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Abstract Background Intravenous (IV) vasopressors are the mainstay of physiological support for hemodynamically unstable patients. However, the role of oral vasopressors remains unclear. The objective of our study was to evaluate the feasibility of evaluating midodrine for critically ill patients with IV vasopressor-dependent shock. Methods We conducted a single-center, concealed-allocation, parallel-group, blinded feasibility randomized controlled trial (RCT) evaluating the effect of oral midodrine versus placebo on IV vasopressor-dependent shock in the intensive care unit (ICU). The study was performed in a medical-surgical ICU at the University of Alberta Hospital from April 2021 to July 2022. We included patients aged 18 years or older admitted to the ICU with ongoing vasopressor support with decreasing vasopressor dose(s). Patients were randomly assigned 1:1 to midodrine or a placebo for the duration of their IV vasopressor therapy. The primary outcome was study feasibility and secondary outcomes included patient-centered outcomes. Feasibility was assessed through rate of recruitment, adherence to study protocol, and patient safety. Results Twenty patients were enrolled in the study and underwent randomization (n = 11 midodrine, n = 9 control). Recruitment was recorded at 1.2 participants per month, protocol adherence was 90%, and allocation remained concealed. No adverse events were reported in either group. Sepsis was the most common cause of shock in both groups. The midodrine group had a shorter length of ICU stay of 9.6 (SD 8.7) vs 10.4 (SD 14.5) days. Hospital mortality was lower for the midodrine group (n = 2, 18.2% vs n = 4, 37.5%). Vasopressor re-initiation after 24 h was more frequent in the midodrine group (n = 4, 36.4% vs n = 2, 25%). There were no readmissions to the ICU following discharge in either group. Conclusions The evaluation of midodrine for patients in the ICU is feasible and safe. This trial will inform future large-scale RCTs regarding the utility of midodrine in critically ill patients with IV vasopressor-dependent shock. Trial registration This pilot RCT was registered at clinicaltrials.gov (NCT04489589). Registered July 27, 2020. https://clinicaltrials.gov/study/NCT04489589

OBJECTIVES:. While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients. DATA SOURCES:. We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023. STUDY SELECTION:. Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization. DATA EXTRACTION:. In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS:. We included 15 RCTs (n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8–31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis. CONCLUSIONS:. In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment.

Abstract Background Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited. Methods The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions. Discussion LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients. Trial registration ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021

Introduction Intensive care unit (ICU) lengths of stay are modified by ongoing need for haemodynamic support in critically ill patients. This is most commonly provided by intravenous vasopressor therapy. Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. However, its efficacy in treating shock in the ICU, particularly for patients weaning from intravenous vasopressors, remains uncertain. The objective of this systematic review is to determine the efficacy of midodrine in vasopressor dependent shock.Methods and analysis We will search Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library for observational trials and randomised controlled trials evaluating midodrine in critically ill patients from inception to 21 April 2022. We will also review unpublished data and relevant conference abstracts. Outcomes will include ICU length of stay, duration of intravenous vasopressor support, ICU mortality, hospital mortality, hospital length of stay and rates of ICU readmission. Data will be analysed in aggregate, where appropriate. We will evaluate risk of bias using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. We will perform trial sequential analysis for the outcome of ICU length of stay.Ethics and dissemination Ethics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication and will inform future clinical trials.PROSPERO registration number CRD42021260375.

Abstract Background Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT). Methods We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of reintubation or non-invasive ventilation at 48 h). Statistical analyses included bi-variate and Moses-Littenberg models and DerSimonian-Laird pooling of areas under ROC curve (AUROC). Results A total of 731 articles were screened. Eighteen adult and 2 pediatric studies were fulfilled pre-specified eligibility. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831–0.929] and 0.828 [0.730–0.896] for successful liberation from MV, respectively, with a pooled AUROC of 0.92 [0.88–0.97]. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP, and post-SBT BNP were 0.89 [0.83–0.95], 0.77 [0.63–0.91], and 0.85 [0.80–0.90], respectively. Conclusion The relative change in BNP during a SBT has potential value as an incremental tool after successful SBT to predict successful liberation from MV in adults. There is insufficient data to support the use of BNP in children or as an alternate test to clinical indices of SBT, or the use of ΔBNP, BNP-pre, and BNP-post as an alternate or incremental test. Trial registration PROSPERO CRD42018087474 (6 February 2018)

Black gay, bisexual, and other men who have sex with men (BMSM) experience the highest rates of HIV acquisition annually out of any population in the United States, and young BMSM (YBMSM) are heavily impacted by this inequity as they enter adulthood. Despite a high annual HIV incidence, extant literature has found BMSM to engage in fewer sexual risk behaviors than White and Hispanic/Latino men who have sex with men, resulting in a gap between risk behaviors and the inequity of HIV infection. Structural factors, such as racism and homophobia, are thus being examined in order to understand this disconnect between behavior and HIV incidence. The purpose of this systematic review was to examine the discrimination experiences of YBMSM due to racism and homophobia in the United States and to evaluate the effect of these experiences on their sexual health. Four databases (MEDLINE, CINAHL Complete, APA PsycINFO, and Sociology Source Ultimate) were searched to examine the available qualitative, quantitative, and mixed method studies relevant to the research question. Out of 17 included studies, the majority were qualitative in design and were conducted in urban settings. Racism and homophobia affected YBMSM's sense of belonging, sexual identity, and sexual partnership choices. Often, masculinity would interact with these two constructs to impact how YBMSM engaged in sexual behavior, such as condomless sex, as well as their likelihood to seek sexual health care. Future research is needed to fully understand the relationships between discrimination and sexual health to develop effective structurally responsive interventions that will help decrease the inequities experienced by YBMSM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Janek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Latinx cisgender sexually minoritized men (SMM) and transgender women (TW) in the U.S. are disproportionately affected by HIV. Although pre-exposure prophylaxis (PrEP) is a highly effective strategy for HIV prevention, rates of PrEP use among Latinx SMM and TW remain suboptimal. The main purpose of this systematic review was to (1) describe engagement in the various stages of the PrEP care continuum among Latinx SMM and TW, and (2) identify multilevel determinants that function as barriers or facilitators to engagement in the PrEP continuum of care for Latinx SMM and TW. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA). Five databases (MEDLINE, CINAHL, PsycINFO, Embase, Scopus) were searched to examine the available qualitative, quantitative, and mixed method studies relevant to the research question. A total of 56 studies were included, with the majority focusing on SMM and being cross-sectional in design. Barriers included PrEP knowledge, risk perception, intersecting stigma, and structural conditions. Community resources, social support, and PrEP navigation services facilitated engagement in the PrEP continuum of care. This review highlights the complex factors that influence PrEP care engagement among Latinx SMM and TW. These findings call for comprehensive, multilevel approaches to address inequities disparities in PrEP care engagement among these groups., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Men living with HIV (MLWH) in sub-Saharan Africa experience poor health outcomes and increased AIDS-related deaths due to stigma influencing testing and treatment uptake and adherence. PRISMA 2020 was used to report a meta-synthesis of the stigma experiences of MLWH in SSA. With the help of an expert librarian, a search of six databases was formulated and performed to examine the available qualitative and mixed method studies with qualitative results relevant to the research question. Studies focused on adult men living with HIV, with five studies specifically examining the HIV experience of men who have sex with men. Study themes were synthesized to describe MLWH's perceived, internalized, anticipated, enacted, and intersectional stigma experiences. Most studies included masculinity as a key theme that affected both testing and treatment adherence upon diagnosis. Future research is needed to better understand subpopulations, such as men who have sex with men living with HIV, and what interventions may be beneficial to mitigate the disparities among MLWH in SSA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This scoping review identified contemporary stigma-reduction studies across US health-care settings. Despite the significance of this problem, only 3 intervention studies were identified in the past 5 years. These studies highlight the value of intervening during formative training experiences and the importance of including interprofessional health-care providers in interventions. The findings relate to the novel approaches (eg, virtual patient simulations) that are used in interventions. The importance of using a participatory approach to intervention design is noted. Critical gaps in human immunodeficiency virus (HIV) stigma measurement and the lack of interventions are identified, laying a foundation for future programs and research., Competing Interests: Disclosure The authors declare that they do not have any financial conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)