Buprenorphine for acute pain in older adults: a systematic review with meta-analysis.

BACKGROUND: Buprenorphine, a partial opioid agonist, has emerging evidence as an alternative to full agonist opioids for treatment of acute pain. This systematic review aimed to evaluate the safety and efficacy of buprenorphine for acute pain in older adults. METHODS: PubMed Medline, Embase, Cochrane Central Register of Controlled Trials, CINHAL, Web of Science database, and Google Scholar were searched. We included articles that reported buprenorphine as an intervention to treat acute pain among patients 60 years or older. Primary outcome was difference in pain scores for patients treated with buprenorphine compared to other analgesia. Secondary outcomes included adverse events, opioid consumption, and patient satisfaction. Meta-analysis was conducted on difference in pain scores and differences in nausea and vomiting. RESULTS: Twenty-two studies were included (n = 2610). Buprenorphine was administered as nerve blocks in six studies, transdermal in eight, intravenous or intramuscular in five, sublingual in two studies, and both intravenous and sublingual in one study. 10 out of 20 (50%) studies found improved pain control in buprenorphine groups. Meta-analysis found no significant difference in pain scores between buprenorphine and control analgesia at 24 hours (Cohen's d = -0.29 [95% CI -0.85 to 0.27]) and 7 days (Cohen's d = -0.89 [95% CI -2.66-0.88]). Six studies (54.5%) found reduced opioid consumption in patients receiving buprenorphine. There was no difference in adverse effects in most studies. CONCLUSIONS: This review did not find buprenorphine to be superior to alternative analgesia; however the mixed results provide scientific rationale for future studies testing buprenorphine in older populations.

Is the Compassion of Anesthesiologists Associated With Postoperative Pain and Patient Experience? A Prospective Cohort Study.

BACKGROUND: Patient perception of physician compassion may be associated with improved health outcomes, yet it is unclear whether it is associated with postoperative pain reduction or improved patient experience metrics in same-day surgery patients. We hypothesized that higher anesthesiologist compassion during the preanesthesia interview, rated by patients, is associated with lower postoperative pain via the anxiety pathway in same-day surgery patients. We also performed exploratory correlation analysis to assess whether compassion was associated with less opioid consumption and improved patient experience in same-day surgery patients. METHODS: We conducted a single-center, prospective, observational cohort study in American Society of Anesthesiologists (ASA) physical status I to III patients scheduled to undergo same-day surgery with anesthesia. Compassion was scored using a validated 5-item tool. State anxiety (SA) and trait anxiety (TA) were measured using the State-Trait Anxiety Inventory. Pain scores were obtained using a 0 to 10 Likert scale. Daily opioid use was recorded. Patient experience was assessed using the Consumer Assessment of Healthcare Providers and Systems Outpatient and Ambulatory Surgery Survey (OAS CAHPS) and the Surgical Care CAHPS. Mediation analysis was used to assess the association between compassion and pain scores via the anxiety pathway. Spearman correlation was performed to test for association between the compassion score and the secondary outcomes. RESULTS: A total of 147 subjects completed the study with a median age of 50 years and 81% female. Fifty percent underwent breast surgery, 35% abdominal surgery, and the rest underwent gynecological and urological surgeries. The median (Q1-Q3) postoperative pain scores on postoperative days 0 and 3 days later were 4 (1.5-6) and 3 (1-5), respectively.Mediation analysis results showed a same-day anxiety-mediated effect (95% confidence interval [CI]) of compassion on pain of -0.08 (-0.13 to -0.02), attributing to 9% of the total effect. On postoperative day 0, an increase in compassion was associated with a significant average drop in pain of between 0.02 and 0.13. In addition, higher compassion was correlated with better patient experience metrics (ρ= -0.53 [95% CI, -0.64 to -0.39]). CONCLUSIONS: The study results suggest that an anxiety-mediated pathway exists through which compassionate care may help improve the patient's perception of postoperative pain on the day of surgery (before discharge from the hospital). Higher compassion was also associated with better patient experience metrics.

Emergency department staff compassion is associated with lower fear of enacted stigma among patients with opioid use disorder.

OBJECTIVES: Fear of enacted stigma (fear of discrimination or being treated unfairly) is associated with decreased health care-seeking behaviors among patients with opioid use disorder (OUD). We sought to describe the prevalence of fear of enacted stigma among patients presenting to the emergency department (ED) with OUD and to test whether experiencing greater compassion from ED staff is associated with lower fear of enacted stigma. METHODS: We conducted a cross-sectional study in the ED of an academic medical center between February and August 2023. We included adult patients with OUD presenting to the ED and assessed patient experience of compassion from ED staff using a previously validated 5-item compassion measure (score range 5-20). The primary outcome measure was fear of enacted stigma in the ED, measured using the validated 9-item subscale of the Substance Abuse Self-Stigma Scale (score range 9-45). RESULTS: Of the 116 subjects enrolled, 97% (95% confidence interval [CI] 91%-99%) reported some degree of stigma, with a median (interquartile range) score of 23 (16-31). In a multivariable model adjusting for potential confounders, patient experience of greater ED compassion was independently associated with lower fear of enacted stigma, ß = -0.66 (95% CI -1.03 to -0.29), suggesting that every 1-point increase in the 5-item compassion measure score is associated with a 0.66-point decrease in the fear of enacted stigma score. CONCLUSIONS: Among ED patients with OUD, fear of enacted stigma is common. Patient experience of compassion from ED staff is associated with lower fear of enacted stigma. Future research is warranted to test if interventions aimed at increasing compassion from ED staff reduce patient fear of enacted stigma among patients with OUD.

Cardiac Extracorporeal Membrane Oxygenation in Community Cardiac Surgery Program: Are the Results Comparable?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) outcomes in small centers are commonly considered less favorable than in large-volume centers. New ECMO protocols and procedures were established in our regional community hospital system as part of a cardiogenic shock initiative. This retrospective study aims to evaluate the outcomes of veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (ECPR) in a community hospital system with cardiac surgery capability and assess whether protocol optimization and cannulation standards result in comparable outcomes to larger centers whether the outcomes of this new ECMO program at the community hospital setting were comparable to the United States averages. METHODS: Our regional system comprises five hospitals with 1500 beds covering southwestern New Jersey, with only one of these hospitals having cardiac surgery and ECMO capability. In May 2021, the new ECMO program was initiated. Patients were screened by a multidisciplinary call, cannulated by our ECMO team, and subsequently treated by the designated team. We reviewed our cardiac ECMO outcomes over two years, from May 2021 to April 2023, in patients who required ECMO due to cardiogenic shock or as a part of extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: A total of 60 patients underwent cardiac ECMO, and all were VA ECMO, including 18 (30%) patients who required ECPR for cardiac arrest. The overall survival rate for our cardiac ECMO program turned out to be 48% (29/60), with 50% (22/42) in VA ECMO excluding ECPR and 39% (7/18) in the ECPR group. The hospital survival rate for the VA ECMO and ECPR groups was 36% (15/42) and 28% (5/18), respectively. The ELSO-reported national average for hospital survival is 48% for VA ECMO and 30% for ECPR. Considering these benchmarks, the hospital survival rate of our program did not significantly lag behind the national average. CONCLUSIONS: With protocol, cannulation standards, and ECMO management optimized, the VA ECMO results of a community hospital system with cardiac surgery capability were not inferior to those of larger centers.

Probabilistic association of differentially expressed genes with cis-regulatory elements.

Differential gene expression in response to perturbations is mediated at least in part by changes in binding of transcription factors (TFs) and other proteins at specific genomic regions. Association of these cis-regulatory elements (CREs) with their target genes is a challenging task that is essential to address many biological and mechanistic questions. Many current approaches rely on chromatin conformation capture techniques or single-cell correlational methods to establish CRE-to-gene associations. These methods can be effective but have limitations, including resolution, gaps in detectable association distances, and cost. As an alternative, we have developed DegCre, a nonparametric method that evaluates correlations between measurements of perturbation-induced differential gene expression and differential regulatory signal at CREs to score possible CRE-to-gene associations. It has several unique features, including the ability to use any type of CRE activity measurement, yield probabilistic scores for CRE-to-gene pairs, and assess CRE-to-gene pairings across a wide range of sequence distances. We apply DegCre to six data sets, each using different perturbations and containing a variety of regulatory signal measurements, including chromatin openness, histone modifications, and TF occupancy. To test their efficacy, we compare DegCre associations to Hi-C loop calls and CRISPR-validated CRE-to-gene associations, establishing good performance by DegCre that is comparable or superior to competing methods. DegCre is a novel approach to the association of CREs to genes from a perturbation-differential perspective, with strengths that are complementary to existing approaches and allow for new insights into gene regulation.

Partial pressure of carbon dioxide/pH interaction and its association with mortality among patients mechanically ventilated in the emergency department.

OBJECTIVES: There is currently conflicting data as to the effects of hypercapnia on clinical outcomes among mechanically ventilated patients in the emergency department (ED). These conflicting results may be explained by the degree of acidosis. We sought to test the hypothesis that hypercapnia is associated with increased in-hospital mortality and decreased ventilator-free days at lower pH, but associated with decreased in-hospital mortality and increased ventilator-free days at higher pH, among patients requiring mechanical ventilation in the emergency department (ED). METHODS: Secondary analysis of patient level data from prior clinical trials and cohort studies that enrolled adult patients who required mechanical ventilation in the ED. Patients who had a documented blood gas while on mechanical ventilation in the ED were included in these analyses. The primary outcome was in-hospital mortality, and secondary outcome was ventilator-free days. Mixed-effects logistic, linear, and survival-time regression models were used to test if pH modified the association between partial pressure of carbon dioxide (pCO2) and outcome measures. RESULTS: Of the 2348 subjects included, the median [interquartile range (IQR)] pCO2 was 43 (35-54) and pH was 7.31 (7.22-7.39). Overall, in-hospital mortality was 27%. We found pH modified the association between pCO2 and outcomes, with higher pCO2 associated with increased probability of in-hospital mortality when pH is below 7.00, and decreased probability of in-hospital mortality when pH is above 7.10. These results remained consistent across multiple sensitivity and subgroup analyses. A similar relationship was found with ventilator-free days. CONCLUSIONS: Higher pCO2 is associated with decreased mortality and greater ventilator-free days when pH is >7.10; however, it is associated with increased mortality and fewer ventilator-free days when the pH is below 7.00. Targeting pCO2 based on pH in the ED may be a potential intervention target for future clinical trials to improve clinical outcomes.

A qualitative assessment of emergency physicians' experiences with robust emergency department buprenorphine bridge programs.

OBJECTIVES: Emergency departments (EDs) are a critical point of entry into treatment for patients struggling with opioid use disorder (OUD). When initiated in the ED, buprenorphine is associated with increased addiction treatment engagement at 30 days when initiated. Despite this association, it has had slow adoption. The barriers to ED buprenorphine utilization are well documented; however, the benefits of prescribing buprenorphine for emergency physicians (EPs) have not been explored. This study utilized semistructured interviews to explore and understand how EPs perceive their experiences working in EDs that have successfully implemented ED bridge programs (EDBPs) for patients with OUD. METHODS: Semistructured interviews were conducted with EPs from four geographically diverse academic hospitals with established EDBPs. Interviews were recorded and transcribed, and emergent themes were identified using codebook thematic analysis. Analysis credibility and transparency were confirmed with peer debriefing. RESULTS: Twenty-two interviews were conducted across the four sites. Three key themes were constructed during the analyses: (1) provided EPs agency; (2) transformed EPs' emotions, attitudes, and behaviors related to treating patients with OUD; and (3) improved EPs' professional quality of life. CONCLUSIONS: Participants in this study reported several common themes related to participation in their hospital's BP. Overall our results suggest that physicians who participate in EDBPs may feel a renewed sense of fulfillment and purpose in their personal and professional lives. These positive changes may lead to increased job satisfaction in hospitals that have successfully launched EDBP.

Pilot implementation of a telemedicine care bundle: Antimicrobial stewardship, patient satisfaction, clinician satisfaction, and usability in patients with sinusitis.

BACKGROUND: Telemedicine-specific clinical pathways (CPWs), coupled with electronic health record (EHR) order panels, provide an opportunity to ensure evidence and guideline concordant care for conditions at risk for inconsistent diagnoses and management strategies. Standardized provider and patient-facing illness scripts may fill gaps in clinicians' communication skills secondary to a training deficit in virtual care delivery. We aimed to implement and assess the impact of a novel care bundle for sinusitis on antimicrobial use, patient satisfaction, clinician satisfaction, and usability in patients with sinusitis. METHODS: A sinusitis care bundle (SCB) for virtual urgent care patients included a sinusitis CPW with communication scripts, sinusitis order panels (SOP), and a patient education smart-phrase (SPESP) within visit instructions. Antimicrobial use was assessed during a 15-month period prior to the start of SCB element implementations and 14-months following, using statistical process control charts. Patient satisfaction was measured using Likert-style surveys. Clinician satisfaction was assessed using a novel survey addressing the SCB-targeted domains (decision support, communication, efficiency, usability, and overall satisfaction). RESULTS: There were 69,785 and 64,019 evaluable patients in the pre-care and post-care bundle periods, respectively. Despite a significant increase in patients receiving a sinusitis diagnosis in the post-care bundle period (3.2% pre- vs. 6.2% post-, p < 0.001), antimicrobial prescribing decreased by 3.9% (p < 0.001), with statistical process control evidence of special cause change. There was a 5.1% decrease (p < 0.001) in negative patient survey responses after implementation. Clinician survey revealed substantial agreement in the domains relating to improving communication with patients and/or families, with the highest satisfaction for the SPESP over the SOP. CONCLUSIONS: Implementation of a telemedicine care bundle for patients diagnosed with sinusitis can balance multiple elements of quality care. The combination of a clinical care pathway, standardized language, and order panels within the EHR has the potential to improve patient satisfaction and decrease antimicrobial prescribing.

Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements.

Tauopathies are a group of neurodegenerative diseases defined by abnormal aggregates of tau, a microtubule-associated protein encoded by MAPT. MAPT expression is near absent in neural progenitor cells (NPCs) and increases during differentiation. This temporally dynamic expression pattern suggests that MAPT expression could be controlled by transcription factors and cis-regulatory elements specific to differentiated cell types. Given the relevance of MAPT expression to neurodegeneration pathogenesis, identification of such elements is relevant to understanding disease risk and pathogenesis. Here, we performed chromatin conformation assays (HiC & Capture-C), single-nucleus multiomics (RNA-seq+ATAC-seq), bulk ATAC-seq, and ChIP-seq for H3K27ac and CTCF in NPCs and differentiated neurons to nominate candidate cis-regulatory elements (cCREs). We assayed these cCREs using luciferase assays and CRISPR interference (CRISPRi) experiments to measure their effects on MAPT expression. Finally, we integrated cCRE annotations into an analysis of genetic variation in neurodegeneration-affected individuals and control subjects. We identified both proximal and distal regulatory elements for MAPT and confirmed the regulatory function for several regions, including three regions centromeric to MAPT beyond the H1/H2 haplotype inversion breakpoint. We also found that rare and predicted damaging genetic variation in nominated CREs was nominally depleted in dementia-affected individuals relative to control subjects, consistent with the hypothesis that variants that disrupt MAPT enhancer activity, and thereby reduced MAPT expression, may be protective against neurodegenerative disease. Overall, this study provides compelling evidence for pursuing detailed knowledge of CREs for genes of interest to permit better understanding of disease risk.