US Food and Drug Administration Approval Summary: Talazoparib in Combination With Enzalutamide for Treatment of Patients With Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer.

Purpose: The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially: an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2).

FDA Approval Summary: Olaparib in Combination With Abiraterone for Treatment of Patients With -Mutated Metastatic Castration-Resistant Prostate Cancer.

Purpose: This article summarizes the US Food and Drug Administration (FDA) review of the data leading to approval of olaparib plus abiraterone for the treatment of patients with deleterious or suspected deleterious -mutated (m) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.

Patients And Methods: Approval was based on the results from PROpel, a double-blind trial that randomly assigned 796 patients with mCRPC to abiraterone plus prednisone or prednisolone with either olaparib or placebo. The primary end point was radiographic progression-free survival (rPFS) per investigator assessment.

Do Saliva-Saturated Spit Hoods Interfere With Ventilation?

Spit hoods are used by law enforcement, officers in correctional facilities, and medical personnel during the restraint of agitated subjects that are actively spitting to prevent the transmission of droplet-transmitted pathogens. We could find no studies reporting on the time course of normal breathing to clear saliva from such a saturated spit hood. We purchased samples of 3 popular spit hood models and applied a section over the output of a pneumatic test system.

A U.S. Food and Drug Administration-pooled Analysis of Frontline Combination Treatment Survival Benefits by Risk Groups in Metastatic Renal Cell Carcinoma.

Background: While frontline immuno-oncology/tyrosine kinase inhibitor (IO/TKI) combination therapy has established a benefit in metastatic renal cell carcinoma (mRCC), this may differ by International Metastatic RCC Database Consortium (IMDC) risk grouping. Looking at individual trials, we noted an apparently smaller magnitude of benefit for favorable-risk disease.

Objective: We aimed to assess treatment benefit by risk groupings, especially in favorable-risk, augmenting patient numbers via a pooled analysis.

FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease-Associated Tumors.

On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET.

Confusion between firearms and electrical weapons as a factor in police shootings.

Conducted electrical weapons (CEW) have risks including trauma associated with uncontrolled falls, probes penetrating the eye, and fume ignition. A lesser-known risk is weapon-confusion error with officers mistakenly discharging their firearm when they intended to deploy their electrical weapon. We searched for incidents of possible weapon confusion with the TASER® brand CEWs via open-source media, litigation filings, and a survey of CEW law enforcement master instructors.

Output of Electronic Muscle Stimulators: Physical Therapy and Police Models Compared.

Introduction: Both physical therapists and police officers use electrical muscle stimulation. The typical physical therapist unit is attached with adhesive patches while the police models use needle-based electrodes to penetrate clothing. There have been very few papers describing the outputs of these physical therapy EMS (electrical muscle stimulator) units.

Detection of Arcing and High Impedance with Electrical Weapons.

Introduction: Conducted electrical weapons are primarily designed to stop subjects from endangering themselves or others by deploying 2, or more, probes to conduct current via the body to induce motor-nerve mediated muscle contractions, but probe impedance can vary significantly including open circuits from probes failing to complete or maintain a circuit.

Methods: We tested 10 units of the TASER 7 model with a range of impedances and open circuit conditions. Pulse data (stored in the device's memory) were used to predict the load resistances and detect arcing conditions.

Estimation of Physiological Impedance from Neuromuscular Pulse Data.

Introduction: A Conducted Electrical Weapon (CEW) deploys 2, or more, probes to conduct current via the body to induce motor-nerve mediated muscle contractions, but the inter-probe resistances can vary and this can affect charge delivery. For this reason, newer generation CEWs such as the TASER X3, X2 and X26P models have feed-forward control circuits to keep the delivered charge constant regardless of impedance. Our main goal was to explore the load limits for this "charge metering" system.

Pneumatic Impedance of Spit Socks and N95 Masks: The Applicability to Death Investigation.

Introduction: Restrained subjects often spit on law enforcement and corrections officers and medical responders. Based on the droplet-transmitted risk of COVID-19, such spitting could be considered a potentially life-threatening assault. Officers commonly use "spit socks" over the head and neck of spitting subjects to reduce this risk.

Survival outcomes in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and Drug Administration pooled analysis of patient-level data from three randomised trials.

Background: 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.

Methods: 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.

Arterial aneurysm and dissection with systemic vascular endothelial growth factor inhibitors: A review of cases reported to the FDA Adverse Event Reporting System and published in the literature.

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.

An FDA Review of Drug Development in Nonmetastatic Castration-resistant Prostate Cancer.

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.

Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody.

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.

Applied Force During Prone Restraint: Is Officer Weight a Factor?

Introduction: It has been suggested that law enforcement officer (LEO) weight on the backs of prone subjects may cause asphyxia.

Methods: Law enforcement officers used their agency-trained "local" single- and double-knee techniques, the "Wisconsin" 3-Point Ground Stabilization, and the Human Factor Research Group Inc single-knee tactical handcuffing techniques, and the weight force was measured.

Results: Forty-one LEOs (36 men, 5 women) participated, aged 38.

Electrical Weapon Charge Delivery With Arcing.

Introduction: Human electronic control with the Conducted Electrical Weapon (CEW) has gained widespread acceptance as the preferred law enforcement force option technology due to its dramatic injury and fatal shooting reduction. However, with bulky or baggy clothing, a CEW probe may fail to make direct skin contact and thus arcing is critical to complete the circuit. The goal of the study was to evaluate the ability of modern CEWs to deliver their pulse charges across typical required arcing distances.

Eye injury from electrical weapon probes: Mechanisms and treatment.

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.

Eye injuries from electrical weapon probes: Incidents, prevalence, and legal implications.

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.

New conducted electrical weapons: Thoracic cage shielding effects.

Introduction: The TASER conducted electrical weapon (CEW) delivers electrical pulses that can temporarily incapacitate subjects. For existing CEW models, we have previously presented the distribution of currents in tissues posterior to the sternum and their likelihood of triggering cardiac arrhythmias. New models, the eXperimental Rotating-Field (XRF) waveform CEW (in development) and the X2 CEW (released) have not been investigated.

New conducted electrical weapons: Electrical safety relative to relevant standards.

Introduction: We have previously published about TASER conducted electrical weapons (CEW) compliance with international standards. CEWs deliver electrical pulses that can inhibit a person's neuromuscular control or temporarily incapacitate. An eXperimental Rotating-Field (XRF) waveform CEW and the X2 CEW are new 2-shot electrical weapon models designed to target a precise amount of delivered charge per pulse.