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Introduction Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP. Methods and analysis Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician’s orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates. Ethics and dissemination The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the antibiotics (IRB# 24–0 06 503). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT07164131 .

Importance High-quality evidence guiding opioid prescribing decisions for acute pain across common diagnoses is lacking. Objective To describe pain trajectories and patterns of opioid and nonopioid treatment use among individuals who were offered opioids for the treatment of acute pain. Design, Setting, and Participants This was a prospective cohort study of patients recruited from 5 US health systems between September 2020 and March 2023 in emergency departments (EDs), primary care clinics, dental practices, or after cesarean delivery or knee replacement. Eligible patients were opioid-naive adults aged 18 years or older at all study sites, as well as adolescents aged 15 to17 years undergoing impacted molar extraction at 1 site, who were offered an opioid prescription for acute pain. Analysis was conducted April 2023 through February 2026. Exposure Offer of a prescription for an opioid analgesic. Main Outcomes and Measures Time to pain resolution (3 consecutive reports of no pain), patterns of opioid and nonopioid treatment use, and opioid-related adverse effects, ascertained from digital questionnaires. Results Among 1708 enrolled patients (median age, 38 years [IQR, 28-52 years]; 615 [36.0%] reporting race or ethnicity underrepresented in studies of acute pain management) followed up for 180 days, 915 (53.6%) were recruited in EDs, 307 (18.0%) in primary or urgent care, 263 (15.4%) in dental settings, and 223 (13.1%) in inpatient settings. Pain sources included dental (302 patients [17.7%]), trauma or injury (302 [17.7%]), obstetric (176 [10.3%]), musculoskeletal (131 [7.7%]), and low back (100 [5.9%]). Among 1502 patients reporting pain level at least once, median time to pain resolution irrespective of the treatment approach was 20 days (IQR, 8-88 days), with longer durations for surgical pain (74 days [IQR, 30 days to not reached]) and low back pain (69 days [IQR, 18 days to not reached]). The median time to opioid discontinuation among 1189 patients (69.6%) who reported any opioid use was 7 days (IQR, 2-31 days); an estimated 10.0% (95% CI, 7.7%-12.7%) of patients used opioids for at least 90 days, with higher rates in people reporting frequent pain before enrollment. Of 1482 patients (86.8%) completing at least 1 survey during the first 2 weeks of follow-up, 1153 (77.8%) reported using any opioids and 1287 (86.8%) reported using acetaminophen or ibuprofen. Among 619 (52.1%) patients with any opioid use who reported the dose of opioids taken in the first 15 days, daily doses were low (median, 10 [IQR, 5-15] morphine milligram equivalents). Most respondents reported leftover opioids (657 of 982 responding [66.9%]). Conclusions and Relevance In this cohort study of opioid-naive patients with acute pain, opioid use was generally low dose and of short duration, although some patients reported prolonged opioid use; most reported achieving pain resolution within 3 weeks, with longer times for surgical and low back pain. The findings suggest current guidelines for multimodal treatment and for short-duration opioid prescriptions if needed will serve many but not all patients, and treatment should be tailored to address individual patients’ needs.

ABSTRACT Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke ( AIS ) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians, and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE ) approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department ( ED ) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED . Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time‐sensitive treatment and equity in care delivery.

ABSTRACT Background Older adults experience age‐related physiological changes that alter the pharmacokinetics and pharmacodynamics of certain medications, which may necessitate reduced dosing. Our objective was to assess emergency department (ED) and hospital outcomes of older patients administered opioids by emergency medical services (EMS) clinicians. Methods Retrospective cohort study of adults ≥ 65 years who received an opioid between 2019 and 2024 within a health system‐affiliated EMS agency. We excluded patients with an advanced airway and those with no documented weight. Maximum single and cumulative weight‐based opioid dosages were classified as low, therapeutic, or high. Outcomes were measured in the ED/hospital and compared using Poisson regression with Huber/White standard errors, adjusted for age, sex, vitals, Glascow Coma Scale, emergency severity index, and chief concern. Results were reported as adjusted risk ratios (aRRs). Results A total of 6406 patients, including 747 (11.7%, 95% CI: 10.9–12.5) with a high opioid dose, 3663 (57.2%, 95% CI: 56.0–58.4) with a therapeutic dose, and 1996 (31.2%, 95% CI: 30.0–32.3) with a low dose, were included. Receipt of a high maximum single opioid dose versus a low/therapeutic dose (excluding patients receiving a concomitant sedative) was associated with increased risk of altered responsiveness (aRR = 1.28, 95% CI: 1.03–1.58) and delirium (aRR = 2.43, 95% CI: 1.08–5.45) in the ED/hospital setting. When 311 (4.9%) patients who received a concomitant sedative were included, patients who received a high opioid dose similarly had an increased risk of altered responsiveness (aRR = 1.28, 95% CI: 1.06–1.56) and delirium (RR = 2.65, 95% CI: 1.25–5.59), compared to a low/therapeutic dose. There was no difference in outcomes of hypoxia, death within 30 days, or ED length of stay between dose groups. Conclusion Prehospital administration of high opioid doses to older patients was associated with increased rates of altered responsiveness and delirium. These findings highlight how out‐of‐hospital care can impact a patient's ED and hospital course.

Purpose: The anatomic position of the appendix may influence both the clinical presentation and diagnostic imaging accuracy in pediatric appendicitis, but its impact remains uncertain. This study aimed to determine the prevalence of retrocecal appendicitis in children and to evaluate whether appendix positioning affects ultrasound diagnostic performance or clinical outcomes. Methods: This was a retrospective cohort study including all children 0 to 18 years of age who presented to the Mayo Clinic Rochester Emergency Department between 2018 and 2023 and were diagnosed with appendicitis during their evaluation or subsequent hospitalization. Appendix location was determined by imaging or surgical documentation. Demographics, symptoms, signs, and complication rates were collected for patients with retrocecal appendicitis (RCA) and non-retrocecal appendicitis (NRCA). Results: Four hundred seven patients were included with 12.5% having RCA. Ultrasound was obtained in 92% of patients with RCA versus 82% of NRCA (rate difference: 10%, 95% CI: 2%-19%, P =0.018). In patients who received ultrasound imaging, findings were equivocal or falsely negative in 53% of RCA patients versus 30% of NRCA patients (RD = 24%, 9%-39%; P =0.003). Computed tomography (CT) was obtained in 51% of RCA patients versus 29% of NRCA (RD = 22%, 8%-37%; P =0.003) and was equivocal or falsely negative at similar rates in RCA (12%) and NRCA (13%; P =0.88). Clinically, there were no differences in diarrhea, emesis, location of abdominal pain, or white blood cell counts between RCA and NRCA. Rates of perforation, abscess formation, hospitalization longer than 7 days, and repeat hospitalizations were also similar. Conclusions: Retrocecal appendicitis is a common anatomic variant in children that presents with similar clinical features and outcomes compared with non-retrocecal appendicitis. However, its retrocecal position reduces the diagnostic sensitivity of limited abdominal ultrasound, often necessitating additional imaging with computed tomography. Despite these diagnostic challenges, retrocecal positioning is not associated with a worsened clinical course.

ABSTRACT Background One in five emergency department (ED) visits is by older adults aged 65+ years. Clinical practice guidelines are needed to optimize patient care by translating the best available evidence into actionable recommendations to guide person‐centered management for this medically complex and growing patient population. Our objective was to understand contributors' experiences and share best practices to inform other guideline working groups. Methods We conducted a qualitative study based on thematic analysis with an interpretivist paradigm in June–July 2025, using semi‐structured interviews of Geriatric Emergency Department (GED) Guidelines 2.0 contributors to understand their experiences. Interviews were transcribed, independently reviewed by team members, and reflexively coded to identify themes. Results We interviewed 18 participants. Four main themes emerged: (1) motivations for participation, (2) varying opportunities to be involved, (3) personal benefits, and (4) challenges for improvement. Participants contrasted the strengths of shared learning and development with the burdens of organization and coordination. Conclusion Contributors to the GED Guidelines 2.0 reported a positive experience. They joined because they wanted to contribute to better care of older patients and to achieve personal and professional goals. Many cited that their roles aligned with their strengths and expertise. They also gained skills and knowledge on systematic reviews and benefited from networking. Future groups planning a similar process should consider having multiple levels of leadership, experts in systematic reviews, regular reminders, and creative incentives to improve the process and foster improved networking opportunities within their disciplines.

Abstract Delirium is a state of acute confusion characterized by deficits in attention that occurs commonly in hospitalized older adults and is associated with adverse outcomes. Delirium may have significant implications for cognitive health, however the relationship of delirium to mild cognitive impairment (MCI) and dementia is not fully understood. To evaluate the impact of delirium on cognitive health trajectories, we leveraged the Mayo Clinic Study of Aging (MCSA), a population-based cohort study of cognitive health and aging in residents of Olmsted County, Minnesota, who are between the ages of 30 and 89 and without a previous diagnosis of dementia at enrollment. Emergency Department and hospital encounters were identified for all patients enrolled in the MCSA, and clinical notes following each encounter up to 30 days were analyzed using a previously validated natural language processing (NLP) algorithm for delirium detection. The association between delirium within 30 days of hospitalization and the development of MCI or dementia was assessed using Cox proportional hazards regression, adjusted for patient age, sex, and level of education. Initial MCSA assessment indicated normal cognition for all individuals in this cohort. We found that delirium was significantly associated with development of MCI and dementia, with 42 individuals experiencing delirium within 30 days of hospitalization; hazard ratio of 10.07 (95% CI 4.14, 24.49) for developing MCI and 19.10 (95% CI 8.40, 43.47) for dementia compared to those without delirium. Our results suggest that hospitalization with an episode of delirium can significantly impact cognitive trajectories in older adults.