Antidepressants and alcohol use disorder: A multicenter study on the mediating role of depression symptom changes.

BACKGROUND Alcohol use disorder (AUD) and depression are highly prevalent and tied to significant psychological, physiological, social and economic consequences. Their co-occurrence presents a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains equivocal. In this multicenter, longitudinal study we investigated the relationship between antidepressant medication and changes in depression symptoms and alcohol use in AUD patients. METHODS We analyzed data from 153 detoxified AUD patients who attended a 12-week residential treatment program between 2015 and 2019. Within a mediation analysis, adopting a bootstrapping approach and a quasi-Bayesian framework, we estimated the total, direct, and mediated effects of antidepressants on the percentage of days abstinent to assess the role of changes in depression symptoms as a mediating factor. RESULTS The mediation analysis revealed a dual impact pathway model with a negative direct effect of antidepressants on abstinence (p = 0.004) and a positive indirect effect, mediated through the reduction of depression symptoms (p = 0.002). CONCLUSIONS The findings of the mediation analysis show that patients treated with antidepressants and whose depression symptoms do not improve over time show more relapses, while patients treated with antidepressants who achieve a reduction in depression symptoms show fewer relapses over time. Thus, to optimize treatment outcome, depression symptoms should be vigilantly monitored when antidepressants are prescribed during AUD treatment

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid- sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.Integrative Biolog

A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Pulling the Parachute : A Qualitative Study of Burnout\u27s Influence on Emergency Medicine Resident Career Choices

OBJECTIVES: About half of all resident physicians report symptoms of burnout. Burnout negatively influences multiple aspects of their education and training. How burnout may impact residents\u27 career choices remains unclear. The authors explored the role burnout played in residents\u27 career decisions. METHODS: This was a qualitative study among a sample of 29 emergency medicine residents from four institutions. Qualitative data were generated through four semistructured focus groups. The authors employed a constructivist approach to thematic analysis. Transcripts were coded and organized into major themes. RESULTS: Five major themes connecting burnout with residents\u27 career choices emerged: 1) residents\u27 current burnout and the prevention of future burnout figured prominently in their career considerations, 2) residents aimed to mitigate sources of burnout through their career choices, 3) residents\u27 view of clinical work as a burden and a burnout contributor spurred the pursuit of other interests, 4) faculty advice and role modeling in relation to burnout shaped residents\u27 career perspectives, and 5) residents weighed long-term burnout concerns with short-term financial needs. CONCLUSION: Burnout played an important role in multiple aspects of residents\u27 career considerations. Educators, program directors, and organization leaders can focus on identified target areas to address burnout\u27s influence on residents\u27 career decisions

Going through the motions : A qualitative exploration of the impact of emergency medicine resident burnout on patient care

Objectives: Burnout occurs frequently in emergency medicine (EM) residents and has been shown to have a negative impact on patient care. The specific effects of burnout on patient care are less well understood. This study qualitatively explores how burnout may change the way EM residents provide patient care. Methods: Qualitative data were obtained from a sample of 29 EM residents in four semistructured focus groups across four institutions in the United States in early 2019. Transcripts were coded and organized into major patient care themes. Results: Residents described many ways in which feelings of burnout negatively impacted patient care. These detrimental effects most often fit into one of four main themes: reduced motivation to care for patients, poor communication with patients, difficult interactions with health care colleagues, and impaired decision making. Conclusions: According to EM residents, burnout negatively impacts several important aspects of patient care. Resident engagement with clinical care, communication with patients and colleagues, and clinical care may suffer as a result of burnout

Intern as patient: a patient experience simulation to cultivate empathy in emergency medicine residents.

Introduction: Prior work links empathy and positive physician-patient relationships to improved healthcare outcomes. The objective of this study was to analyze a patient experience simulation for emergency medicine (EM) interns as a way to teach empathy and conscientious patient care. Methods: We conducted a qualitative descriptive study on an in situ, patient experience simulation held during EM residency orientation. Half the interns were patients brought into the emergency department (ED) by ambulance and half were family members. Interns then took part in focus groups that discussed the experience. Data collected during these focus groups were coded by two investigators using a grounded theory approach and constant comparative methodology. Results: We identified 10 major themes and 28 subthemes in the resulting qualitative data. Themes were in three broad categories: the experience as a patient or family member in the ED; application to current clinical practice; and evaluation of the exercise itself. Interns experienced firsthand the physical discomfort, emotional stress and confusion patients and families endure during the ED care process. They reflected on lessons learned, including the importance of good communication skills, frequent updates on care and timing, and being responsive to the needs and concerns of patients and families. All interns felt this was a valuable orientation experience. Conclusion: Conducting a patient experience simulation may be a practical and effective way to develop empathy in EM resident physicians. Additional research evaluating the effect of participation in the simulation over a longer time period and assessing the effects on residents\u27 actual clinical care is warranted

Intern as Patient: A Patient Experience Simulation to Cultivate Empathy in Emergency Medicine Residents

Introduction: Prior work links empathy and positive physician-patient relationships to improved healthcare outcomes. The objective of this study was to analyze a patient experience simulation for emergency medicine (EM) interns as a way to teach empathy and conscientious patient care.Methods: We conducted a qualitative descriptive study on an in situ, patient experience simulation held during EM residency orientation. Half the interns were patients brought into the emergency department (ED) by ambulance and half were family members. Interns then took part in focus groups that discussed the experience. Data collected during these focus groups were coded by two investigators using a grounded theory approach and constant comparative methodology.    Results: We identified 10 major themes and 28 subthemes in the resulting qualitative data. Themes were in three broad categories: the experience as a patient or family member in the ED; application to current clinical practice; and evaluation of the exercise itself. Interns experienced firsthand the physical discomfort, emotional stress and confusion patients and families endure during the ED care process. They reflected on lessons learned, including the importance of good communication skills, frequent updates on care and timing, and being responsive to the needs and concerns of patients and families. All interns felt this was a valuable orientation experience.Conclusion: Conducting a patient experience simulation may be a practical and effective way to develop empathy in EM resident physicians. Additional research evaluating the effect of participation in the simulation over a longer time period and assessing the effects on residents’ actual clinical care is warranted

Nutritional trials using high protein strategies and long duration of support show strongest clinical effects on mortality.

Background: There is increasing evidence from randomized-controlled trials demonstrating that nutritional support improves clinical outcomes in the population of malnourished medical inpatients. We investigated associations of trial characteristics including clinical setting, duration of intervention, individualization of nutritional support and amount of energy and protein, and effects on clinical outcomes in an updated meta-analysis. Methods: We searched Cochrane Library, MEDLINE and EMBASE, from inception to December 15, 2020. Randomized-controlled trials investigating the effect of oral and enteral nutritional support interventions, when compared to usual care, on clinical outcomes of malnourished non-critically ill medical inpatients were included. Two reviewers independently extracted data and assessed risk of bias. The primary endpoint was all cause-mortality within 12-months. Results: We included 29 randomized-controlled trials with a total of 7,166 patients. Heterogeneity across RCTs was high, with overall moderate study quality and mostly moderate or unclear risk of bias. Overall, there was an almost 30%-reduction in mortality in patients receiving nutritional support compared to patients not receiving nutritional support (253/2960 [8.5%] vs. 336/2976 [11.3%]) with an odds ratio of 0.72 (95% CI 0.57 to 0.91, p ¼ 0.006). The most important predictors for the effect of nutritional trials on mortality were high protein strategies (odds ratio 0.57 vs. 0.93, 1² = 86.3%, p for heterogenity = 0.007) and long-term nutritional interventions (odds ratio 0.53 vs. 0.85, 1² = 76.2%, p for heterogenity = 0.040). Nutritional support also reduced unplanned hospital readmissions and length of hospital stay. Conclusions: There is increasing evidence from randomized trials showing that nutritional support significantly reduces mortality, unplanned hospital readmissions and length of stay in medical inpatients at nutritional risk, despite heterogeneity and varying methodological quality among trials. Trials with high-protein strategies and long-lasting nutritional support interventions were most effective