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Little is known about the benefit-risk profile of second-generation androgen receptor inhibitors in older men with non-metastatic castration-resistant prostate cancer. We aimed to examine the efficacy and safety of second-generation androgen receptor inhibitors in men aged 80 years or older with non-metastatic castration-resistant prostate cancer.We searched for all randomised controlled clinical trials evaluating second-generation androgen receptor inhibitors in patients with non-metastatic castration-resistant prostate cancer submitted to the US Food and Drug Administration before Aug 15, 2020, and pooled data from three trials that met the selection criteria. All three trials enrolled patients who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, castration-resistant prostate cancer, prostate-specific antigen (PSA) 2·0 μg/L or greater, PSA doubling time of 10 months or less, and no evidence of distant metastatic disease on conventional imaging per the investigator's assessment at the time of screening. All patients had histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small-cell features. All patients who were randomly assigned to androgen receptor inhibitor or placebo groups in these trials were considered assessable and were included in this pooled analysis. We evaluated the effect of age on metastasis-free survival and overall survival across age groups (80 years vs ≥80 years) in the intention-to-treat population. Safety analyses were done in patients who received at least one dose of study treatment.Between Oct 14, 2013, and March 9, 2018, 4117 patients were assigned to androgen receptor inhibitor (apalutamide, enzalutamide, or daralutamide; n=2694) or placebo (n=1423) across three randomised trials. The median follow-up duration for metastasis-free survival was 18 months (IQR 11-26) and for overall survival was 44 months (32-55). In patients aged 80 years or older (n=1023), the estimated median metastasis-free survival was 40 months (95% CI 36-41) in the androgen receptor inhibitor groups and 22 months (18-29) in the placebo groups (adjusted hazard ratio [HR] 0·37 [95% CI 0·28-0·47]), and the median overall survival was 54 months (50-61) versus 49 months (43-58), respectively (adjusted HR 0·79 [0·64-0·98]). In patients younger than 80 years of age (n=3094), the estimated median metastasis-free survival was 41 months (95% CI 36-not estimable [NE]) in the androgen receptor inhibitor groups and 16 months (15-18) in the placebo groups (adjusted HR 0·31 [95% CI 0·27-0·35]), and the median overall survival was 74 months (74-NE) versus 61 months (56-NE), respectively (adjusted HR 0·69 [0·60-0·80]). In patients aged 80 years or older, grade 3 or worse adverse events were reported in 371 (55%) of 672 patients in the androgen receptor inhibitor groups and 140 (41%) of 344 patients in the placebo groups, compared with 878 (44%) of 2015 patients in the androgen receptor inhibitor groups and 321 (30%) of 1073 patients in the placebo groups among patients younger than 80 years. The most common grade 3-4 adverse events were hypertension (168 [8%] of 2015 patients aged80 years and 51 [8%] of 672 patients aged ≥80 years in the androgen receptor inhibitor groups vs 53 [5%] of 1073 patients aged80 years and 22 [6%] of 344 patients aged ≥80 years in the placebo groups) and fracture (61 [3%] and 36 [5%] in the androgen receptor inhibitor groups vs 15 [1%] and 11 [3%] in the placebo groups).The findings of this pooled analysis support the use of androgen receptor inhibitors in older men with non-metastatic castration-resistant prostate cancer. Incorporating geriatric assessment tools in the care of older adults with non-metastatic castration-resistant prostate cancer might help clinicians to offer individualised treatment to each patient.None.

Risks of handheld electrical weapons include head impact trauma associated with uncontrolled falls, ocular probe penetration injuries, thermal injuries from the ignition of volatile fumes, and weapon confusion police-involved shooting. There is also an uncommon but critical risk of a shooting after a subject gained control of an officer’s electrical weapons. The authors searched for police shooting incidents involving loss of control of TASER® weapons via open-source media reports, crowd-sourced internet sites, litigation filings, and a survey of Axon law-enforcement master instructors. The authors report 131 incidents of subjects attempting to or gaining control of an officer’s electrical weapon from 2004 to 2020, 53 of which resulting in a shooting. These incidents demonstrated a risk of 11.8 shootings per million electrical weapon discharges (95% confidence limits of 9.0 to 15.1 per million by Wilson score interval). The use of electrical weapons presents a rare but real risk of injury and death from a shooting following a subject’s attempts to gain control of the weapon.

Background Older adults presenting to the emergency department (ED) represent a highly vulnerable patient population with complex conditions and multiple comorbidities. The introduction of a Geriatric and Palliative (GAP)-ED partnership may be an effective strategy to avoid unneeded admissions and improve outcomes for this population. Objectives The primary objective was to decrease 30-day revisit and hospitalization rates in this population through identifying patients that could be safely sent home with connection to community resources. Secondary outcomes included achieving high patient and family satisfaction scores assessed through follow-up interviews. Methods The GAP-ED intervention included the placement of a Specialist in the ED to coordinate care for older adults presenting to the ED who were likely to be discharged home. Independent t-tests and chi-squared tests were used to assess for changes in outcomes between the intervention group and a blocked matched historical usual-care group. Results There was no significant difference in 30-day ED revisits between the two groups, but there was a statistically significant reduction in hospital admissions from these 30-day revisits. Patient and family satisfaction with the presence of the GAP-ED Specialist was high. Conclusion The implementation of a GAP-ED partnership and use of a GAP-ED Specialist is an effective means of reducing hospitalization in older adults revisiting the ED.

Purpose While generally reducing morbidity and mortality, TASER® electrical weapons have risks associated with their usage, including burn injuries and head and cervical trauma associated with uncontrolled falls. The primary non-fatal complications appear to be significant eye injury but no analysis of the mechanisms or suggested treatments has been published. Methods We used a biomechanical model to predict the risk of eye injury as a function of distance from the weapon muzzle to the eye. We compared our model results to recently published epidemiological findings. We also describe the typical presentation and suggest treatment options. Results The globe rupture model predicted that a globe rupture can be expected (50% risk) when the eye is within 6 m of the muzzle and decreases rapidly beyond that. This critical distance is 9 m for lens and retinal damage which is approximately the range of the most common probe cartridges. Beyond 9 m, hyphema is expected along with a perforation by the dart portion of the probe. Our prediction of globe rupture out to 6 m (out of a typical range of 9 m) is consistent with the published risk of enucleation or unilateral blindness being 69 ± 18%, with an eye penetration. Conclusions Significant eye injury is expected from a penetration by an electrical weapon probe at close range. The risk decreases rapidly at extended distances from the muzzle. Not all penetrating globe injuries from electrical weapon probes will result in blindness.

Background Acquired thrombophilia is a potential sequela of malignancy, chronic inflammation, and conditions characterized by severe protein deficiency (for example, nephrotic syndrome, protein-losing enteropathy). As such, venous thrombosis is often a feature, and occasionally a presenting sign, of systemic disease. Ménétrier’s disease is a rare hyperplastic gastropathy that may lead to gastrointestinal protein loss and hypoalbuminemia. To date, reports of venous thrombosis associated with Ménétrier’s disease are exceedingly scarce. Case presentation We report the case of a 40-year-old white man who presented with unprovoked deep venous thrombosis, pulmonary embolism, and renal vein thrombosis. Upon receiving therapeutic anticoagulation, he developed severe gastrointestinal bleeding, and endoscopic evaluation led to a diagnosis of Ménétrier’s disease. A laboratory workup revealed deficiency of protein C, protein S, and antithrombin III, as well as markedly elevated levels of factor VIII. He was determined to have an acquired thrombophilia as a direct result of Ménétrier’s disease. Conclusions This case describes an acquired thrombophilic state in a patient with Ménétrier’s disease and profound hypoalbuminemia. Although this association is rarely described, we discuss the probable mechanisms leading to our patient’s thrombosis. Specifically, we posit that his gastrointestinal protein loss led to a deficiency of several anticoagulant proteins and a compensatory elevation in factor VIII, as occurs in nephrotic syndrome and inflammatory bowel disease. Of note, this patient’s recurrent venous thrombosis was the initial clinical sign of his gastrointestinal pathology.

Anterior crown fractures are a common form of traumatic dental injuries that mainly affect the maxillary incisors especially in children and adolescents. Complicated crown fractures although less common can be a challenging task to the clinician. Since the development of adhesive dentistry, the patient's own broken tooth fragment can be used to restore the fractured tooth. Reattachment of fractured tooth fragments with fiber postreinforcement offers a viable restorative alternative. Such procedure is economical and needs less chair-side time as compared to many traditional methods. In addition, the procedure provides good and long-lasting esthetics, as the original morphology, color, and surface texture are preserved. The main objective while treating such cases is successful pain management and immediate restoration of function, esthetics and phonetics. This paper presents a report of two cases of coronal tooth fracture that is successfully managed using tooth fragment reattachment.

Mitochondria import about 1000 proteins that are produced as precursors on cytosolic ribosomes. Defects in mitochondrial protein import result in the accumulation of non-imported precursor proteins and proteotoxic stress. The cell is equipped with different quality control mechanisms to monitor protein transport into mitochondria. First, molecular chaperones guide unfolded proteins to mitochondria and deliver non-imported proteins to proteasomal degradation. Second, quality control factors remove translocation stalled precursor proteins from protein translocases. Third, protein translocases monitor protein sorting to mitochondrial subcompartments. Fourth, AAA proteases of the mitochondrial subcompartments remove mislocalized or unassembled proteins. Finally, impaired efficiency of protein transport is an important sensor for mitochondrial dysfunction and causes the induction of cellular stress responses, which could eventually result in the removal of the defective mitochondria by mitophagy. In this review, we summarize our current understanding of quality control mechanisms that govern mitochondrial protein transport.

Objective Equipment necessary to perform pediatric microlaryngoscopy/bronchoscopy (MLB) varies considerably depending on the selected interventions. In procedures with equipment variability, surgical case length may be increased due to the need to procure items intraoperatively. We hypothesized that use of standardized huddle tools listing necessary equipment would be associated with a shortened case duration in MLB. Methods As part of a quality improvement initiative at our academic, tertiary care pediatric hospital, a standardized huddle sheet was created that listed options of equipment for MLB. Listed items included telescope/bronchoscope size, laryngoscope selection, interventional equipment, suspension, microscopes, and topical medications. The tool was completed by otolaryngology and shared with the circulating nurse at the beginning of the day so equipment needs could be anticipated. The tool was introduced to staff in November 2017 and to trainees in February 2018. To assess intervention impact, monthly median surgical case duration and room turnover time were retrospectively tracked using control chart analysis from March, 2017 to June 2019. Results At baseline, the centerline case duration was 49 minutes. Two months following introduction of the huddle sheet to trainees, the centerline duration decreased to 43 minutes. This change was sustained throughout the period studied. No changes in room turnover time were observed during this period. Conclusions Standardized huddle tool use prior to MLB was associated with a median decrease of six minutes of operating room time without a change in operating room turnover time. Use of similar tools in procedures with significant equipment variability may be beneficial.

Introduction: Our study aimed to determine 1) the association between time spent in the emergency department (ED) hallway and the development of delirium and 2) the hospital location of delirium development. Methods: This single-center, retrospective chart review included patients 18+ years old admitted to the hospital after presenting, without baseline cognitive impairment, to the ED in 2018. We identified the Delirium group by the following: key words describing delirium; orders for psychotropics, special observation, and restraints; or documented positive Confusion Assessment Method (CAM) screen. The Control group included patients not meeting delirium criteria. We used a multivariable logistic regression model, while adjusting for confounders, to assess the odds of delirium development associated with percentage of ED LOS spent in the hallway. Results: A total of 25,156 patients met inclusion criteria with 1920 (7.6%) meeting delirium criteria. Delirium group vs. Control group patients spent a greater percentage of time in the ED hallway (median 50.5% vs 10.8%, P

The US Food and Drug Administration (FDA) has approved multiple systemic vascular endothelial growth factor (VEGF) inhibitors since 2004 to treat various malignancies. Inhibition of the VEGF signaling pathway can result in impairment of vascular wall integrity through medial degeneration and endothelial dysfunction, potentially resulting in arterial (including aortic) aneurysm/dissection. We performed a postmarketing review to evaluate arterial aneurysm/dissection as a potential safety risk for patients with cancer treated with VEGF inhibitors. We searched the FDA Adverse Event Reporting System (FAERS) database and literature for reports of arterial (including aortic) aneurysm/dissection with VEGF inhibitors currently approved by the FDA for a cancer indication. We identified 240 cases of arterial aneurysm/dissection associated with VEGF inhibitors. The median time to onset of an arterial aneurysm/dissection event from the initiation of a VEGF inhibitor was 94 days (range 1–1955 days). Notably, 22% (53/240) of cases reported fatal outcomes related to arterial aneurysm/dissection. We determined the drug–event association as probable in 15 cases that lacked relevant confounding factors for arterial aneurysm/dissection, which is supported by unremarkable computed tomography (CT) findings prior to starting VEGF inhibitor therapy, despite nondrug-associated background arterial aneurysm/dissection generally demonstrating preexisting arterial abnormalities. FAERS and literature case-level evidence suggests that VEGF inhibitors may have contributed to arterial aneurysm/dissection, as a class effect, based on short onset relative to natural history of disease and biologic plausibility. Cardiovascular and oncology healthcare professionals should be aware of this rare, but life-threatening safety risk associated with VEGF inhibitors.

Background: Vaccination coverages need to be constantly maintained and improved with the implementation of vaccination strategies. This paper describes the development of an evidence-based tool to guide their planning and evaluation.Methods: A scoping review was performed in MEDLINE and institutional websites to search for similar available tools. A first version of the tool was developed considering review results and a four-step method used for the control and continuous improvement of processes and products, namely the Deming cycle. A panel of eight experts was then involved in a Delphi study for the finalization of the tool that was eventually discussed in a face-to-face meeting.Results: The scoping review found only one document and the first version of the tool was composed of 30 items. After the Delphi first round, 11 additional items were suggested and 5 original items amended. After the Delphi second round 41 items were eventually included. During the face-to-face meeting, 7 items were recognized as requisites for setting vaccination strategies, whereas 17 as relevant ones.Conclusions: Current public health challenges impose the need for evidence-based tools to organize effective vaccination strategies. Our tool is a first proposal which aims to reflect this focus.

Summary Background Between March and December, 2020, more than 20 000 laboratory-confirmed cases of SARS-CoV-2 infection were reported in Zambia. However, the number of SARS-CoV-2 infections is likely to be higher than the confirmed case counts because many infected people have mild or no symptoms, and limitations exist with regard to testing capacity and surveillance systems in Zambia. We aimed to estimate SARS-CoV-2 prevalence in six districts of Zambia in July, 2020, using a population-based household survey. Methods Between July 4 and July 27, 2020, we did a cross-sectional cluster-sample survey of households in six districts of Zambia. Within each district, 16 standardised enumeration areas were randomly selected as primary sampling units using probability proportional to size. 20 households from each standardised enumeration area were selected using simple random sampling. All members of selected households were eligible to participate. Consenting participants completed a questionnaire and were tested for SARS-CoV-2 infection using real-time PCR (rtPCR) and anti-SARS-CoV-2 antibodies using ELISA. Prevalence estimates, adjusted for the survey design, were calculated for each diagnostic test separately, and combined. We applied the prevalence estimates to census population projections for each district to derive the estimated number of SARS-CoV-2 infections. Findings Overall, 4258 people from 1866 households participated in the study. The median age of participants was 18·2 years (IQR 7·7–31·4) and 50·6% of participants were female. SARS-CoV-2 prevalence for the combined measure was 10·6% (95% CI 7·3–13·9). The rtPCR-positive prevalence was 7·6% (4·7–10·6) and ELISA-positive prevalence was 2·1% (1·1–3·1). An estimated 454 708 SARS-CoV-2 infections (95% CI 312 705–596 713) occurred in the six districts between March and July, 2020, compared with 4917 laboratory-confirmed cases reported in official statistics from the Zambia National Public Health Institute. Interpretation The estimated number of SARS-CoV-2 infections was much higher than the number of reported cases in six districts in Zambia. The high rtPCR-positive SARS-CoV-2 prevalence was consistent with observed community transmission during the study period. The low ELISA-positive SARS-CoV-2 prevalence might be associated with mitigation measures instituted after initial cases were reported in March, 2020. Zambia should monitor patterns of SARS-CoV-2 prevalence and promote measures that can reduce transmission. Funding US Centers for Disease Control and Prevention.

Study objective The objective of this study was to describe the proportion of female authors on original research articles and editorials across 4 emergency medicine journals from 2013 to 2019. A secondary objective was to examine the gender composition of middle authors in relation to the genders of their respective first and last authors. Methods In this observational study, we selected 4 journals in emergency medicine using the Journal of Citation Reports and prior literature to analyze genders of all authors from research articles and editorials published from January 2013 to September 2019. Reviewers identified author genders through web searches with matching academic qualifications or used a gender identification application programming interface to identify likelihood of male or female identity. The primary outcome was the proportion of female authors in each position. Results Selected publications included 2,980 original research articles with 18,224 authors (median 6, interquartile range [IQR] 4 to 8) and 433 editorials with 986 authors (median 2, IQR 1 to 2). Women occupied 34.9%, 24.3%, and 36.5% of first, last, and middle author positions on original research articles and 23.8%, 20.5%, and 34.2% of first, last, and middle author positions among editorials, respectively. Publications with female first and last authors (n=340 articles) had a larger proportion of female middle authors (49%, 634/1,290) compared to publications with male first and last authors (n=1667 articles, female middle authors 33% [2,215/6,771]). Conclusion Over the 7 years examined, female authorship in these emergency medicine journals increased. A more pronounced gender gap exists in editorial authorship compared to research articles. On publications where the first and last author were women, a higher proportion of middle authors were women.

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.

OBJECTIVES Sudden cardiac arrest is a leading cause of death in athletes. Although athletes wear various athletic chest protectors (ACPs) to prevent commotio cordis (CC), cardiac arrest cases still occur. Although it is established that cardiopulmonary resuscitation (CPR) quality affects outcome, little research has evaluated the effect of ACPs on CPR compressions quality. This study aimed to observe whether: (1) ACPs impact depth, rate, and hand positioning of both bystander and LUCAS CPR. (2) LUCAS devices affect CPR performance compared with traditional compressions. METHODS An observational, prospective, convenient sample of 26 emergency medicine residents performed CPR on a high-fidelity Laerdal mannequin, which recorded real-time performance data. Baseline CPR for 1- and 2-minute cycles, CPR on a mannequin wearing the ACP, and ACP removal time was recorded. LUCAS CPR performance was measured at baseline and over the ACP. RESULTS Bystander CPR had a statistically significant difference in both hand placement and compression rate for baseline versus ACP compressions (85% vs 57%, P < 0.05; 138 vs 142, P < 0.05, respectively), but not in compression depth (51.08 vs 50.05 mm, P = 0.39). LUCAS CPR had no significant difference in CPR performance. Bystander versus LUCAS CPR had a significant difference in compression rate (138 vs 101, P < 0.01), but not in depth or hand placement. CONCLUSIONS Athletic chest protectors significantly impacted hand placement during bystander CPR, which may diminish CPR quality. Considering ACP removal required only 5.4 seconds, removing the ACP before standard CPR may improve quality.

This article looks at the relationships between internet searches for unemployment-related terms, unemployment insurance (UI), and the public health orders issued in the U.S. during the Covid-19 pandemic. We find that Google searches for unemployment-related subjects surged before the record increase in initial UI claims, which in turn peaked before the public health orders were implemented. As of mid-April 2020, these orders covered the vast majority of the U.S. population. Since then, the rates of increase in both search activity and initial UI claims have slowed.

Activation of the PI3K–AKT signaling cascade is a common critical event during malignant transformation. In this study, we used thyroid gland epithelial cells and a series of genetically engineered mouse strains as model systems to demonstrate that, although necessary, AKT activation is not sufficient for PI3K-driven transformation. Instead, transformation requires the activity of the PDK1-regulated AGC family of protein kinases. In particular, SGK1 was found to be essential for proliferation and survival of thyroid cancer cells harboring PI3K-activating mutations. Notably, cotargeting SGK1 and AKT resulted in significantly higher growth suppression than inhibiting either PI3K or AKT alone. Overall, these findings underscore the clinical relevance of AKT-independent pathways in tumors driven by genetic lesions targeting the PI3K cascade. Cancer Res; 77(24); 6914–26. ©2017 AACR.

Patient: Female, 24 Final Diagnosis: Mucinous ovarian adenocarcinoma Symptoms: Nonproductive cough • shortness of breath with exertion Medication: — Clinical Procedure: — Specialty: Oncology Objective: Rare co-existance of disease or pathology Background: Mucinous ovarian adenocarcinoma is one of the less common epithelial cancers of the ovaries, and typically does not occur in younger women. Nearly all mucinous ovarian adenocarcinomas present with early-stage disease without significant sequelae of cancer, such as clotting. Anchoring bias is a common problem in medicine that has been shown to significantly affect physician decision-making. Case Report: We present the case of a 24-year-old healthy female Chinese immigrant with no significant past medical history, who presented with a subacute history of nonproductive cough and shortness of breath with exertion. Initial workup was directed towards diagnosis of tuberculosis and other infectious etiologies due to anchoring to patient’s nationality and her positive family history for tuberculosis. She was eventually diagnosed with extensive bilateral pulmonary emboli and bilateral deep vein thromboses as well as a right ventricular thrombus. This extensive clot burden helped lead to the diagnosis of mucinous ovarian adenocarcinoma. Conclusions: This case is significant not only because the diagnosis of mucinous ovarian adenocarcinoma is uncommon in healthy young females under the age of 25, but, more importantly, because such extensive pulmonary emboli and deep vein thromboses in a young female with local/early-stage ovarian cancer is very rare. This case is also significant because it serves as an important reminder of the risks of anchoring bias in skewing perceptions and delaying the correct diagnosis by physicians.

Highly infectious diseases can spread rapidly across borders through travel or trade, and international coordination is essential to a prompt and efficient response by public health laboratories. Therefore, developing strategies to identify priorities for a rational allocation of resources for research and surveillance has been the focus of a large body of research in recent years. This paper describes the activities and the strategy used by a European-wide consortium funded by the European Commission, named EMERGE (Efficient response to highly dangerous and emerging pathogens at EU level), for the selection of high-threat pathogens with cross-border potential that will become the focus of its preparedness activities. The approach used is based on an objective scoring system, a close collaboration with other networks dealing with highly infection diseases, and a diagnostic gaps analysis. The result is a tool that is simple, objective and adaptable, which will be used periodically to re-evaluate activities and priorities, representing a step forward towards a better response to infectious disease emergencies.

The FDA has approved three androgen receptor inhibitors—enzalutamide, apalutamide, and darolutamide—for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). These approvals were all based on randomized, double blind, placebo-controlled trials demonstrating large improvements in metastasis-free survival (MFS) and internally consistent evidence of benefit seen across secondary endpoints. In this article, we summarize the FDA regulatory history of MFS and we describe the design, conduct, and results of the three pivotal trials supporting these important treatment options for patients with nmCRPC.

American Indians face pervasive trauma exposure, collective histories of communal suffering, and elevated risk for depression and posttraumatic stress disorder. In addition to socioeconomic barriers, access to culturally responsive treatment is limited, which may compromise treatment engagement. The Iwankapiya study piloted the Historical Trauma and Unresolved Grief Intervention (HTUG), combined with Group Interpersonal Psychotherapy (IPT), to reduce symptoms of depression and related trauma and grief. The study hypothesized that HTUG + IPT would lead to greater group engagement and decreased depression and related symptoms compared with IPT-Only. American Indian adults (n = 52) were randomized into one of two 12-session interventions, HTUG + IPT or IPT-Only, at two tribal sites: one Northern Plains reservation (n = 26) and one Southwest urban clinic (n = 26). Standardized measures assessed depression, posttraumatic stress disorder, grief, trauma, and substance use. Data were collected at screening, baseline, end of intervention, and 8 weeks postintervention; depression and group engagement measures were also collected at Weeks 4 and 8 of the intervention. Depression scores significantly decreased for both treatments, but there were no significant differences in depression between the two groups: IPT-Only (30.2 ± 6.4 at baseline to 16.7 ± 12.1 at follow-up) and HTUG + IPT (30.2 ± 8.1 at baseline to 19.9 ± 8.8 at follow-up). However, HTUG + IPT participants demonstrated significantly greater group engagement. Postintervention, clinicians expressed preference for HTUG + IPT based upon qualitative observations of greater perceived gains among participants. Given the degree of trauma exposure in tribal communities, these findings in a relatively small sample suggest HTUG should be further examined in context of treatment engagement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective A 12-lead electrocardiogram (ECG) is the standard of care for chest pain patients. However, 12-lead ECGs have difficulty detecting ischemia of the right ventricle or posterior wall of the heart. New technology exists to mathematically synthesize these leads from a 12-lead ECG; however, this technology has not been evaluated in the emergency department (ED). We assessed the level of agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations, ST depressions, and T wave inversions in ED patients. Methods Actual 12- and 18-lead ECGs were acquired and synthesized 18-lead ECGs were produced based on waveforms from 12-lead ECGs. A blinded cardiologist interpreted the actual and synthesized 18-lead ECGs to identify the presence of abnormalities. Using actual 18-lead ECGs as the reference, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of synthesized 18-lead ECGs in identifying abnormalities were determined. Results Data from 295 patients were analyzed. There was 100% agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations and ST depressions (sensitivity, specificity, PPV, and NPV of 100%, and kappa of 1.00). Synthesized 18-lead ECGs had 95% sensitivity, 80% specificity, 97% PPV, and 70% NPV in identifying T wave inversions, when compared with actual 18-lead ECGs (kappa: 0.70). Conclusion Synthesized 18-lead ECGs demonstrated 100% agreement with actual 18-lead ECGs in the identification of ST elevations and ST depressions and good agreement in the identification of T wave inversions in a sample of patients ED patients with complaints suspicious of cardiac origin.

PURPOSE To assess the relationship among tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti–programmed death protein 1 or ligand 1 (anti–PD-1/L1) antibodies. PATIENTS AND METHODS We examined seven trials in 1,747 patients with metastatic or locally advanced urothelial cancer that led to approval of an anti–PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy, and two enrolled patients who were cisplatin ineligible. The data sets were searched for AESIs, related AESIs, imAEs, and related imAEs. The relationship to study drug was determined by the investigator. ImAEs were defined as AESIs treated with topical or systemic corticosteroids. RESULTS In these exploratory analyses, a related AESI was reported in 64% of responding patients and in 34% of patients who did not respond to the anti–PD-1/L1 antibody, whereas a related imAE occurred in 28% and 12% of patients who did and did not respond to study drug, respectively. In a responder analysis, an increase in overall survival was seen in patients with related AESIs compared with those with no related AESIs (hazard ratio, 0.45; 95% CI, 0.39 to 0.52). Fifty-seven percent of responding patients with a related AESI reported the AESI before documentation of response. CONCLUSION Patients who responded to treatment with an anti–PD-1/L1 antibody were more likely to report a related AESI or related imAE. This relationship did not seem to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.

Background Long-term sustainability of successful improvement initiatives remains a pragmatic challenge with limited literature guidance. A chronic obstructive pulmonary disease (COPD) care bundle was developed and implemented to mitigate care-delivery failures and unmet patient needs at University of Cincinnati Medical Center that led to a 35% reduction in 30-day all-cause readmissions. Here, two-year outcomes and the method of achieving sustainability are presented. Methods After implementation of the COPD care bundle, 30-day all-cause readmissions reduced from 22.7% to 14.7%. In 2016 the project transitioned from implementation to the sustainability phase. A four-member sustainability team was formed (pulmonologist, hospitalist, respiratory therapist, and pharmacist) with clearly defined roles for monitoring and facilitating sustainability actions. The process of bundle delivery was purposefully designed for higher reliability. Staff education and daily operations were updated to incorporate the new process. Outcome (readmission rate) and process (bundle adherence) measures were monitored monthly. Any significant drop (special cause variation) would be reviewed by the team and further action taken, if needed. The National Health Service sustainability model was used, with adjustments made to meet our contextual needs. Results The 30-day all-cause readmission rate remained the same as during the initial implementation phase (14.9%). Adherence to COPD care bundle components was 87.7%. During the two-year period, three occasions triggered a team discussion and detailed review. Conclusion Sustainability requires a purposefully designed, resilient process; standard work; engagement of the team and leadership; and a monitoring system of key process and outcome measures. Application of sustainability models should be adjusted for specific contextual needs.

4559 Background: The International Metastatic RCC Database Consortium (IMDC) risk model was developed for prognosis of patients with mRCC treated with vascular endothelial growth factor (VEGF)-targeted monotherapy in the first-line setting. Efficacy in trials of anti-VEGF therapy has been generally consistent across risk groups, including for overall survival (OS). For trials of immunotherapy combinations, the small numbers of OS events for the favorable risk group in each trial limited reliable conclusions; however, there was a suggestion of possible differential effects on OS between favorable risk and other risk groups. Methods: We pooled individual patient data (n=3447) from four phase III randomized trials of combinations of immunotherapy + immunotherapy (n=1) or immunotherapy + anti-VEGF therapy (n=3) submitted to the US Food and Drug Administration in support of marketing applications. All trials calculated IMDC risk group for each patient and used a control arm of sunitinib. We combined intermediate and poor prognostic groups (“intermediate/poor”) and compared their OS to that of the favorable risk group using Kaplan-Meier and Cox Proportional Hazards methods. Results: In this pooled analysis, treatment with combination immune checkpoint therapy did not demonstrate an improvement in OS compared to sunitinib in the favorable risk group (HR 0.953; 95% CI: 0.72, 1.27). An improvement in OS was observed in the intermediate/poor risk group (HR 0.696; 95% CI: 0.62, 0.78). Conclusions: Our analysis of OS in patients treated with immunotherapy combinations compared to sunitinib suggests possible differential benefit in the favorable risk compared to the intermediate/poor risk group. These results are not conclusive and considered exploratory due to the relative immaturity of OS in the favorable risk group. Follow-up for survival continues in each study to allow for more definitive results.[Table: see text]

Background Mitosis is a process of cell division resulting in two genetically equivalent daughter cells. Excessive proliferation of cells due to mitosis is the hallmark in pre cancer and cancer. Aims This study was conducted to count the number of mitotic figures in normal oral mucosa, oral epithelial dysplasia and squamous cell carcinoma in both Hematoxylin and Eosin (H&E) and Crystal Violet stained sections. Also the overall number of mitotic figures with both stains were compared along with the evaluation of staining efficacy of both the stains. Methods and material The present study was conducted on 20 specimens each of the three categories. These were further divided into two groups for staining with H&E and with 1% Crystal Violet respectively. Images were captured and analyzed using image analysis software Dewinter Biowizard 4.1. Results Comparison of mitotic figure count in three categories in sections stained with both stains showed statistically significant difference (p Conclusion Number of mitotic figures progressively increase with the advancement of the pathology. Use of 1% Crystal Violet provides better appreciation of mitotic figures and can be employed as a selective stain in routine histopathology.

12038 Background: The FDA has approved three androgen receptor (AR) inhibitors for nonmetastatic castration-resistant prostate cancer (nmCRPC) based on improvements in metastasis-free survival (MFS). MFS is an earlier endpoint, defined as the time from randomization to either imaging-detectable distant disease or death. This pooled analysis examines MFS, time to initiation of cytotoxic chemotherapy (TTCyto), and safety outcomes in men over 80 treated with AR inhibitors. Methods: Data was pooled from three randomized controlled studies (n=4117) of AR inhibitors for nmCRPC. The treatment effect of AR inhibitors on MFS and TTCyto across age groups was evaluated using Kaplan-Meier estimates and a Cox proportional hazards regression model. Hazard Ratios for MFS and TTCyto were adjusted for baseline ECOG, total Gleason score, PSA doubling time, and prior bone-targeting therapy. Results: For patients age 80 years or older (n=675) who were treated with AR inhibitors, the hazard ratio was 0.38 (95% CI 0.29, 0.49) with an estimated median MFS of 40 months (95% CI 36, 41) versus 22 months (95% CI 18, 29) for those treated with placebo (n=348). For patients

5045 Background: Although recent evidence has suggested that patients who receive antibiotics (ABX) during the course of ICI treatment might decrease overall survival (OS) (1), our previous analysis did not support a difference in OS in urothelial cancer patients who did and did not use ABX during the course of ICI treatment without regard to timing (2). This updated analysis aims to addresses the question of timing; specifically, use of ABX in the 30-day window pre- or post- initiation of ICI treatment. Methods: We pooled data from 7 trials that led to drug approval and which included 1747 patients with advanced urothelial cancer treated with an ICI. Five trials enrolled patients who received prior platinum and 2 enrolled cisplatin-ineligible patients. Concomitant medication datasets were searched for systemic ABX use. The association between ABX use and survival was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression models stratified by study. Results: Overall, 56% of patients were exposed to antibiotics (ABX+) and 43% were not exposed (ABX-). In an exploratory analysis, median OS was similar between arms: 9.7 vs. 9.3 months in ABX+ vs. ABX- patients, respectively (HR 0.96). However, OS results differed in the 27% of patients who were exposed to antibiotics in the 30-day window pre- or post- initiation of ICI treatment, for whom median OS was 4.7 months vs. 11.5 months in the ABX+ vs. ABX- patients, respectively (HR 1.8). This remained true after controlling for baseline risk prognostic factors (Bajorin and Bellmunt scores). Similar trends were observed for progression-free survival (PFS). Conclusions: Patients treated with ABX while on therapy with an ICI for urothelial cancer had similar OS outcomes to those not treated with ABX. However, in an exploratory analysis looking at ABX use in the 30-day window pre- or post-initiation of ICI treatment, OS appeared decreased in ABX+ vs ABX- patients. Our exploratory analyses appear to show an association of OS/PFS with timing of antibiotics. References: 1) Routy B, Science (2017) 2) Weinstock C, ASCO 2019, abstract. [Table: see text]

Background: The quality of antenatal care (ANC) a woman receives during pregnancy is crucial to both the child and the mother’s life. It has been established that providing high-quality ANC can save lives and has a positive impact on postnatal health care services. However, the quality of ANC in Zambia requires attention as maternal and neonatal mortality rates are still unacceptably high with Lusaka district not being left out of the problem. Methods: Using a cross-sectional study design, the main aim of this study was to determine the demand side factors associated with high-quality antenatal care among pregnant women in Lusaka. It also estimated the proportion of women who received high-quality ANC during their last antenatal visit. Multifactorial logistic regression model was fitted in STATA version 13 to predict the demographic, socio and economic factors that influence the quality of ANC. Results: It was established that only 47.1% of pregnant women received high-quality ANC while 52.9% received low quality. Six key ANC interventions were considered, among which urine (36.7%) and blood (46.8%) testing were the least received basic components of ANC. After adjusting for the effect of other factors, women with secondary education had higher odds of receiving high-quality ANC than women with primary level of education (OR = 1.98; 95% CI: 1.24 to 3.14). Women staying with their husband/partners had lesser odds of receiving high quality ANC compared to those that were not staying with their partners (OR = 0.47; 95% CI: 0.28 to 0.79). Conclusion: The quality of antenatal care received by pregnant women in Lusaka is low. Continued efforts to improve the delivery of basic ANC services such as blood and urine testing is required to improve the quality of healthcare services provided by medical personnel at all levels.

In this protocol we describe the separation and visualization of ubiquitylated forms of the yeast mitofusin Fzo1 by Western blot. To this aim, we express HA-tagged Fzo1 in Saccharomyces cerevisiae, break the cells to extract a membrane-enriched fraction, solubilize the membranes using detergent and then specifically immunoprecipitate the tagged protein using anti-HA affinity beads. Subsequently, we separate the higher molecular weight (ubiquitylated) forms of Fzo1 via SDS-PAGE. Finally, immunoblotting and immunodecoration are used to detect the protein and its ubiquitylated forms using an HA-specific antibody. By using this protocol, it is possible to separate and visualize higher molecular weight forms of low abundant proteins such as Fzo1 and detect sharp and distinct bands above the unmodified protein by Western blot.

The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60–0.84). The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14–0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30–0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide. Implications for Practice: This new approval expands the enzalutamide indication, allowing health care providers and patients to use enzalutamide for the treatment of metastatic castration-resistant prostate cancer either before or after cytotoxic chemotherapy.

Tensioactive agents may alter dentinal wettability allowingincreased sealer penetration into dentinal tubules. This may improve the apical seal and better entomb remaining bacteria.The purpose of this study was to determine if a final rinse of alcohol or sodium hypochlorite increased sealer coverage of root canal. The samplcs were randomly divided into four groups according to the method of sealer placement and final irrigant used. Group 1 file and 95% ethanol, group 2 file and 5.25% sodium hypochlorite, group 3 lentulospiral and 95% ethanol, group 4 lentulospiral and 5.25% sodium hypochlorite. The samples were obturated with AH26 as sealer mixed with carbon black powder and gutta percha All samplcs were decalcitied with 5% nitric acid and dehydrated in alcohol, followed by clearing in methyl salicylate. The cleared samples were measured under dissecting microscopefor sealer penetration with the help of millimeter scale. Although a final rinse of alcohol did not increase sealer coverage, a high variability was found in the middle and apical third portions ofthe root canals.

Purpose While generally reducing morbidity and mortality, electrical weapons have risks associated with their usage, including burn injuries and trauma associated with uncontrolled fall impacts. However, the prevalence of significant eye injury has not been investigated. Methods We searched for incidents of penetrating eye injury from TASER® conducted electrical weapon (CEW) probes via open source media, litigation filings, and a survey of CEW law-enforcement master instructors. Results We report 20 previously-unpublished cases of penetrating eye injury from electrical weapon probes in law-enforcement field uses. Together with the 8 previously published cases, there are a total of 28 cases out of 3.44 million field uses, giving a demonstrated CEW field-use risk of penetrating eye injury of approximately 1:123 000. Confidence limits [85 000, 178 000] by Wilson score interval. There have been 18 cases of total unilateral blindness or enucleation. We also present legal decisions on this topic. Conclusions The use of electrical weapons presents a rare but real risk of total or partial unilateral blindness from electrical weapon probes. Catastrophic eye injuries appear to be the dominant non-fatal complication of electronic control.

Introduction—We have previously published on the ventricular fibrillation (VF) risk with TASER® X26 conducted electrical weapon (CEW). Our risk model accounted for realistic body mass index distributions, modeled the effects of partial or oblique dart penetration, and used epidemiological CEW statistics. As new CEWs have become available to law enforcement, their cardiac safety profile was not quantified. Therefore, we applied our VF probability model to evaluate their cardiac risk.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). Effective and safe adjunct antithrombotic therapy is a major determinant for short- and long-term outcomes after primary PCI. Two separate studies have shown significant benefits vs conventional therapy for 2 recently approved drugs. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors. However, during the first 24 hours after PCI, there was an increase in stent thrombosis rates with bivalirudin. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial, prasugrel was superior to clopidogrel in patients with acute coronary syndrome with and without ST-segment elevation. The synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing primary PCI. However, no specifically designed studies have so far compared the combination of prasugrel plus bivalirudin with that of clopidogrel plus unfractionated heparin in these patients. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is a randomized, open-label, multicenter trial aimed to test the hypothesis that a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus unfractionated heparin in terms of net clinical outcome in STEMI patients with planned primary PCI.