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Xanomeline and Trospium Chloride versus Placebo for the Treatment of Schizophrenia: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed
No full textPurpose: Describe xanomeline and trospium chloride efficacy and safety/tolerability for the treatment of schizophrenia using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Methods: Categorical data were extracted from the three 5-week, randomized, double blind, placebo controlled EMERGENT-1, EMERGENT-2, and EMERGENT-3 clinical trials of xanomeline/trospium in adults with schizophrenia experiencing acute psychosis. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Severity (CGI-S), and categorical response criteria. Safety and tolerability were assessed using rates of discontinuation and treatment-emergent adverse events (TEAEs). NNT, NNH, and LHH values were calculated for each individual study as well as pooled. Results: In data from the acute EMERGENT trials, NNT estimates were significant for xanomeline/trospium vs placebo for the prespecified treatment response threshold of ≥30% reduction from baseline in PANSS total score at Week 5 (NNT=5 [95% CI, 4–8]). NNT estimates for response thresholds of ≥20% and ≥40% reduction from baseline in PANSS total score and ≥1- and ≥2-point decrease from baseline in CGI-S score were \u3c10, indicating a clinically relevant therapeutic benefit of xanomeline/trospium over placebo. Estimates of NNH vs placebo for the most common TEAEs were \u3e10, with the exception of nausea and vomiting; however, rates of discontinuations due to TEAEs of nausea, dyspepsia, or vomiting were low (NNH=49 [95% CI, 28–182]). LHH indicated an overall benefit of xanomeline/trospium vs placebo for all assessed outcomes. In indirect comparisons based on published data from trials of available antipsychotics approved for schizophrenia, xanomeline/trospium exhibited comparable or more robust NNT estimates vs placebo and was the least likely agent to be associated with weight gain or somnolence/sedation. Conclusion: In the 5-week EMERGENT clinical trials, NNT, NNH, and LHH assessments demonstrated a favorable benefit-risk profile for xanomeline/trospium. Trial Registration: ClinicalTrials.gov identifiers: NCT03697252, NCT04659161, NCT04738123
The Clinical and Molecular Characteristics of Community-Associated Staphylococcus Aureus Bacteremia in Persons Who Inject Drugs at a New York City Tertiary Care Facility During the Opioid Epidemic
No full textBackground Staphylococcus aureus (SA) bacteremia is a morbid complication of injection drug use (IDU), yet little is known about the biological and clinical factors that drive morbidity due to these infections in persons who inject drugs (PWID). Methods We reviewed all cases of community-associated S. aureus bacteremia (SAB) over a 2-year period at a large tertiary care medical center in New York City. We identified 29 PWID with community-associated SAB, who were matched randomly in a 4:1 (control:case) ratio to 112 comparisons with SAB but no IDU. Whole-genome sequencing and phylogenetic analysis were performed on SAB isolates to identify genetic and molecular similarities. Results The PWID group was younger, more unstably housed, and more frequently diagnosed with endocarditis. Genotyping results showed comparable proportions of SA sequence types (STs) between PWID and comparisons, and ST8 accounted for a plurality of infections. Phylogenetic analysis showed 2 related pairs of SA isolates, only 1 of which occurred among PWID. The highest proportion of endocarditis episodes occurred in patients with SA isolates belonging to ST5, ST7, and ST97, but we were unable to identify significant associations between complications and specific SA virulence factors. Conclusions Among PWID, we did not identify specific clusters of SA, which was clonally diverse. Possible explanations include nonoverlapping IDU networks and the fact that New York is a syringe-exchange state, which may reduce the risk of shared exposures to S. aureus. PWID demonstrate higher rates of infective endocarditis than controls and should be targeted for early multidisciplinary intervention
Factors Associated With Viral Load Suppression in Pregnant and Postpartum Women Living With HIV in Rwanda: An Open-Observational Cohort Study
No full textIntroduction: Achieving and maintaining HIV viral load suppression (VLS) in pregnant and postpartum women living with HIV (WLWH) is critical for their health and to prevent mother-to-child transmission. However, data on VLS in this population are limited. This study aimed to evaluate the prevalence and factors associated with VLS among pregnant and postpartum WLWH in Rwanda within 12 months of enrolling in antenatal care. Methods: An open observational cohort study was conducted using routine clinical data from 10 Rwandan HIV clinics in Kigali City. Data from WLWH on ART who became pregnant and were referred to PMTCT services between 2012 and 2020 were analyzed. The primary outcomes were the proportion of WLWH achieving VLS (viral load (VL) \u3c1,000 or \u3c200 copies/mL) within 12 months of antenatal registration. Logistic regression models assessed associations of VLS with socio-demographic and clinical characteristics. Results: Among 1,002 WLWH, 532 (53%) had documented VL results. The mean age was 30.4 years, with 60% aged 25–34 years. Most (83.7%) were primigravida, and 67% initiated ART before pregnancy. At antenatal care enrollment, 58% had a CD4 count ≥500 cells/uL. Within 12 months, 92% had VL \u3c1,000 copies/mL and 87% had a VL \u3c200 copies/mL. Advanced HIV disease (WHO stage 3 and 4) and lower CD4 counts were associated with lower odds of VLS. Conclusion: Among those with a recorded VL results, nine out of 10 had a VLS, particularly those without advanced HIV disease. The findings underscore the need for targeted interventions for WLWH with advanced HIV entering antenatal care
Emerging Modalities for Temporary Mechanical Circulatory Support in Cardiogenic Shock
No full textCardiogenic shock (CS) is a life-threatening medical condition that requires prompt recognition and treatment. The use of standardized CS criteria, such as the Society for Cardiovascular Angiography and Interventions criteria, can categorize patients and guide therapeutic strategies. Temporary mechanical circulatory support (MCS) devices have become valuable tools in the treatment of CS, as they can provide cardiovascular support as a bridge to recovery, cardiac surgery, or advanced therapies such as cardiac transplant or durable ventricular assist devices. The use of MCS should be tailored to each individual patient, focused on a stepwise escalation of circulatory support to support both end-organ perfusion and myocardial recovery. As newer MCS devices reduce myocardial oxygen demand without increasing ischemia, the possibility of recovery is optimized. In this review, we discuss the different modalities of MCS focusing on the mechanism of support and the advantages and disadvantages of each device
Commotio Cordis a Comprehensive Review
No full textCommotio cordis is a rare, however, potentially fatal, cardiovascular phenomenon arising from direct chest wall trauma, causing sudden cardiac arrest and potentially death. It is primarily seen in young athletes who participate in contact and organized sports. Though debated, the cause of commotio cordis is believed to involve specific timing of chest impact during ventricular electrical activity leading to severe arrhythmic events. Due to sudden onset, the first step in management is immediate and effective basic life support with automated external defibrillation, followed by advanced cardiac life support. Future considerations should include secondary prevention measures such as protective padding in contact sports. It is paramount that clinicians are vigilant in recognizing potential cases of commotio cordis in the field and provide immediate care. This review consolidates the current understanding of commotio cordis, emphasizing the importance of awareness and early intervention. Future research is warranted, including retrospective and observational studies to identify high-risk patterns or trends associated with the condition
