Comparative efficacy and safety of talazoparib plus enzalutamide and other first-line treatments for metastatic castration-resistant prostate cancer.

Background: Talazoparib plus enzalutamide (TALA + ENZA) has demonstrated antitumor activity in the phase 3 clinical trial (TALAPRO-2; NCT03395197) as first-line (1L) therapy in men with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC). Although many active interventions are available, randomized controlled trials (RCTs) involving talazoparib have only been conducted to assess its efficacy and safety compared to enzalutamide. To estimate comparisons between all relevant interventions, indirect comparisons are needed.

Predicting Treatment Effects from Surrogate Endpoints in Historical Trials in First-Line Metastatic Castration-Resistant Prostate Cancer.

Surrogate endpoints are becoming increasingly important in health technology assessment, where decisions are based on complex cost-effectiveness models (CEMs) that require numerous input parameters. Daniels and Hughes Surrogate Model was used to predict missing effect estimates in randomized controlled trials (RCTs) evaluating first-line treatments in metastatic castration-resistant prostate cancer (mCRPC) patients. Network meta-analyses (NMAs) were conducted to assess the comparative efficacy of these treatments.

Host IPR channels are dispensable for rotavirus Ca signaling but critical for intercellular Ca waves that prime uninfected cells for rapid virus spread.

Many viruses exploit host Ca signaling to facilitate their replication; however, little is known about how Ca signals from different host and viral channels contribute to the overall dysregulation of Ca signaling or promote virus replication. Using cells lacking IPR, a host ER Ca channel, we delineated intracellular Ca signals within virus-infected cells and intercellular Ca waves (ICWs), which increased Ca signaling in neighboring, uninfected cells. In infected cells, IPR was dispensable for rotavirus-induced Ca signaling and replication, suggesting the rotavirus NSP4 viroporin supplies these signals.

The Inositol Trisphosphate Receptor (IP R) is Dispensable for Rotavirus-induced Ca Signaling and Replication but Critical for Paracrine Ca Signals that Prime Uninfected Cells for Rapid Virus Spread.

Unlabelled: Rotavirus is a leading cause of viral gastroenteritis. A hallmark of rotavirus infection is an increase in cytosolic Ca caused by the nonstructural protein 4 (NSP4). NSP4 is a viral ion channel that releases Ca from the endoplasmic reticulum (ER) and the increase in Ca signaling is critical for rotavirus replication.

Exercise therapy for chronic low back pain.

Background: Low back pain has been the leading cause of disability globally for at least the past three decades and results in enormous direct healthcare and lost productivity costs.

Objectives: The primary objective of this systematic review is to assess the impact of exercise treatment on pain and functional limitations in adults with chronic non-specific low back pain compared to no treatment, usual care, placebo and other conservative treatments.

Search Methods: We searched CENTRAL (which includes the Cochrane Back and Neck trials register), MEDLINE, Embase, CINAHL, PsycINFO, PEDro, SPORTDiscus, and trials registries (ClinicalTrials.

Some types of exercise are more effective than others in people with chronic low back pain: a network meta-analysis.

Question: What are the effects of specific types of exercise treatments on pain intensity and functional limitation outcomes for adults with chronic low back pain?

Design: Systematic review with network meta-analysis of randomised controlled trials.

Participants: Adults with non-specific low back pain for ≥ 12 weeks.

Intervention: Exercise treatments prescribed or planned by a health professional that involved conducting specific activities, postures and/or movements with a goal to improve low back pain outcomes.

Prolonged opioid use among opioid-naive individuals after prescription for nonspecific low back pain in the emergency department.

Low back pain is a leading cause of disability globally. It is a common reason for presentation to the emergency department where opioids are commonly prescribed. This is a retrospective cohort study of opioid-naive adults with low back pain presenting to 1 of 4 emergency departments in Nova Scotia.