Updated 5-year results for short course abiraterone acetate and LHRH agonist for unfavorable intermediate and favorable high-risk prostate cancer.

Combined androgen deprivation therapy (ADT) and radiotherapy (RT) improves outcomes for intermediate and high-risk prostate cancer. Treatment intensification with abiraterone acetate/prednisone (AAP) provides additional benefit for high-risk disease. We previously reported 3-year outcomes of a single-arm prospective multicenter trial (AbiRT trial) of 33 patients with unfavorable intermediate risk (UIR) and favorable high risk (FHR) prostate cancer undergoing short course, combination therapy with ADT, AAP, and RT.

Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study.

Background: Limited responses have been observed in patients treated with enzalutamide after disease progression on abiraterone for metastatic castration-resistant prostate cancer (mCRPC), but androgen receptor signaling impacts T-cell function.

Objective: To evaluate the efficacy and safety of pembrolizumab plus enzalutamide in mCRPC.

Design, Setting, And Participants: Patients in cohort C of the phase 1b/2 KEYNOTE-365 study, who received ≥4 wk of treatment with abiraterone acetate in the prechemotherapy mCRPC state and experienced treatment failure or became drug-intolerant, were included.

Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study.

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments.

Objective: To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC.

Design, Setting, And Participants: The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening.

Examining health care champions: a mixed-methods study exploring self and peer perspectives of champions.

Background: Champions are widely recognized as playing a key role in the successful implementation of evidence-based interventions within the health care sector; however, little is known about which characteristics and skills enable them to play that role. Furthermore, previous studies have measured only individual champions' responses to personal attributes without incorporating input from other observers. A mixed-methods study was conducted to identify, analyze, and group the behaviors and characteristics of champions who have successfully promoted the adoption of new initiatives within the health care delivery system, taking into consideration self and peer perspectives.

Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide.

Purpose: While the detection of AR-V7 in circulating tumor cells (CTC) is associated with resistance to abiraterone or enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), it only accounts for a minority of this resistance. Neuroendocrine (NE) differentiation or chromosomal instability (CIN) may be additional mechanisms that mediate resistance.

Experimental Design: PROPHECY was a multicenter prospective study of men with high-risk mCRPC starting abiraterone or enzalutamide.

Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer.

Purpose: Long-term androgen-deprivation therapy (ADT) is the standard of care in combination with radiation therapy (RT) in high-risk prostate cancer (PC), despite substantial toxicity from the resulting hypogonadism. We hypothesized that a combination of more potent but shorter-term androgen inhibition in men with intermediate- or high-risk localized PC would synergize with definitive RT to provide short-term testosterone recovery and improve disease control.

Methods And Materials: This prospective phase 2 single-arm trial enrolled men with low-volume unfavorable intermediate or high-risk localized PC.

Prospective Multicenter Study of Circulating Tumor Cell AR-V7 and Taxane Versus Hormonal Treatment Outcomes in Metastatic Castration-Resistant Prostate Cancer.

Purpose: Androgen receptor splice variant 7 (AR-V7) detection in circulating tumor cells (CTCs) is associated with a low probability of response and short progression-free (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide or abiraterone. However, it is unclear whether such men benefit from taxane chemotherapy.

Patients And Methods: PROPHECY is a multicenter prospective blinded study of patients with poor-risk mCRPC starting abiraterone or enzalutamide and observed through subsequent progression and taxane chemotherapy.

Pembrolizumab in men with heavily treated metastatic castrate-resistant prostate cancer.

Background: Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)-high or mismatch repair-deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies.

Methods: We performed a single institution retrospective review of men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with pembrolizumab.

Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study.

Purpose: Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given that previous reports suggested that circulating tumor cell (CTC) AR-V7 detection is a poor prognostic indicator for the clinical efficacy of secondary hormone therapies, we conducted a prospective multicenter validation study.

Patients And Methods: PROPHECY ( ClinicalTrials.

Phase 1 study of PSMA ADC, an antibody-drug conjugate targeting prostate-specific membrane antigen, in chemotherapy-refractory prostate cancer.

Background: Prostate-specific membrane antigen (PSMA) is a well-characterized target that is overexpressed selectively on prostate cancer cells. PSMA antibody-drug conjugate (ADC) is a fully human IgG1 monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE), which is designed to specifically bind PSMA-positive cells, internalize, and then release its cytotoxic payload into the cells. PSMA ADC has demonstrated potent and selective antitumor activity in preclinical models of advanced prostate cancer.

Quality Improvement in Ambulatory Surgery Centers: A Major National Effort Aimed at Reducing Infections and Other Surgical Complications.

Background: Surgical volume has shifted significantly from inpatient to outpatient settings, including free-standing ambulatory surgery centers (ASCs). Approaches to quality improvement (QI) and surveillance used in hospitals are not always appropriate to the ambulatory setting.

Methods: We recruited 665 ASCs in 47 US states to participate in an intervention to improve safe practice through implementation of a surgical safety checklist and infection control practices.

Scaling Safety: The South Carolina Surgical Safety Checklist Experience.

Proven patient safety solutions such as the World Health Organization's Surgical Safety Checklist are challenging to implement at scale. A voluntary initiative was launched in South Carolina hospitals in 2010 to encourage use of the checklist in all operating rooms. Hospitals that reported completing implementation of the checklist in their operating rooms by 2017 had significantly higher levels of CEO and physician participation and engaged more in higher-touch activities such as in-person meetings and teamwork skills trainings than comparison hospitals did.

Phase I Study of Seviteronel, a Selective CYP17 Lyase and Androgen Receptor Inhibitor, in Men with Castration-Resistant Prostate Cancer.

Seviteronel (INO-464) is a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor (AR) inhibitor with antitumor activity and This open-label phase I clinical study evaluated the safety, tolerability, pharmacokinetics and activity of once-daily seviteronel in male chemotherapy-naïve subjects with castration-resistant prostate cancer (CRPC). Seviteronel was administered at 600 mg once daily with dose titration (DT) and in modified 3 + 3 dose escalation once-daily cohorts at 600, 750, and 900 mg without DT. The primary objectives of this study were to establish safety, tolerability, and the MTD of seviteronel in chemotherapy-naïve subjects with or without prior treatment with FDA-approved CRPC treatments, abiraterone acetate (AA), and enzalutamide.

An evidence-based intraoperative communication tool for emergency general surgery: a pilot study.

Background: Emergency general surgery (EGS) is characterized by high rates of morbidity and mortality. Though checklists and associated communication-based huddle strategies have improved outcomes, these tools have never been specifically examined in EGS. We hypothesized that use of an evidence-based communication tool aimed to trigger intraoperative discussion could improve communication in the EGS operating room (OR).

Factors associated with the use of cognitive aids in operating room crises: a cross-sectional study of US hospitals and ambulatory surgical centers.

Background: Operating room (OR) crises are high-acuity events requiring rapid, coordinated management. Medical judgment and decision-making can be compromised in stressful situations, and clinicians may not experience a crisis for many years. A cognitive aid (e.

Multisource Evaluation of Surgeon Behavior Is Associated With Malpractice Claims.

Objective: We merged direct, multisource, and systematic assessments of surgeon behavior with malpractice claims, to analyze the relationship between surgeon 360-degree reviews and malpractice history.

Background: Previous work suggests that malpractice claims are associated with a poor physician-patient relationship, which is likely related to behaviors captured by 360-degree review. We hypothesize that 360-degree review results are associated with malpractice claims.

Developing Process Maps as a Tool for a Surgical Infection Prevention Quality Improvement Initiative in Resource-Constrained Settings.

Background: Surgical infections cause substantial morbidity and mortality in low-and middle-income countries (LMICs). To improve adherence to critical perioperative infection prevention standards, we developed Clean Cut, a checklist-based quality improvement program to improve compliance with best practices. We hypothesized that process mapping infection prevention activities can help clinicians identify strategies for improving surgical safety.

Mortality Trends After a Voluntary Checklist-based Surgical Safety Collaborative.

Objective: To determine whether completion of a voluntary, checklist-based surgical quality improvement program is associated with reduced 30-day postoperative mortality.

Background: Despite evidence of efficacy of team-based surgical safety checklists in improving perioperative outcomes in research trials, effective methods of population-based implementation have been lacking. The Safe Surgery 2015 South Carolina program was designed to foster state-wide engagement of hospitals in a voluntary, collaborative implementation of a checklist program.

Relationship Between Labor and Delivery Unit Management Practices and Maternal Outcomes.

Objective: To define, measure, and characterize key competencies of managing labor and delivery units in the United States and assess the associations between unit management and maternal outcomes.

Methods: We developed and administered a management measurement instrument using structured telephone interviews with both the primary nurse and physician managers at 53 diverse hospitals across the United States. A trained interviewer scored the managers' interview responses based on management practices that ranged from most reactive (lowest scores) to most proactive (highest scores).

Perception of Safety of Surgical Practice Among Operating Room Personnel From Survey Data Is Associated With All-cause 30-day Postoperative Death Rate in South Carolina.

Objective: To evaluate whether the perception of safety of surgical practice among operating room (OR) personnel is associated with hospital-level 30-day postoperative death.

Background: The relationship between improvements in the safety of surgical practice and benefits to postoperative outcomes has not been demonstrated empirically.

Methods: As part of the Safe Surgery 2015: South Carolina initiative, a baseline survey measuring the perception of safety of surgical practice among OR personnel was completed.

Narrative feedback from OR personnel about the safety of their surgical practice before and after a surgical safety checklist intervention.

Objective: To examine narrative feedback to understand surgical team perceptions about surgical safety checklists (SSCs) and their impact on the safety of surgical practice.

Design: We reviewed free-text comments from surveys administered before and after SSC implementation between 2011 and 2013. We categorized feedback thematically and as positive, negative or neutral.

Implementation of the World Health Organization Trauma Care Checklist Program in 11 Centers Across Multiple Economic Strata: Effect on Care Process Measures.

Background: Trauma contributes more than ten percent of the global burden of disease. Initial assessment and resuscitation of trauma patients often requires rapid diagnosis and management of multiple concurrent complex conditions, and errors are common. We investigated whether implementing a trauma care checklist would improve care for injured patients in low-, middle-, and high-income countries.

Postoperative acute care use after freestanding ambulatory surgery.

Background: Surgical procedures in the United States are increasingly performed in the ambulatory setting, including freestanding ambulatory surgery centers (ASCs). However, there is a lack of research and tracking of surgical outcomes in this setting.

Materials And Methods: We analyzed data from a state all-payer claims database to produce a retrospective cohort study on the rate of acute care use (emergency department [ED] visits and inpatient admissions) within 7 d after operations performed in freestanding ASCs in South Carolina.