Risk of hospitalization in synucleinopathies and impact of psychosis

BackgroundFew studies have investigated the risk of hospitalization among patients with synucleinopathies (Parkinson disease, Dementia with Lewy Bodies, Parkinson disease dementia, Multiple System Atrophy) with associated psychosis and the impact of antipsychotic treatments on hospital admissions and duration of the stay.ObjectiveTo determine the risk of hospitalization among patients with synucleinopathies and in patients with associated psychosis. To evaluate the impact of antipsychotic treatments on hospital admission of patients with synucleinopathies and psychosis in an incident cohort study in Olmsted County, Minnesota (MN).MethodsWe used the Rochester Epidemiology Project (REP) to define an incident cohort of patients with clinically diagnosed synucleinopathies (1991–2010) in Olmsted County, MN. A movement disorder specialist reviewed all medical records to confirm the clinical diagnosis of synucleinopathies using the NINDS/NIMH unified diagnostic criteria.ResultsWe included 416 incident cases of clinically diagnosed synucleinopathies from 2,669 hospitalizations. 409 patients (98.3%) were admitted to the hospital at least once for any cause after the onset of parkinsonism. The median number of hospitalizations for a single patient was 5. In total, 195 (46.9%) patients met the criteria for psychosis: patients with psychosis had a 49% (HR = 1.49, p < 0.01) increased risk of hospitalization compared to patients without psychosis. Among patients with psychosis, 76 (39%) received antipsychotic medication. Treatment with antipsychotic medications did not affect the risk of hospitalization (HR = 0.93, p = 0.65). The median length of hospitalization among the entire cohort was 1 (IQR 0–4) day. There was no difference between hospitalization length for patients with no psychosis and patients with active psychosis (RR = 1.08, p = 0.43) or patients with resolved psychosis (RR = 0.79, p = 0.24).ConclusionPsychosis increases the risk of hospitalization in patients with clinically defined synucleinopathies; however, it does not affect the length of hospital stays in our cohort. Antipsychotic treatment does not affect the risk of hospitalization in our study

Clinical and kidney structural characteristics of living kidney donors with nephrolithiasis and their long-term outcomes

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function. Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (\u3e5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including review of metabolic evaluations in stone formers. Long-term risks of renal complications (low eGFR and hypertension) by stone former status were evaluated. Results: There were 12 symptomatic and 76 asymptomatic stone formers among 866 donors. Overall, baseline clinical characteristics and implantation biopsy findings were similar between stone formers and non-stone formers. After a median follow-up of 10 y, stone former status was not associated with eGFR \u3c60 mL/min/1.73 m2, eGFR \u3c45 mL/min/1.73 m Conclusions: Both asymptomatic and symptomatic SF have favorable histology findings at baseline. Long-term kidney outcomes were favorable in select stone formers with no evident increased long-term risk for decreased kidney function or hypertension after donation

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Unheard Victims: Multidisciplinary Incidence and Reporting of Violence in an Emergency Department

Introduction: Workplace violence in the emergency department (ED) is a serious threat to staff and is likely to go unreported. We sought to identify the incidence of violence among staff at our academic ED over a six-month period.Methods: An anonymous survey was sent to all ED staff, asking whether respondents had experienced verbal abuse or physical assault over the prior six months and whether they had reported it. Those working in the department <6 months were excluded from analysis. We used chi-squared comparison to analyze the results.  Results: We analyzed 242 responses. Overall, 208 (86%) respondents indicated being verbally abused in the preceding six months, and 90 (37%) indicated being physically assaulted. Security officers had the highest incidence of verbal abuse (98%), followed by nursing (95%), patient care assistants (PCA) (90%) and clinicians (90%), phlebotomists (75%), care team assistants (73%), registration staff (50%) and electrocardiogram (ECG)/radiology technicians (50%). Security also had the highest incidence of physical assault (73%), followed by nursing (49%), PCAs (30%), clinicians (24%), phlebotomists (17%), and ECG/radiology technicians (13%). A total of 140 (69%) non-security personnel indicated that they never report incidents of violence.Conclusion: Our results indicate that violence in the ED affects more than just nurses and doctors. As health systems seek to improve the safety of their employees in violence-prone areas, it is imperative that they direct initiatives to the entire healthcare team as no one group is immune

Unheard Victims: Multidisciplinary Incidence and Reporting of Violence in an Emergency Department

Introduction: Workplace violence in the emergency department (ED) is a serious threat to staff and is likely to go unreported. We sought to identify the incidence of violence among staff at our academic ED over a six-month period.Methods: An anonymous survey was sent to all ED staff, asking whether respondents had experienced verbal abuse or physical assault over the prior six months and whether they had reported it. Those working in the department <6 months were excluded from analysis. We used chi-squared comparison to analyze the results.  Results: We analyzed 242 responses. Overall, 208 (86%) respondents indicated being verbally abused in the preceding six months, and 90 (37%) indicated being physically assaulted. Security officers had the highest incidence of verbal abuse (98%), followed by nursing (95%), patient care assistants (PCA) (90%) and clinicians (90%), phlebotomists (75%), care team assistants (73%), registration staff (50%) and electrocardiogram (ECG)/radiology technicians (50%). Security also had the highest incidence of physical assault (73%), followed by nursing (49%), PCAs (30%), clinicians (24%), phlebotomists (17%), and ECG/radiology technicians (13%). A total of 140 (69%) non-security personnel indicated that they never report incidents of violence.Conclusion: Our results indicate that violence in the ED affects more than just nurses and doctors. As health systems seek to improve the safety of their employees in violence-prone areas, it is imperative that they direct initiatives to the entire healthcare team as no one group is immune

The Team Is Not Okay: Violence in Emergency Departments Across Disciplines in a Health System

Introduction: Healthcare workers, particularly those in the emergency department (ED), experience high rates of injuries caused by workplace violence (WPV).Objective: Our goal was to establish the incidence of WPV among multidisciplinary ED staff within a regional health system and assess its impact on staff victims.Methods: We conducted a survey study of all multidisciplinary ED staff at 18 Midwestern EDs encompassing a larger health system between November 18–December 31, 2020. We solicited the incidence of verbal abuse and physical assault experienced and witnessed by respondents over the prior six months, as well as its impact on staff.Results: We included responses from 814 staff (24.5% response rate) for final analysis with 585 (71.9%) indicating some form of violence experienced in the preceding six months. A total of 582 (71.5%) respondents indicated experiencing verbal abuse, and 251 (30.8%) indicated experiencing some form of physical assault. All disciplines experienced some type of verbal abuse and nearly all experienced some type of physical assault. One hundred thirty-five (21.9%) respondents indicated that being the victim of WPV has affected their ability to perform their job, and nearly half (47.6%) indicated it has changed the way they interact with or perceive patients. Additionally, 132 (21.3%) indicated experiencing symptoms of post-traumatic stress, and 18.5% reported they have considered leaving their position due to an incident.Conclusion: Emergency department staff suffer violence at a high rate, and there is no discipline that is spared. As health systems seek to prioritize staff safety in violence-prone areas such as the ED, it is imperative to recognize that the entire multidisciplinary team is impacted and requires targeted efforts for improvement in safety

Relationship between individual and country-level socio-economic background, USMLE step scores, and demographics of international medical graduates and residency match results

Abstract Purpose Twenty five percent of practicing physicians in the US are International Medical Graduates (IMGs) – physicians who completed their medical school training outside of the United States and Canada. There are multiple studies demonstrating higher socio-economic background is associated with medical school matriculation in the US. However, despite a substantial prevalence of IMGs in the American healthcare system, studies of the association between demographics, socio-economic background, and securing a residency position in the match are lacking. Methods We created a survey with questions on residency match-related data and information on personal socio-economic background. An invitation to participate in the study was sent to all IMGs that applied to the included residency programs after the conclusion of the 2022 residency match. We used multivariable logistic regression to compare survey responses to the odds of securing a residency match. Results The total number of survey respondents was 744 (response rate 15.1%). We found that younger age, higher United States Medical License Examination (USMLE) scores, higher-income country of origin (including the United States), fewer match attempts, applying to fewer specialties, having parents with college degree or higher, and coming from higher-than-average or lower-than-average family income were independently associated with increased odds of matching. Gender, personal income, and visa status did not demonstrate significant associations with residency match. Conclusions Residency match is a significant expense for IMGs, especially for those from lower-income countries. International applicants from higher socio-economic backgrounds might have advantages in securing medical residency positions in the United States when controlling for other variables

Barrier Enclosure for Endotracheal Intubation in a Simulated COVID-19 Scenario: A Crossover Study

Introduction: Barrier enclosures have been developed to reduce the risk of COVID-19 transmission to healthcare providers during intubation, but little is known about their impact on procedure performance. We sought to determine whether a barrier enclosure delays time to successful intubation by experienced airway operators.Methods: We conducted a crossover simulation study at a tertiary academic hospital. Participants watched a four-minute video, practiced one simulated intubation with a barrier enclosure, and then completed one intubation with and one without the barrier enclosure (randomized to determine order). The primary outcome measure was time from placement of the video laryngoscope at the lips to first delivered ventilation. Secondary outcomes were periprocedural complications and participant responses to a post-study survey.Results: Proceduralists (n = 50) from emergency medicine and anesthesiology had median intubation times of 23.6 seconds with practice barrier enclosure, 20.5 seconds with barrier enclosure, and 16.7 seconds with no barrier. Intubation with barrier enclosure averaged 4.5 seconds longer (95% confidence interval, 2.7-6.4, p < .001) than without, but was less than the predetermined clinical significance threshold of 10 seconds. Three complications occurred, all during the practice intubation. Barrier enclosure made intubation more challenging according to 48%, but 90% indicated they would consider using it in clinical practice.Conclusion: Experienced airway operators performed intubation using a barrier enclosure with minimal increased time to procedure completion in this uncomplicated airway model. Given potential to reduce droplet spread, use of a barrier enclosure may be an acceptable adjunct to endotracheal intubation for those familiar with its use