Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity.

Importance: Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. Objective: To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting. Design, Setting, and Participants: In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024. Exposures: Tirzepatide or semaglutide in formulations labeled for T2D, on or off label. Main Outcomes and Measures: On-treatment weight change in a propensity score-matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared. Results: Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). Rates of gastrointestinal AEs were similar between groups. Conclusions and Relevance: In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.

Pharmacokinetics of ampicillin during venovenous extracorporeal membrane oxygenation: A case report.

The presence of extracorporeal membrane oxygenation (ECMO) in addition to underlying critical illness can affect the pharmacokinetics and pharmacodynamics of drugs that are often required to treat this patient population. While ampicillin is the preferred agent for the treatment of susceptible Enterococcus faecalis infections, there are no in vivo pharmacokinetic studies regarding ampicillin dosing in patients receiving ECMO. This case report consists of two patients on venovenous ECMO with E. faecalis bloodstream infections in which ampicillin serum concentrations were measured. Pharmacokinetic parameters were calculated using a one compartment open model. Ampicillin trough levels were 5.87 and 39.2 mg/L for patients A and B, respectively. Based on these results, ampicillin concentrations were found to be above the minimum inhibitory concentration (MIC) for 100% of the dosing interval. The findings of this case report demonstrate that therapeutic concentrations of ampicillin can be obtained in patients on ECMO and therapeutic drug monitoring can be utilized to ensure adequate serum concentrations are achieved.

Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities.

BACKGROUND: The successful development of multiple COVID-19 vaccines has led to a global vaccination effort to reduce severe COVID-19 infection and mortality. However, the effectiveness of the COVID-19 vaccines wane over time leading to breakthrough infections where vaccinated individuals experience a COVID-19 infection. Here we estimate the risks of breakthrough infection and subsequent hospitalization in individuals with common comorbidities who had completed an initial vaccination series. METHODS: Our study population included vaccinated patients between January 1, 2021 to March 31, 2022 who are present in the Truveta patient population. Models were developed to describe 1) time from completing primary vaccination series till breakthrough infection; and 2) if a patient was hospitalized within 14 days of breakthrough infection. We adjusted for age, race, ethnicity, sex, and year-month of vaccination. RESULTS: Of 1,218,630 patients in the Truveta Platform who had completed an initial vaccination sequence between January 1, 2021 and March 31, 2022, 2.85, 3.42, 2.75, and 2.88 percent of patients with CKD, chronic lung disease, diabetes, or are in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.46 percent of the population without any of these four comorbidities. We found an increased risk of breakthrough infection and subsequent hospitalization in individuals with any of the four comorbidities when compared to individuals without these four comorbidities. CONCLUSIONS: Vaccinated individuals with any of the studied comorbidities experienced an increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the people without any of the studied comorbidities. Individuals with immunocompromising conditions and chronic lung disease were most at risk of breakthrough infection, while people with CKD were most at risk of hospitalization following breakthrough infection. Patients with multiple comorbidities have an even greater risk of breakthrough infection or hospitalization compared to patients with none of the studied comorbidities. Individuals with common comorbidities should remain vigilant against infection even if vaccinated.

Racial inequality in COVID-treatment and in-hospital length of stay in the US over time.

Introduction: Demonstrated health inequalities persist in the United States. SARS-CoV-2 (COVID) has been no exception, with access to treatment and hospitalization differing across race or ethnic groups. Here, we aim to assess differences in treatment with remdesivir and hospital length of stay across the four waves of the pandemic. Materials and methods: Using a subset of the Truveta data, we examine the odds ratio (OR) of in-hospital remdesivir treatment and risk ratio (RR) of in-hospital length of stay between Black or African American (Black) to White patients. We adjusted for confounding factors, such as age, sex, and comorbidity status. Results: There were statistically significant lower rates of remdesivir treatment and longer in-hospital length of stay comparing Black patients to White patients early in the pandemic (OR for treatment: 0.88, 95% confidence interval [CI]: 0.80, 0.96; RR for length of stay: 1.17, CI: 1.06, 1.21). Rates became close to parity between groups as the pandemic progressed. Conclusion: While inpatient remdesivir treatment rates increased and length of stay decreased over the beginning course of the pandemic, there are still inequalities in patient care.

Sex differences in behavior and expression of CGRP-related genes in a rodent model of chronic migraine.

OBJECTIVE: The objectives of this study were to develop a preclinical rodent model that produces migraine-like behaviors based on International Headache Society diagnostic criteria, to determine whether sex differences are present, and to determine whether expression of calcitonin gene-related peptide (CGRP) and the genes encoding its receptor in trigeminal ganglion or medulla correlates with those behaviors. BACKGROUND: Few animal studies of migraine have tested behaviors associated with migraine diagnostic criteria. In this study, changes in activity and in mechanical sensitivity of facial regions following application of inflammatory soup (IS) or vehicle (phosphate-buffered saline [PBS]) to the dura were measured to model changes in routine activity and allodynia. CGRP, an important mediator of migraine pathogenesis, and the 3 components of its receptor, calcitonin-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and receptor component protein (RCP) mRNAs were quantified in the trigeminal ganglion and medulla to identify baseline sex differences and changes associated with application of IS or PBS to the dura. METHODS: Male and female Sprague-Dawley rats were implanted with a dural cannula. Groups of rats were treated with 10 or 20 µL volumes of IS or PBS. Baseline behavioral testing was conducted prior to surgery and again at 7 days postsurgery, and dural application of IS or PBS was performed repeatedly for a total of 8 applications. Locomotor activity was assessed using force plate actimetry during and following application to provide information on distance traveled, bouts of low mobility, spatial confinement, and focused energy. Periorbital and perimasseter sensory testing was performed 20 minutes post-application to measure allodynia. The rats were sacrificed 30 minutes following the final dural treatment, tissue was dissected and total RNAs were isolated from ipsilateral trigeminal ganglia and ipsilateral medulla. Quantitative real-time polymerase chain reactions were used to measure the expression of amplified constructs using gene-specific primers for CGRP, RAMP1, CLR, and RCP. RESULTS: Both males and females showed behavioral effects of IS application, but there were pronounced sex differences. Females showed effects at the lower dose, and activity changes were present for a longer duration, but males required fewer applications of IS to exhibit behavioral changes. Females showed increased withdrawal responses for periorbital and perimasseter mechanical testing (10 µL IS groups), and males showed increased perimasseter withdrawal responses (20 µL IS group). In the trigeminal ganglion, there were no baseline sex differences in CGRP-encoding mRNA, but females had lower baseline expression of RAMP1, CLR, and RCP-encoding mRNAs. In the medulla, females had higher baseline levels of CGRP-encoding mRNAs and lower baseline levels of RAMP1, CLR, and RCP-encoding mRNAs than males. Both IS and PBS increased expression of mRNAs encoding CGRP, RAMP1, RCP, and CLR in the trigeminal ganglion in males, but in females, only CLR and RCP were increased. In the medulla both IS and PBS increased expression of CGRP, CLR in males and CLR and RCP in females. Thus, expression of CGRP-related genes did not mirror the behavioral differences between IS and PBS groups. Instead, CGRP-related genes were upregulated by both IS and PBS applications. CONCLUSIONS: This study demonstrates significant changes in locomotor activity and facial allodynia associated with application of IS to the dura as well as significant sex differences, demonstrating that International Headache Society diagnostic criteria can be used to design a rodent behavioral model of migraine. In addition, there were prominent baseline sex differences in expression of CGRP and its receptor in both the trigeminal ganglion and medulla, but the majority of changes in expression of CGRP and its receptor were present in both the IS and PBS treated rats. This suggests that the CGRP pathway responds to changes in intracranial pressure or meningeal stretch, while migraine-like behaviors occur after meningeal inflammation.

Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity.

INTRODUCTION: The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. METHODS: Disposable N95 masks, including medical grade (1860, 1870+) and industrial grade (8511) masks, were treated by VHP, UV, and ethanol decontamination. Mask degradation was tested using a quantitative respirator fit testing. Pooled clinical samples of SARS-CoV-2 were applied to mask samples, treated, and then either sent immediately for real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or incubated with Vero E6 cells to assess for virucidal effect. RESULTS: Both ethanol and UV decontamination showed functional degradation to different degrees while VHP treatment showed no significant change after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection in which only ethanol treatment eliminated detectable SARS-CoV-2 RNA. CONCLUSIONS: We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.