STOP-BABESIOSIS Investigators, Leaf DE, Monson AE
… +104 more, Dias JA, Marcos LA, Wu U, Rossi M, Ng JH, Patell R, Hundert J, El Khoury MY, Higgs J, Smith RP, Ramsaroop V, Green A, Abdul Azim A, Weisenberg S, Kirkman LA, Ingram D, Hsu CM, Dieckhaus K, Hyson P, Burger Z, Chengsupanimit T, Stalmack T, Aber R, Golden M, Koshy M, Wright K, Cortezzo G, McLeod G, Wenzel-Rideout R, Baigorri JJ, Bagchi A, Jaser A, Socorro Matos G, Sanchez-Almanzar D, Hoge ST, Shenoy T, Krishnamurthy S, Kaunfer SA, Blau JA, Woolley A, Zamor R, Maczaj B, Kenison D, Totten A, Bateman V, Mohsin S, Lee ES, Garner J, Rath P, Wu Q, Guermazi D, London A, Arvanitis P, Yune PS, Abdullah M, Kim A, Roy J, George R, Kashfi S, Hong S, Upadrista P, Hirsch JS, Bulteel A, Sharma R, Guo T, Garcia D, Shaefi S, Yeb J, Williams G, Verma E, Gouda N, Rosenthal HR, Chan A, Zainah H, Heithaus S, Saldivar MA, Wood E, DiPalazzo J, Elias S, McAuliffe M, Abbas R, Orenstein A, Tidswell MA, Galiano P, Spencer S, Srinivasan S, Xu J, Alla S, Alidoost L, Jacobson E, Menghani SV, Kannabran P, Ogunribido DB, Ssentongo P, Powell D, Meyer L, Prabhune K, Griffiths B, Gonzalez Aponte D, Dixon G, Vannier E, Roberts SC, Farmakiotis D, Krause PJ
JAMA Intern Med
· 2026 May · PMID 41910966
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IMPORTANCE: Babesiosis is a worldwide emerging tick-borne disease with an expanding geographic range in the US, Europe, and Asia. Red blood cell exchange transfusion (ET) is often used as an adjunctive treatment for seve...IMPORTANCE: Babesiosis is a worldwide emerging tick-borne disease with an expanding geographic range in the US, Europe, and Asia. Red blood cell exchange transfusion (ET) is often used as an adjunctive treatment for severe illness from babesiosis, particularly in patients with high parasitemia, acute organ injury, or severe hemolytic anemia. Data supporting its clinical effectiveness, however, are lacking. OBJECTIVE: To test whether ET improves clinical outcomes among hospitalized adult patients with severe babesiosis. DESIGN, SETTINGS, AND PARTICIPANTS: This target trial emulation used data from a multicenter cohort study of 3233 consecutive adults hospitalized with babesiosis from 2010 to 2024 at 82 sites across the northeastern US. Patients were eligible if they had parasitemia greater than 10%, or 5% to 10% with either acute organ injury or severe hemolytic anemia. Data were analyzed from April to August 2025. EXPOSURE: Treatment with ET in the first 7 days of hospitalization. MAIN OUTCOMES AND MEASURES: A composite of in-hospital death or 30-day readmission. Outcomes were compared between patients who received ET within the first 7 days of admission and those who did not. The analysis used logistic regression, with inverse probability of treatment weighting (IPTW) to adjust for potential confounders. RESULTS: The analysis included 629 patients (median [IQR] age, 71 [63-79] years; 446 male [70.9%]), among whom 209 (33.2%) received ET in the first 7 days of hospitalization. Patients treated with ET were more severely ill at baseline than those not treated with ET (median parasitemia, 14.0% vs 7.2%); however, severity of illness characteristics were well balanced after applying IPTW. In the main analysis, the primary end point occurred in 3.6% of patients who received ET and in 9.8% who did not (adjusted odds ratio, 0.22; 95% CI, 0.09-0.51). The benefit of ET was confirmed in multiple sensitivity analyses. CONCLUSIONS AND RELEVANCE: This multicenter cohort study found that among severely ill adults hospitalized with babesiosis, the adjusted risk of in-hospital death or 30-day readmission was nearly 5-fold lower in those treated with ET vs those not treated with ET. These data support ET for severely ill patients with babesiosis, although the findings may be susceptible to unmeasured confounding. Further research is needed to identify which patients are most likely to benefit.
Silva JBB, Hsieh HT, Howe CJ
… +3 more, Gravenstein S, Reich LA, Zullo AR
JAMA Intern Med
· 2026 Jun · PMID 41910957
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IMPORTANCE: Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear. OBJECTIVE:...IMPORTANCE: Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear. OBJECTIVE: To examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018-May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026. EXPOSURES: Intensive antiviral chemoprophylaxis with oseltamivir (≥70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents). MAIN OUTCOMES AND MEASURES: Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs). RESULTS: Among 404 outbreaks in 318 NHs, 35 086 resident-trial observations (29 683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17 155 observations; 17 931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of -0.06% (95% CI, -0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of -0.96% (95% CI, -1.78% to -0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death. CONCLUSIONS AND RELEVANCE: Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.
Chu SE, Cheng CY, Chang CJ
… +10 more, Ho H, Chen HA, Chan CH, Ma MH, Chang CH, Tsai KC, Chiu KM, Chen LW, Chiang WC, Sun JT
JAMA Intern Med
· 2026 May · PMID 41870444
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IMPORTANCE: Cardiopulmonary resuscitation (CPR) guidelines recommend chest compressions at the lower half of the sternum. This may lead to aortic valve compression, which is associated with poor outcomes, while compressi...IMPORTANCE: Cardiopulmonary resuscitation (CPR) guidelines recommend chest compressions at the lower half of the sternum. This may lead to aortic valve compression, which is associated with poor outcomes, while compressions over the left ventricle are seldom achieved. OBJECTIVE: To test the hypothesis that transesophageal echocardiography (TEE) guidance during CPR to avoid aortic valve compression and target the left ventricle would improve outcomes in patients with nontraumatic out-of-hospital cardiac arrest compared with conventional CPR. DESIGN, SETTING, AND PARTICIPANTS: This cluster-randomized clinical trial (the EXECT-CPR study) was conducted from June 26 to November 19, 2023, at 1 tertiary medical center in Taiwan. Participants were adults who consecutively presented to the emergency department (ED) with nontraumatic out-of-hospital cardiac arrest. Exclusion criteria were prehospital return of spontaneous circulation, extracorporeal CPR, contraindications to TEE, prior do-not-resuscitate orders, and obvious signs of death. Complete blinding was not feasible; the allocation schedule was disclosed only to the principal investigator. INTERVENTION: Post-ED arrival CPR at TEE-guided (avoid aortic-valve compression and target the left ventricle) or guideline-recommended (the lower half of the sternum) site. MAIN OUTCOMES AND MEASURES: The primary outcome was a sustained return of spontaneous circulation (≥20 minutes). Secondary outcomes were any return of spontaneous circulation, survival to intensive care unit admission, survival to hospital discharge, cerebral performance category of 2 or lower at discharge, and intra-CPR end-tidal carbon dioxide levels. RESULTS: A total of 132 patients underwent randomization (66 in each group; median [IQR] age, 68 [55-74] years; 87 [66%] male). The primary outcome was similar between groups (TEE-guided group, 29 [44%]; conventional group, 26 [39%]; cluster-adjusted odds ratio, 1.21; 95% CI, 0.64-2.29). The secondary outcomes also did not significantly differ, except for higher intra-CPR end-tidal carbon dioxide levels in the TEE-guided group during the 11th to 20th minutes after arrival. Adverse event rates related to TEE and CPR were comparable. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial among adults transported to the emergency department with ongoing CPR for nontraumatic out-of-hospital cardiac arrest, TEE-guided CPR with an adjusted compression site after arrival did not significantly improve clinical outcomes compared with conventional CPR, although it produced potential hemodynamic benefits without increasing adverse events. Given that the trial was underpowered due to optimistic effect size assumptions, these neutral findings should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05907460.
Zhu L, Magaldi LN, Wagh IA
… +10 more, Ennis ER, Reitsma MB, Kuncio DE, Addish E, Varghese SR, Furukawa NW, Honeycutt AA, Chen Y, Linas BP, Salomon JA
JAMA Intern Med
· 2026 May · PMID 41870443
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IMPORTANCE: Injection drug use is a major risk factor for both hepatitis C virus (HCV) infection and incarceration. The high volume and rapid turnover of individuals in jails make this setting a critical access point for...IMPORTANCE: Injection drug use is a major risk factor for both hepatitis C virus (HCV) infection and incarceration. The high volume and rapid turnover of individuals in jails make this setting a critical access point for hepatitis C elimination among people who inject drugs, with potential downstream benefits for reducing community transmission. OBJECTIVE: To evaluate the health benefits, costs, and cost-effectiveness of jail-based HCV interventions. DESIGN, SETTING, AND PARTICIPANTS: This cost-effectiveness analysis extended a dynamic network simulation model of HCV transmission through injection equipment sharing among people who inject drugs to incorporate population transitions between jails and communities. Data on justice-involved individuals from the Philadelphia FIGHT program and published literature on people who inject drugs in urban settings in the US were used to model an urban correctional and community setting. Analyses were conducted between April 2024 and February 2026. INTERVENTIONS: Jail-based HCV interventions comprising varying combinations of testing at entry, treatment in jail, and HCV navigation services on release. MAIN OUTCOMES AND MEASURES: Changes in person-years of HCV infection, incidence of HCV infection, HCV-related mortality, cumulative quality-adjusted life-years (QALYs), and health care costs across 60 years, and incremental cost-effectiveness ratios (ICERs). RESULTS: The mean initial age of 1552 simulated people who inject drugs was 32 years. Without jail-based interventions, there were 21 349 person-years of infection, 662 incident infections, and 240 HCV-related deaths per 1000 people who inject drugs over the 60-year time horizon. The combined strategy of testing and treatment plus navigation reduced the cumulative person-years of infection, incidence, and HCV-related deaths in the simulated population by 35% (95% UI, 30%-39%), 47% (95% UI, 41%-54%), and 40% (95% UI, 31%-49%), respectively. The ICER of this strategy was $11 000 per QALY gained compared with no jail-based intervention, well below typical standards for benchmarking cost-effectiveness, which often use thresholds ranging from $50 000 to $150 000 per QALY gained. Providing treatment in jails in addition to testing was cost-saving or yielded lower ICERs compared with providing only testing. Strategies that incorporated navigation yielded lower ICERs than strategies that did not. The results were robust to variations in key parameter values. CONCLUSIONS AND RELEVANCE: In this cost-effectiveness analysis using a network simulation model, jail-based HCV elimination interventions, particularly those providing treatment during detention, reduced prevalent and incident HCV cases and HCV-related deaths among people who inject drugs both within and beyond jails. These interventions are a cost-effective strategy for public health decision-makers to consider.
Ahmad AI, Garg S, Jacobs J
… +11 more, Ansari Z, Al-Din TJ, Almomani A, Valencia S, Vargo J, Chatterjee A, Siddiki H, Hong L, Nicolas MA, Miller A, Shah T
JAMA Intern Med
· 2026 May · PMID 41837981
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IMPORTANCE: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are known to increase the risk of retained gastric contents. High-quality data are lacking to guide periprocedure managem...IMPORTANCE: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are known to increase the risk of retained gastric contents. High-quality data are lacking to guide periprocedure management of GLP-1 and GIP agonists. OBJECTIVE: To compare the risk of clinically significant residual gastric volume (RGV) in patients who continue vs hold 1 dose of weekly or daily GLP-1 and GIP agonists prior to sedation. DESIGN, SETTING, AND PARTICIPANTS: This randomized, single-masked clinical trial conducted at 2 large tertiary referral centers in the US included patients undergoing elective upper endoscopy (EGD) who were receiving GLP-1 or GLP-1/GIP agonists between July 2024 and May 2025. Eligible participants were adults aged 18 years or older, scheduled for EGD with or without colonoscopy, under moderate sedation or monitored anesthesia care, and taking a stable dose of a GLP-1 or GLP-1/GIP agonist for at least 1 month. Exclusion criteria were prior foregut surgery, achalasia, documented gastroparesis, RGV on previous endoscopy, gastric outlet obstruction, planned general anesthesia, or recent opioid use. Data were analyzed May 2025. INTERVENTION: Participants were randomized to either continue their medication or hold 1 dose prior to the procedure. MAIN OUTCOMES AND MEASURES: Clinically significant RGV, a composite of gastric contents that (1) precludes endoscopic examination, (2) requires premature termination or endotracheal intubation, and/or (3) results in an aspiration event that necessitates extended observation or monitoring, unplanned therapeutics, or hospital admission. RESULTS: There were 60 patients (32 holding 1 dose, 28 continuing medication) in the preplanned interim analysis (median [IQR] age, 62.5 [55.5-67.5] years; 30 female [50.0%]). Clinically significant RGV occurred in 3.1% in the hold group vs 25.0% in the continue group (absolute difference, 21.9% [90% CI, 7.0%-36.7%]; P = .003). The trial was terminated early as risk exceeded the preestablished O'Brien-Fleming stopping boundary. In the EGD-only subgroup (35 patients), clinically significant RGV occurred in 46.7% in the continue vs 5.0% in the hold groups (absolute difference, 41.7% [90% CI, 17.9%-65.4%]; P = .001). In the EGD plus colonoscopy subgroup (25 patients), who were on clear liquids the day prior, no patients had clinically significant RGV. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that continuing GLP-1 or GIP agonist in the preprocedural period increased clinically significant RGV but did not increase the risk of other adverse events. Clear liquids the day prior to the procedure may mitigate the risk of clinically significant RGV regardless of GLP-1/GIP use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06533527.
Winhusen TJ, Lofwall MR, Kropp F
… +18 more, Lewis D, Smid MC, Young JL, Hodgkins C, Krans EE, Hansen Z, Wachman EM, Schiff DM, Guille C, Rudolf V, Chowdhury T, Leeman L, Lewis M, Matthews AG, Cochran G, King J, Wilder C, Rosa C
JAMA Intern Med
· 2026 May · PMID 41837971
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IMPORTANCE: Treating opioid use disorder (OUD) in pregnancy with sublingual buprenorphine is an evidence-based practice, but it has disadvantages that could be addressed with an extended-release formulation. OBJECTIVE: T...IMPORTANCE: Treating opioid use disorder (OUD) in pregnancy with sublingual buprenorphine is an evidence-based practice, but it has disadvantages that could be addressed with an extended-release formulation. OBJECTIVE: To evaluate the effectiveness and safety of extended-release buprenorphine vs sublingual buprenorphine for OUD in pregnancy through 12 months post partum. DESIGN, SETTING, AND PARTICIPANTS: This 2-group, open-label, noninferiority, randomized clinical trial was conducted between July 2, 2020, and October 30, 2024, among adults with OUD and a singleton pregnancy of 6 to 30 weeks' gestational age at 13 outpatient cross-disciplinary peripartum OUD treatment sites. INTERVENTIONS: Randomization to sublingual or extended-release buprenorphine (weekly formulation during pregnancy, monthly formulation optional post partum if not breastfeeding). MAIN OUTCOMES AND MEASURES: The primary and key secondary outcomes were illicit opioid abstinence during pregnancy and the postpartum period, respectively, defined as the proportion of weekly collected urine samples negative for illicit opioids. If noninferiority was demonstrated at a margin of 0.15, testing for superiority was planned. Key secondary infant outcomes from medical records were opioid treatment for neonatal opioid withdrawal syndrome (NOWS; yes or no) and number of opioid treatment days for NOWS. RESULTS: Among 140 randomized participants, the mean (SD) age was 31.2 (4.6) years. There were 10 Black participants (7.1%), 10 Hispanic participants (7.1%), 116 (82.9%) White participants, and 14 participants (10.0%) who belonged to additional groups. All but 2 were already prescribed sublingual buprenorphine. Study completion was 98% through pregnancy (137 participants) and 81% through 12 months post partum (114 participants). Illicit opioid abstinence was higher during pregnancy for participants receiving extended-release vs sublingual buprenorphine (82.5% vs 72.6%; mean difference, 9.84 [95% CI, 1.72 to 17.95] percentage points; P = .009). Postpartum abstinence rates declined and were similar in both groups (60.2% vs 59.5%; mean difference, 0.65 [98% CI, -12.72 to 14.02] percentage points; P = .45). Those receiving extended-release buprenorphine experienced fewer serious adverse events during pregnancy (8.7% vs 26.8%; P = .007) and post partum (6.0% vs 18.6%; P = .04). Nonserious adverse events rates did not differ between groups, but more were deemed medication-related for extended-release participants during pregnancy (26.1% vs 7.0%; P = .003). Infants exposed to extended-release vs sublingual buprenorphine did not differ in need for opioid treatment (30.2% vs 26.5%; relative risk, 1.14 [98% CI, 0.54 to 1.99]; P = .64) or mean (SE) treatment days (10.9 [2.2] vs 14.8 [3.0] days; relative risk, 0.73 [98% CI, 0.36 to 1.51]; P = .28). At birth, extended-release-exposed neonates had larger mean (SE) head circumferences than those exposed to sublingual buprenorphine (34.0 [0.2] vs 33.4 [0.2] cm; mean difference, 0.63 [95% CI, -0.00 to 1.26] cm; P = .049). CONCLUSIONS AND RELEVANCE: The findings of this randomized clinical trial support weekly extended-release buprenorphine for OUD treatment during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03918850.