Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle.

Smooth muscle cell (SMC) contraction and vascular tone are modulated by phosphorylation and multiple modifications of the thick filament, and thin filament regulation of SMC contraction has been reported to involve extracellular regulated kinase (ERK). Previous studies in ferrets suggest that the actin-binding protein, calponin 1 (CNN1), acts as a scaffold linking protein kinase C (PKC), Raf, MEK and ERK, promoting PKC-dependent ERK activation. To gain further insight into this function of CNN1 in ERK activation and the regulation of SMC contractility in mice, we generated a novel Calponin 1 knockout mouse (Cnn1 KO) by a single base substitution in an intronic CArG box that preferentially abolishes expression of CNN1 in vascular SMCs. Using this new Cnn1 KO mouse, we show that ablation of CNN1 has two effects, depending on the cytosolic free calcium level: (1) in the presence of elevated intracellular calcium caused by agonist stimulation, Cnn1 KO mice display a reduced amplitude of stress and stiffness but an increase in agonist-induced ERK activation; and (2) during intracellular calcium depletion, in the presence of an agonist, Cnn1 KO mice exhibit increased duration of SM tone maintenance. Together, these results suggest that CNN1 plays an important and complex modulatory role in SMC contractile tone amplitude and maintenance.

Pathogen disgust is associated with interpersonal bias among healthcare professionals.

Background and objectives: Pathogen avoidance is a fundamental motive that shapes many aspects of human behavior including bias against groups stereotypically linked to disease (e.g. immigrants, outgroup members). This link has only been examined in convenience samples and it is unknown how pathogen avoidance processes operate in populations experiencing prolonged and heightened pathogen threat such as healthcare professionals. We examined whether healthcare professionals demonstrate the same link between pathogen disgust and intergroup bias as has been documented among the general population. Methodology: Participants (N = 317; 210 healthcare professionals) were recruited using snowball sampling to take an online survey. Participants completed the Three Domain Disgust Scale to assess pathogen, sexual and moral disgust. Participants then rated their perceptions of a fictitious immigrant group ('Krasneeans') and the degree to which they endorsed group-binding moral values. Results: Compared to control participants, healthcare professionals reported lower levels of pathogen disgust, but not sexual or moral disgust. However, regardless of profession, higher pathogen disgust was associated with viewing Krasneeans as less likeable and more unclean. Additionally, regardless of profession, higher pathogen disgust was associated with greater endorsement of group-binding moral values, although healthcare professionals reported greater overall endorsement of group-binding moral values than did control participants. Conclusions and implications: Although healthcare professionals demonstrated lower levels of pathogen disgust, they nevertheless exhibited largely the same relationship between pathogen disgust and interpersonal biases as did control participants. One practical implication of this association is that pathogen avoidance motives may contribute to inequitable patient treatment in healthcare settings.

Trends in the surgical management of kidney cancer by tumor stage, treatment modality, facility type, and location.

Partial nephrectomy (PN) is an alternative to radical nephrectomy (RN) in the appropriate localized renal tumor. The scope of PN has expanded over time and, since the advent and proliferation of minimally invasive surgery, more surgeons have access to and have been trained in laparoscopic and robotic technology. Amid the changing surgical landscape, we sought to characterize the trends in management by cancer stage, institution type, and geographic location using the National Cancer Database (NCDB). We queried the NCDB for patients with kidney cancer from 2004 to 2019. Overall, 241,311 patients who underwent PN or RN were included in the study. The nephrectomy approach was categorized as robotic partial (RPN), robotic radical (RRN), laparoscopic partial (LPN), laparoscopic radical (LRN), open or unspecified partial (OPN), and open or unspecified radical (ORN). The categorical variables were presented as frequency and percentages. Overall, there was an increase in the utilization of robotic approaches from 2010 to 2019. For cT1 tumors, the use of RPN and RRN increased from 14.27 to 33.06% and 5.24% to 19.63%, respectively. The use of ORN for cT2 and cT3 tumors declined, with rates dropping from 54.71 to 10.76% and 64.71 to 46.64%, respectively. Conversely, the utilization of RRN rose during this period. However, ORN remained the most common approach for cT3 tumors. The use of RPN increased across different facility types, with the highest utilization observed in academic/research programs. The use of ORN for cT2 and cT3 tumors declined across facility types, although it remained most prevalent in community cancer programs. The use of robot-assisted surgery to treat localized renal cancer increased in the US between 2010 and 2019 across all stages of disease. RPN became the most used approach for cT1 disease, while LRN was preferred for cT2 disease. ORN remained the approach of choice for cT3 disease throughout the study period. Trends in facility type and geographic location largely mirrored the overall trends.

Contemporary Practices for Medical Evaluation of the Psychiatric Patient in the Emergency Department.

Although emergency department (ED) visits for patients with mental illness are frequent, medical evaluation (i.e., "medical screening") of patients presenting with psychiatric complaints is inconsistent. This may largely be related to differing goals for medical screening, which often vary according to specialty. Although emergency physicians typically focus on stabilization of life-threatening diseases, psychiatrists tend to believe that care in the ED is more comprehensive, which often places the two fields at odds. The authors discuss the concept of medical screening, review the literature on this topic, and offer a clinically oriented update to the 2017 American Association for Emergency Psychiatry consensus guidelines on medical evaluation of the adult psychiatric patient in the ED.

Effectiveness of a Self-Administered Computerized Mental Health Screening Tool in the Emergency Department.

OBJECTIVE: The authors sought to determine the effectiveness of a self-administered computerized mental health screening tool in a general acute care emergency department (ED). METHODS: Changes in patient care (diagnosis of a past-year psychiatric disorder, request for psychiatric consultation, psychiatric referral at discharge, or transfer to psychiatric facility) and patient ED return visits (3 months after discharge vs. 3 months before) were assessed among ED physicians (N=451) who received patients' computerized screening reports (N=207) and those who did not (N=244). All patients received copies of screening results. RESULTS: The computerized mental health screening tool identified previously undiagnosed psychiatric problems. However, no statistically significant differences were found in physician care or patient ED return visits. CONCLUSIONS: Computerized mental health screening did not result in further psychiatric diagnoses or treatment; it also did not significantly reduce patient ED return visits. Collaboration among EDs and mental health treatment agencies, organizations, and researchers is needed to facilitate appropriate treatment referrals and linkage.

Emergency Departments Treating Veterans for Suicide: Ensuring Quality Care for Veterans Outside of Department of Veterans Affairs Health Care Facilities.

INTRODUCTION: Veterans die by suicide at higher rates than nonveterans. Given that the emergency department is often the first point of entry to healthcare following a suicide attempt, it would be beneficial for community providers to have knowledge of the characteristics, medical issues, and effective treatments most often associated with those having served in the military to ensure guideline concordant and quality suicide care. This study aimed to identify assessment and referral practices of emergency departments at rural community hospitals related to care for suicidal veterans and explore the feasibility and acceptability of identifying veterans in need of postdischarge aftercare. METHODS: This qualitative exploratory study involved content analysis of semistructured interviews. Ten emergency clinicians from 5 rural Arkansas counties with high suicide rates were interviewed about their experiences working with suicidal patients within the emergency department and perceptions of assessment, management, and referral practices. RESULTS: Although most of the emergency departments had a process for assessing for suicide risk, emergency clinicians did not always feel confident in their knowledge of assessing and caring for suicidal patients. Military history was not included in assessment, treatment, or aftercare planning, nor were brief interventions such as safety planning or lethal means safety education provided. DISCUSSION: Best practices for suicide assessment and management of veterans exist; however, challenges specific to the emergency department regarding staff training and engaging the community to effectively link at-risk veterans to needed care hinder implementation. Veteran-inclusive assessment and intervention practices could enhance the quality of care provided in community emergency departments.

A Quality Measurement Framework for Emergency Department Care of Psychiatric Emergencies.

As a primary access point for crisis psychiatric care, the emergency department (ED) is uniquely positioned to improve the quality of care and outcomes for patients with psychiatric emergencies. Quality measurement is the first key step in understanding the gaps and variations in emergency psychiatric care to guide quality improvement initiatives. Our objective was to develop a quality measurement framework informed by a comprehensive review and gap analysis of quality measures for ED psychiatric care. We conducted a systematic literature review and convened an expert panel in emergency medicine, psychiatry, and quality improvement to consider if and how existing quality measures evaluate the delivery of emergency psychiatric care in the ED setting. The expert panel reviewed 48 measures, of which 5 were standardized, and 3 had active National Quality Forum endorsement. Drawing from the measure appraisal, we developed a quality measurement framework with specific structural, process, and outcome measures across the ED care continuum. This framework can help shape an emergency medicine roadmap for future clinical quality improvement initiatives, research, and advocacy work designed to improve outcomes for patients presenting with psychiatric emergencies.

Emergency Department Management of Suicidal Ideation: Challenges, Misperceptions, and Hope.

Behavioral crises continue to escalate across the United States. Our country has one of the highest suicide rates amongst developed nations. More than 45,000 U.S. citizens are dying annually now from suicide. Many with suicidal ideation seek care in Emergency Departments in hospital systems under resourced to handle this growing public health crisis. Evidenced-based screening, risk stratification, and treatment continues to evolve and is not standardized. Improved suicide education needs to be more broadly applied across healthcare and society. Missouri as a state is making concentrated efforts to improve resources and care for those with suicidal ideation. Many challenges need to be overcome and time will tell if new statewide initiatives will reduce Missouri's high rate of suicide.

A Propensity-Matched Comparison of the Perioperative Outcomes Between Single-Port and Multi-Port Robotic Assisted Partial Nephrectomy: A Report from the Single Port Advanced Research Consortium (SPARC).

Purpose: Single-port (SP) robotic surgery is a new technology and early in its adoption curve. The goal of this study is to compare the perioperative outcomes of SP to multi-port (MP) robotic technology for partial nephrectomy. Materials and Methods: This is a prospective cohort study of patients who have undergone robot-assisted partial nephrectomy using SP and MP technology. Baseline demographic, clinical, and tumor-specific characteristics and perioperative outcomes were compared using χ2, t-test, and Mann-Whitney U test in the overall cohort and in a 1:1 propensity score-matched cohort, adjusting for baseline characteristics. Results: After propensity matching, 146 SP patients were matched with 146 MP patients. SP and MP groups had similar mean age (58 ± 12 years vs 59 ± 12 years; p = 0.606) and proportion of men (54.11% vs 52.05%; p = 0.725). The SP had a longer mean ischemia (18.29 ± 10.49 minutes vs 13.79 ± 6.29 minutes; p < 0.001). Estimated blood loss (EBL) and length of hospital stay (LOS), operative time, positive margin rate, and any complication rate were similar between the two groups. Conclusions: SP partial nephrectomy had a longer ischemia time, and a comparable LOS, EBL, operative time, positive margin rates, and complication rates to MP. These early data are encouraging. However, the role of SP requires further study and should evaluate safety and long-term data when compared with the standard MP technique.

Remote surgical education using synthetic models combined with an augmented reality headset.

Objective: The objective was to investigate the use of an augmented reality headset to remotely train clinicians on medical devices using anatomic models. Design: Disease-specific phantoms were developed to train physicians in mpMRI-guided fusion prostate biopsy, brachytherapy, and rectal spacer insertion. Training was remotely demonstrated using 1-way virtual video conferencing format. Participants responded to an educational content survey. A heads-up display with software and augmented reality was used for remote 2-way training with the proctor and student using on their own phantoms. Setting: The virtual video meeting took place during a prostate cancer conference in 2020, while the augmented reality training occurred in 2021. The proctor and student wore a heads-up display containing a projector and webcam where the ultrasound image was displayed onto a see-through optic along with the physician's hands. The heads-up display allowed the proctor to teach by line-of-sight while the student watched and repeated the steps. Participants: Faculty with expertise with the medical devices used in these procedures provided training to urologists unfamiliar with these techniques. Results: Participants responded that the 1-way training on the phantoms was realistic and mimicked human tissue. A total of 70.9% requested more training or training on the phantoms. The remote training platform was successfully beta tested at the 2 locations in transperineal prostate biopsy and rectal spacer insertion. Conclusion: Remote training using augmented reality eliminates the need for travel. For training programs and workshops, this technology may mitigate the risk of infectious exposures, reduce training cost, and increase proctor availability, allowing training from their own institution or clinic.This investigation qualifies for the Accreditation Council for Graduate Medical Education competency in medical knowledge.

Feasibility of Peer-Delivered Suicide Safety Planning in the Emergency Department: Results From a Pilot Trial.

Objective: The emergency department (ED) is an important site for suicide prevention efforts, and safety planning has been identified as a best practice for suicide prevention among ED patients at increased suicide risk. However, few ED clinicians are prepared to assess suicide risk or guide patients in the creation of safety plans. This study was a pilot randomized controlled trial of the feasibility, acceptability, and preliminary effects of safety planning by individuals with lived experience of suicide attempt or of severe suicidal ideation but without medical training (i.e., peers) in the ED. Methods: Patients at risk for suicide in a general ED were randomly assigned to receive peer-delivered or mental health provider­delivered safety planning. Intervention feasibility measures included ED length of stay, safety plan completeness, and safety plan quality. Acceptability measures included patient satisfaction. Preliminary effects were assessed as number of ED returns within the 3 months after the ED visit. Results: Data from 31 participants were available for analysis. Compared with participants with provider-delivered safety planning, participants with peer-delivered safety planning had similar ED lengths of stay, higher safety plan completeness, and higher safety plan quality. Acceptability of the safety planning process was similar for the two groups. Compared with participants receiving provider-delivered safety planning, participants receiving peer-delivered planning had significantly fewer ED visits during the subsequent 3 months than during the 3 months preceding the ED visit. Conclusions: Peer-delivered safety planning is feasible and acceptable and may result in fewer return ED visits. These findings provide preliminary support for peer-delivered safety planning in the ED.

Haloperidol Versus Ziprasidone With Concomitant Medications and Other Predictors of Physical Restraint Duration in the Emergency Department.

BACKGROUND: Patients with severe agitation are frequently encountered in the emergency department (ED). At times, these patients are physically restrained and given calming medications; however, little is known about the effects of medications and other predictors on restraint duration. OBJECTIVE: Our aim was to compare restraint duration when haloperidol or ziprasidone was used as the primary antipsychotic with or without concomitant medications, and to identify predictors of restraint duration. METHODS: We performed a review of a retrospective cohort of physically restrained ED patients between January 1, 2013 and November 30, 2017. An unadjusted analysis and adjusted linear regression model were used to evaluate the effect of antipsychotic choice on restraint duration, controlling for sex, age, race, homelessness, arrival in restraints, re-restraint during visit, concomitant medications (i.e., benzodiazepines or anticholinergics), additional medications given during restraint, time of day, and patient disposition. RESULTS: In 386 patients (319 haloperidol, 67 ziprasidone), the average restraint duration was 2.4 h (95% confidence interval [CI] 2.2 to 2.6 h). There were no differences in physical restraint times between ziprasidone and haloperidol groups in the unadjusted (mean difference 0.12 h; 95% CI -0.42 to 0.66 h) or adjusted analyses (-12.7%; 95% CI -33.9% to 8.6%). Haloperidol given with diphenhydramine alone was associated with decreased restraint duration (-30.8%; 95% CI -50.6% to -11.1%) The largest association with restraint duration was administration of additional sedating medications during restraint, prolonging restraint by 62% (95% CI 27.1% to 96.9%). In addition, compared with White patients, Black patients spent significantly more time restrained (mean difference 33.9%; 95% CI 9.0% to 58.9%). CONCLUSIONS: Restraint duration of agitated ED patients was similar when haloperidol or ziprasidone was used as the primary antipsychotic. However, race and additional medications given during restraint were significantly associated with restraint duration.

The Impact of Coronavirus Disease 2019 on US Emergency Departments.

Behavioral emergencies in the United States have been increasing, with some studies reporting a doubling in the number of people experiencing symptoms related to mental health conditions, although overall visits to US emergency departments (EDs) decreased during the coronavirus disease 2019 (COVID-19) pandemic. The uncertainty surrounding the COVID-19 pandemic caused many people to avoid health care facilities, including EDs, even if they may have otherwise sought emergency care, and was associated with increases in new behavioral health diagnoses. Measures to limit the spread of COVID-19 led to people limiting their in-person contact with others, likely exacerbating preexisting mental health issues.

Utility of a controlled amphetamine withdrawal paradigm among adults who use methamphetamine: A pilot clinical trial.

BACKGROUND: The continued increase in prevalence of methamphetamine use in the United States has resulted in a significant increase in the number of patients entering treatment for methamphetamine use. However, no robustly efficacious pharmacologic treatment for methamphetamine use or withdrawal has been identified to date after stopping methamphetamine use. AIMS: Given the association between methamphetamine withdrawal and relapse during early treatment, this study tested a controlled d-amphetamine withdrawal paradigm among methamphetamine-using individuals. METHODS: Treatment-seeking adults who used methamphetamine (N = 34; 47% female; 100% white) were enrolled in a 4-week, randomized, double-blind, placebo-controlled trial in a residential setting, in which all participants were maintained on d-amphetamine (30 mg BID) during week 1, then half were switched to placebo during weeks 2-3. All participants received placebo during week 4. Outcomes included vital signs, withdrawal, cravings for methamphetamine, mood, and cognition. Bivariate analyses tested treatment group differences on baseline demographic and outcome variables. Repeated measures models examined main and interaction effects of treatment over time. RESULTS/OUTCOMES: Participants were successfully randomized and safely stabilized on d-amphetamine. Craving for methamphetamine increased during weeks 2-3 in the placebo group relative to those on d-amphetamine. Interactions with age and heart rate were noted. CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first double-blind, placebo-controlled trial measuring pharmacologic effects of abruptly stopping controlled d-amphetamine administration in adults who use methamphetamine. Results support the potential of this withdrawal paradigm to further examine the efficacy of pharmacologic agents in ameliorating methamphetamine withdrawal symptoms.

Association of the COVID-19 pandemic and dying at home due to ischemic heart disease.

The coronavirus disease 2019 (COVID-19) pandemic has been associated with a declining volume of patients seen in the emergency department. Despite the need for seeking urgent care for conditions such as myocardial infarction, many people may not seek treatment. This study seeks to measure associations between the COVID-19 pandemic and location of death among individuals who died from ischemic heart disease (IHD). Data obtained from death certificates from the Arkansas Department of Health was used to conduct a difference-in-difference analysis to assess whether decedents of IHD were more likely to die at home during the pandemic (March 2020 through September 2020). The analysis compared location of death for decedents of IHD pre and during the pandemic to location of death for decedents from non-natural causes. Before the pandemic, 50.0% of decedents of IHD died at home compared to 57.9% dying at home during (through September 2020) the pandemic study period (p < .001). There was no difference in the proportion of decedents who died at home from non-natural causes before and during the pandemic study period (55.8% vs. 53.5%; p = .21). After controlling for confounders, there was a 48% increase in the odds of dying at home from IHD during the pandemic study period (p < .001) relative to the change in dying at home due to non-natural causes. During the study period, there was an increase in the proportion of decedents who died at home due to IHD. Despite the ongoing pandemic, practitioners should emphasize the need to seek urgent care during an emergency.

Adherence to guideline creation recommendations for suicide prevention in the emergency department: A systematic review.

OBJECTIVES: Suicide rates in the United States rose 35.2% from 1999-2018. As emergency department (ED) providers often have limited training in management of suicidal patients and minimal access to mental health experts, clinical practice guidelines (CPGs) may improve care for these patients. However, clinical practice guidelines that do not adhere to quality standards for development may be harmful both to patients, if they promote practices based on flawed evidence, and to ED providers, if used in malpractice claims. In 2011, the Institute of Medicine created standards to determine the trustworthiness of CPGs. This review assessed the adherence of suicide prevention CPGs, intended for the ED, to these standards. Secondary objectives were to assess the association of adherence both with first author/organization specialty (ED vs non-ED) and with inclusion of recommendations on substance use, a potent risk factor for suicide. METHODS: This is a systematic review of available suicide-prevention CPGs for the ED in both peer-reviewed and gray literature. This review followed the PRISMA standards for reporting systematic reviews. RESULTS: Of 22 included CPGs, the 7 ED-sponsored CPGs had higher adherence to quality standards (3.1 vs 2.4) and included the highest-rated CPG (ICAR2E) identified by this review. Regardless of specialty, nearly all CPGs included some mention of identifying or managing substance use. CONCLUSIONS: Most suicide prevention CPGs intended for the ED are written by non-ED first authors or organizations and have low adherence to quality standards. Future CPGs should be developed with more scientific rigor, include a multidisciplinary writing group, and be created by authors working in the practice environment to which the CPG applies.

Consensus Recommendations on the Treatment of Opioid Use Disorder in the Emergency Department.

The treatment of opioid use disorder with buprenorphine and methadone reduces morbidity and mortality in patients with opioid use disorder. The initiation of buprenorphine in the emergency department (ED) has been associated with increased rates of outpatient treatment linkage and decreased drug use when compared to patients randomized to receive standard ED referral. As such, the ED has been increasingly recognized as a venue for the identification and initiation of treatment for opioid use disorder, but no formal American College of Emergency Physicians (ACEP) recommendations on the topic have previously been published. The ACEP convened a group of emergency physicians with expertise in clinical research, addiction, toxicology, and administration to review literature and develop consensus recommendations on the treatment of opioid use disorder in the ED. Based on literature review, clinical experience, and expert consensus, the group recommends that emergency physicians offer to initiate opioid use disorder treatment with buprenorphine in appropriate patients and provide direct linkage to ongoing treatment for patients with untreated opioid use disorder. These consensus recommendations include strategies for opioid use disorder treatment initiation and ED program implementation. They were approved by the ACEP board of directors in January 2021.

Intramuscular medication for treatment of agitation in the emergency department: A systematic review of controlled trials.

BACKGROUND: Severely agitated patients in the emergency department (ED) are often sedated with intramuscularly-administered medications. The evidence base underlying particular medication choices is surprisingly sparse, as existing reviews either have methodological limitations or have included data collected outside of emergent settings. OBJECTIVES: The objective of this review was to examine all controlled trials in emergent settings that have used standardized scales to measure the effectiveness of intramuscular medication for the treatment of acute agitation. METHODS: This review was registered in Prospero as CRD42018105745. PubMed, International Pharmaceutical Abstracts, Web of Science, PsycINFO, and clinicaltrials.gov were searched for prospective controlled trials investigating intramuscular antipsychotics for agitation. Articles were assessed for bias across five domains using the revised Cochrane Risk of Bias Tool. RESULTS: Eight studies were eligible for inclusion in the systematic review, none of which had a low risk of bias. Five studies had a moderate risk of bias with heterogenous designs, populations, and treatments. These studies seemed to suggest that second generation antipsychotics (SGAs) likely reduce agitation as effectively as first generation antipsychotics (FGAs) plus an adjunctive medication with similar or lower risk of side effects. CONCLUSIONS: Existing trials on the use of intramuscular antipsychotics in the ED/psychiatric ED setting were small, heterogenous, and at a moderate or high risk of bias. Given the clinical importance of this topic, further prospective investigations are desperately needed but are currently unfeasible under Food and Drug Administration Exception From Informed Consent regulations.