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The potential impact of lipopolysaccharides (LPS) interactions on light-activated ion channels and pumps
No full textOptogenetics, the expression of light-activated ion channels and pumps, has the potential in therapeutic treatments for various pathologies. Thus, it is of interest to investigate pharmacological agents, immunological responses, and disease states like bacterial septicemia to learn if light-activated ion channels and pumps are compromised. Bacterial septicemia may impede the function of light-activated channels due to direct actions of lipopolysaccharides. This study explored the effects of activating light-sensitive channels (channelrhodopsin and halorhodopsin) before, during, and after exposure of lipopolysaccharides. Lipopolysaccharide itself did not directly impede the action of LPS but varied because of the effect on ion gradients by changes in membrane potential by lipopolysaccharides
Best Management Practices on Temporary Mechanical Circulatory Support: Joint Consensus Report of the PeriOperative Quality Initiative and the Enhanced Recovery After Surgery Cardiac Society
No full textBackground: Effective utilization of temporary mechanical circulatory support (tMCS) mandates a multifaceted understanding of patient physiology, device technology, procedural techniques, patient-device interactions, and interdisciplinary collaboration. This manuscript endeavours to provide clinicians with a practical roadmap incorporating evidence-based best practices in several key areas that delineate the initial priorities in mechanical ventilation, anticoagulation, sedation, and monitoring for patients requiring tMCS.
Methods: With an interdisciplinary, international group of clinicians and through a structured literature review, a modified Delphi method was used to achieve consensus on best practices in tMCS.
Results: Nine key questions were developed with accompanying statements to direct areas that institutions and providers should prioritize to optimize care. These questions included: what expertise is required within the interdisciplinary team to optimize patient care? How should medical centers facilitate escalation of care when indicated? What is the optimal ventilation management strategy? What are the recommended gas exchange targets to preserve end-organ function? What is the recommended timing to start or resume anticoagulation? What anticoagulation agent and monitoring approach should be used routinely? What is the optimal strategy for patient comfort and device interactions? Can a patient on tMCS be mobilized? What routine monitoring needs to be performed?
Conclusions: This review provides a comprehensive review of key management strategies leveraging the interdisciplinary team and evidence-based medical knowledge to improve patient outcomes while utilizing tMCS
Association Between Erythromycin or Clindamycin Resistance and 30-Day Mortality in Patients With MSSA Bacteremia
No full textObjectives: The objective of the present study is to assess the association of erythromycin and clindamycin susceptibilities with 30-day mortality in patients with MSSA bacteremia treated with cefazolin. Methods: Retrospective cohort study of patients with least one positive blood culture growing MSSA and treated with cefazolin for at least 3 consecutive days. Groups included patients who had an MSSA strain that was both erythromycin and clindamycin susceptible (E/C-S), the comparator group included patients with erythromycin resistant and clindamycin resistant or susceptible (E/C-R) MSSA strains. The relative risk for 30-day mortality was calculated for E/C-R compared to E/C-S along with the sensitivity and specificity for E/C-R as a predictor of 30-day mortality. Results: A total of 114 patients were eligible for analysis; with 72 (63%) categorized in the E/C-S group and 42 (37%) categorized in the E/C-R group. The primary outcome of 30-day mortality was met in 7 (10%) patients in the E/C-S group vs 7 (17%) in the E/C-R group; unadjusted relative risk (95% CI) 1.71 (0.65-4.55). The sensitivity and specificity of E/C-R as a predictor of 30-day mortality was 50% (95% CI = 23-77) and 65% (95% CI = 55-74), respectively. Conclusions: This exploratory study did not find clindamycin or erythromycin susceptibility to be associated with 30-day mortality in patients treated with cefazolin for MSSA bacteremia. The relevance of this surrogate marker in clinical practice is negligible due to its limitations, and future investigations are required to establish pragmatic means of detecting isolates which may be insufficiently treated with cefazolin.
Keywords: infectious disease
Testing a Machine Learning-Based Adaptive Motivational System for Socioeconomically Disadvantaged Smokers (Adapt2Quit): Protocol for a Randomized Controlled Trial
No full textBackground: Individuals who are socioeconomically disadvantaged have high smoking rates and face barriers to participating in smoking cessation interventions. Computer-tailored health communication, which is focused on finding the most relevant messages for an individual, has been shown to promote behavior change. We developed a machine learning approach (the Adapt2Quit recommender system), and our pilot work demonstrated the potential to increase message relevance and smoking cessation effectiveness among individuals who are socioeconomically disadvantaged.
Objective: This study protocol describes our randomized controlled trial to test whether the Adapt2Quit recommender system will increase smoking cessation among individuals from socioeconomically disadvantaged backgrounds who smoke.
Methods: Individuals from socioeconomically disadvantaged backgrounds who smoke were identified based on insurance tied to low income or from clinical settings (eg, community health centers) that provide care for low-income patients. They received text messages from the Adapt2Quit recommender system for 6 months. Participants received daily text messages for the first 30 days and every 14 days until the end of the study. Intervention participants also received biweekly texting facilitation messages, that is, text messages asking participants to respond (yes or no) if they were interested in being referred to the quitline. Interested participants were then actively referred to the quitline by study staff. Intervention participants also received biweekly text messages assessing their current smoking status. Control participants did not receive the recommender messages but received the biweekly texting facilitation and smoking status assessment messages. Our primary outcome is the 7-day point-prevalence smoking cessation at 6 months, verified by carbon monoxide testing. We will use an inverse probability weighting approach to test our primary outcome. This involves using a logistic regression model to predict nonmissingness, calculating the inverse probability of nonmissingness, and using it as a weight in a logistic regression model to compare cessation rates between the two groups.
Results: The Adapt2Quit study was funded in April 2020 and is still ongoing. We have completed the recruitment of individuals (N=757 participants). The 6-month follow-up of all participants was completed in November 2024. The sample consists of 64% (486/757) female participants, 35% (265/757) Black or African American individuals, 51.1% (387/757) White individuals, and 16% (121/757) Hispanic or Latino individuals. In total, 52.6% (398/757) of participants reported having a high school education or being a high school graduate; 70% (529/757) smoked their first cigarette within 30 minutes of waking, and half (379/757, 50%) had stopped smoking for at least one day in the past year. Moreover, 16.6% (126/757) had called the quitline before study participation.
Conclusions: We have recruited a diverse sample of individuals who are socioeconomically disadvantaged and designed a rigorous protocol to evaluate the Adapt2Quit recommender system. Future papers will present our main analysis of the trial.
Trial registration: ClinicalTrials.gov NCT04720625; https://clinicaltrials.gov/study/NCT04720625.
International registered report identifier (irrid): DERR1-10.2196/63693.
Keywords: mHealth; machine learning; smoking cessation; socioeconomically disadvantaged, biochemical verification
Benzodiazepines and Opioid co-use Among Rural People Who Use Drugs: Findings From the Rural Opioid Initiative
No full textBackground: Benzodiazepines and opioids are among the most frequently misused psychoactive substances, but their patterns of co-use (polysubstance use) in rural areas are unclear. As resources to address substance use are disproportionally scarce in rural areas, a better understanding of this polysubstance use is critical to allocate and direct interventions.
Methods: The Rural Opioid Initiative comprises 8 research cohorts spanning 10 states and 65 rural counties. Participants were recruited from January 2018 to March 2020 and eligibility included past 30-day opioid use by any route or past 30-day injection of any substance. Analyses were restricted to participants reporting past 30-day opioid use and either benzodiazepine or stimulant use. We described bivariate cross-sectional associations between benzodiazepine+opioid use, compared with stimulant+opioid use, and substance use behaviors, health outcomes, injection drug use, addiction treatment, and criminal legal system involvement.
Results: Of the 1107 ROI participants that met inclusion criteria, 10% (n = 107) reported benzodiazepine+opioid use, and 90% (n = 1000) reported stimulant+opioid use. The benzodiazepine+opioid group, compared with the stimulant+opioid group, had a higher use of opioid pain medication (73% vs 55%), gabapentin (43% vs 23%), and clonidine (12% vs 4%) to get high and used these substances more frequently; they also reported more frequent heavy episodic drinking (6.1 days per 30 days, SD = 9.4 vs 4.1 days, SD 7.5). The benzodiazepine+opioid group reported a lower prevalence in the past 6 months of law enforcement stop-and-search incidents (29% vs 48%), arrests (11% vs 28%), probation (22% vs 34%), jail/prison (18% vs 41%), and fewer days in jail/prison (4.7, SD = 19.1 days vs 15.9, SD = 35.7 days).
Conclusion: We found that benzodiazepines+opioids use was associated with more heavy episodic drinking and gabapentin use, and lower prevalence of criminal legal system involvement. These data suggest that individuals reporting benzodiazepines+opioids use have distinct behavioral patterns and outcomes that require targeted interventions for rural populations.
Keywords: alcohol drinking; benzodiazepines; criminal justice; drug overdose; gabapentin; opioid overdose; opioid-related disorders; polysubstance use; prescription drug misuse; rural population
A practical primer on clinical supervision of learners in the emergency department
No full textIntroduction: Effective supervision of learners in the clinical environment is essential for learner professional development and patient safety. Despite this importance, many supervising attendings receive little to no training around supervising learners. As faculty join emergency departments (EDs) at primary and affiliate training sites, it is essential to provide them with a framework to utilize when approaching learner supervision.
Methods: A workgroup of members from the Society for Academic Emergency Medicine (SAEM) Education Committee was formed to respond to a directive from the SAEM board to identify best practices for new clinician educators when supervising learners. Drawing on their experience and expertise in learner supervision, medical education, and faculty development, the members completed a literature search to identify best practices in supervision, with a special focus on the ED environment.
Analysis: The workgroup identified three domains that must be considered to provide effective supervision to learners: learner characteristics, supervisor characteristics, and clinical environment.
Recommendations: Implementing effective supervision in the clinical environment requires a multifaceted approach and consideration of factors for both the learner and the supervisor. Direct observation, supplemented by standardized assessment tools, is the preferred supervision method; however, the demands of our clinical environment may require supervisors to assess the learner\u27s proficiency using other methods including informal knowledge assessments, inference from oral presentations, review of clinical documentation, feedback from patients themselves, procedural walkthroughs, and secondhand information from the health care or training team
Antibiotic Treatment in Patients Hospitalized for Nonsevere COVID-19
No full textImportance: Patients hospitalized with nonsevere COVID-19 continue to receive community-acquired pneumonia (CAP) antibiotic treatment despite a low risk of bacterial coinfection. Unnecessary antibiotic prescribing contributes to global antibiotic resistance and also poses a threat to individual patients.
Objective: To examine the association of CAP antibiotic treatment started on admission with clinical outcomes among a large sample of patients hospitalized for nonsevere COVID-19 in hospitals across the US.
Design, setting, and participants: This retrospective cohort study used a target trial emulation design. Participants were adult, immunocompetent patients admitted to general care for COVID-19 from April 2020 to December 2023 at 1053 US-based acute-care hospitals that contribute data to the Premier Healthcare Database. Patients with nonpneumonia bacterial infections present on admission were excluded. Data were analyzed from April to October 2024.
Exposure: Receipt of a CAP antibiotic regimen on the day of admission.
Main outcomes and measures: The primary outcome was a composite measure of deterioration (vasopressor, high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, intermediate care, intensive care unit admission) and in-hospital mortality occurring on day 2 or later. The association between receipt of antibiotic therapy and the primary outcome was assessed using propensity methods while adjusting for a broad set of potential confounders, including cotreatments.
Results: The cohort included 520 405 patients with COVID-19 (median [IQR] age, 66 [53-78] years; 266 186 [51.2%] male), including 92 708 Black patients (17.8%), 63 619 Hispanic patients (12.2%), and 304 649 White patients (58.5%); 279 656 patients (53.7%) had Medicare insurance. A total of 160 482 patients (30.8%) were treated with a CAP antibiotic regimen on day 1 of admission. The primary composite outcome was higher in the CAP group (20.8%) compared with the unexposed (no antibiotic) group (18.4%), but the difference did not meet the predefined criteria for clinical significance (ASD, 4.1%). Patients who received CAP antibiotics had higher odds of poor clinical outcomes (propensity matched-odds ratio [OR], 1.03 [95% CI, 1.01-1.05]; P = .003; inverse probability treatment weighted-OR, 1.03 [95% CI, 1.02-1.05]; P \u3c .001; standardized mortality ratio weighted-OR, 1.10 [95% CI, 1.08-1.12]; P \u3c .001).
Conclusions and relevance: In this large cohort study of patients hospitalized with nonsevere COVID-19, there was no clinically meaningful difference in outcomes with early antibiotic treatment. Given the risks associated with unnecessary antibiotic treatment, these results argue against routine antibiotic use in this population
It\u27s Harder to Chase Pain Than It Is to Prevent It : Perinatal Individual and Care Professional Attitudes Towards Preventing Perinatal Mood and Anxiety Disorders in Obstetric Settings
No full textPurpose: Depression and anxiety disorders are prevalent in the perinatal period and disproportionately impact individuals who experience economic marginalization. \u3c 15% of at-risk individuals are referred for recommended preventative counseling interventions. Little is known about the attitudes of care professionals and perinatal individuals towards prevention. This study\u27s objective was to elicit attitudes of perinatal care professionals and individuals with lived experience of perinatal depression and anxiety who have been marginalized due to their economic status towards prevention interventions for perinatal mood and anxiety disorders in routine perinatal care settings.
Methods: We conducted semi-structured qualitative interviews with economically marginalized individuals with lived experience of perinatal anxiety or depression (n = 12) and perinatal care professionals (n = 12). We used a thematic analysis approach for data analysis.
Results: Participants endorsed generally positive attitudes towards prevention. Both individuals and professionals identified gaps in current practices and expressed interest in prevention because they felt that it could improve outcomes. Both groups described skepticism that prevention is possible. Perinatal individuals also described concerns about professional capacity, stigma, and medical mistrust while professionals had concerns about potential for harm and resource limitations. Participants emphasized the importance of professional-patient relationships and multidisciplinary teams in effective delivery of prevention care.
Conclusions: Current approaches to prevention of mood and anxiety disorders in the perinatal period are lacking. Integration of prevention into routine obstetric care is of interest to perinatal individuals and professionals as a strategy to improve outcomes and reduce care inequities. Improving education and awareness of prevention interventions may reduce skepticism towards these interventions. Steps to build communication and trust between patients and professionals are needed to improve comfort and engagement with prevention interventions.
Keywords: Anxiety; Depression; Integrated behavioral health; Perinatal; Prevention; Qualitative research
Implications and Considerations of Sexual and Gender Identities in Dynamic Psychotherapies
No full textLesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and other diverse gender and sexual identities (LGBTQIA+) youth have a disproportionately high risk of mental health issues such as depression, suicide, and substance use. Clinicians must engage in self-reflection about both obvious and subtle aspects of their identities, recognizing how these factors might influence their practice. Creating a therapeutic space, employing gender-neutral language, and being comfortable in discussing topics related to sexuality and gender diversity, can open the door for multiple opportunities to strengthen the therapeutic alliance.
Keywords: Alliance; Gender; LGBTQIA+; Psychotherapy; Sexuality; Youth
Filling the Void: The Past, Present, and Future of Left Atrial Appendage Occlusion
No full textLeft atrial appendage occlusion (LAAO) has emerged as an alternative strategy to oral anticoagulation (OAC) to mitigate the risk of thromboembolic events in patients with atrial fibrillation (AF). Endovascular LAAO devices were first developed in the early 2000s for patients with relative and absolute contraindications to OAC. Four randomized controlled trials have demonstrated the safety and efficacy of LAAO procedures, and two LAAO devices have been approved and are commercially available in the United States. Procedural complications, especially pericardial effusion, as well as subsequent peri-device leak and device-related thrombosis have decreased over time due to improved device design and implantation techniques. Many aspects of the LAAO technology continue to evolve. Intracardiac echocardiography (ICE) is used increasingly and offers distinct advantages and disadvantages compared to transesophageal echocardiography (TEE) for procedural guidance. The role of universal post-procedure surveillance imaging remains unclear. Post-LAAO antithrombotic therapy has shifted from short-term anticoagulation to immediate dual antiplatelet therapy, with ongoing research exploring the feasibility of single antiplatelet therapy. Novel devices with improved design and technology are currently undergoing clinical trials. Additionally, the patient population eligible for LAAO may significantly increase in the coming years, as ongoing trials are evaluating the effectiveness of LAAO devices in a broader population of patients with AF. In conclusion, the history, current state, and active research related to LAAO are summarized in this review article.
Keywords: Left atrial appendage occlusion; anticoagulation; atrial fibrillation; stroke