional hazards models, adjusted for potential confounders, were used to assess the association between statin use and clinical outcomes.

Results: Among 15,745 patients (mean age 84.5 years; 66% female), 8413 were statin users. Over a 4-year mean follow-up, statin use was associated with a 31% reduction in mortality (HR 0.69; 95% CI: 0.34-0.74; p < 0.001) and a 20% reduction in new coronary events (HR 0.80; 95% CI: 0.68-0.94; p = 0.008). No significant differences were observed in the incidence of myopathy, diabetes, or dementia. Benefits were not observed in patients who discontinued statins before age 80.

Conclusions: In patients aged ≥ 80 years, statin therapy for primary prevention was associated with reduced all-cause mortality and coronary morbidity, without increased risk of adverse events. Early discontinuation diminished these benefits.

Importance: The incidence and risk (predictive) factors for early life food allergy development remain uncertain.

Objective: To estimate the incidence and quantify risk factors for food allergy development.

Data sources: MEDLINE and Embase were systematically searched to January 1, 2025. Data were analyzed from June 1, 2025, to November 25, 2025.

Study selection: Incidence estimates included studies confirming food allergy via food challenge. Risk factor analyses included cohort, case-control, and cross-sectional studies in any language assessing children younger than 6 years using multivariable analyses.

Data extraction and synthesis: Paired reviewers independently extracted data. Random-effects meta-analyses pooled incidence and adjusted odds ratios (ORs). Risk of bias was assessed using the QUIPS tool, and certainty of evidence assessed using GRADE.

Main outcome and measure: The primary outcome was food allergy to age 6 years.

Results: A total of 190 studies involving 2.8 million participants across 40 countries were analyzed. Among studies using food challenge, overall food allergy incidence was likely 4.7% (moderate certainty). Among 176 studies identifying 342 risk factors with varying certainty, the strongest and most certain factors included prior allergic conditions (eg, atopic dermatitis [eczema] within the first year of life [OR, 3.88; risk difference [RD], 12.0%; 95% CI, 8.8%-15.7%], allergic rhinitis [OR, 3.39; RD, 10.1%; 95% CI, 6.7%-14.4%], and wheeze [OR, 2.11; RD, 5.0%; 95% CI, 2.1%-8.8%]), severity of atopic dermatitis (OR, 1.22; RD, 1.0%; 95% CI, 0.6%-1.6%), increased skin transepidermal water loss (OR, 3.36; RD, 10.0%; 95% CI, 6.3%-14.8%), filaggrin gene sequence variations (OR, 1.93; RD, 4.2%; 95% CI, 2.4%-6.4%), delayed solid food introduction (eg, peanut after age 12 months [OR, 2.55; RD, 6.8%; 95% CI, 1.9%-14.6%]), infant antibiotic use (first month [OR, 4.11; RD, 12.8%; 95% CI, 0.4%-40%], first year [OR, 1.39; RD, 1.8%; 95% CI, 0.8%-3.1%], during pregnancy [OR, 1.32; RD, 1.5%; 95% CI, 0.6%-2.5%]), male sex (OR, 1.24; RD, 1.1%; 95% CI, 0.7%-1.6%), firstborn child (OR, 1.13; RD, 0.6%; 95% CI, 0.3%-1.0%), family history of food allergy (eg, mother [OR, 1.98; RD, 4.4%; 95% CI, 2.5%-6.8%], father [OR, 1.69; RD, 3.2%; 95% CI, 1.3%-5.5%], both parents [OR, 2.07; RD, 4.8%; 95% CI, 1.3%-5.5%], siblings [OR, 2.36; RD, 6.0%; 95% CI, 4.4%-8.0%]), parental migration (OR, 3.28; RD, 9.7%; 95% CI, 4.9%-16.3%), self-identification as Black (vs White [OR, 3.93; RD, 12.1%; 95% CI, 5.2%-22.5%], vs non-Hispanic White [OR, 2.23; RD, 5.5%; 95% CI, 3.0%-8.7%]), and cesarean delivery (OR, 1.16; RD, 1.0%; 95% CI, 0.3%-1.2%). Factors like low birth weight, postterm birth, maternal diet, and stress during pregnancy showed no significant risk difference.

Conclusions and relevance: In this meta-analysis, the most credible risk factors associated with development of childhood food allergy are a combination of major and minor risk factors, including early allergic conditions (atopic march/diathesis), delayed allergen introduction, genetics, antibiotic exposure, demographic factors, and birth-related variables.

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.