Family, nurse, and physician beliefs on family‐centered rounds: A 21‐site study

BackgroundVariation exists in family-centered rounds (FCR).ObjectiveWe sought to understand patient/family and clinician FCR beliefs/attitudes and practices to support implementation efforts.Designs, settings and participantsPatients/families and clinicians at 21 geographically diverse US community/academic pediatric teaching hospitals participated in a prospective cohort dissemination and implementation study.InterventionWe inquired about rounding beliefs/attitudes, practices, and demographics using a 26-question survey coproduced with family/nurse/attending-physician collaborators, informed by prior research and the Consolidated Framework for Implementation Research.Main outcome and measuresOut of 2578 individuals, 1647 (64%) responded to the survey; of these, 1313 respondents participated in FCR and were included in analyses (616 patients/families, 243 nurses, 285 resident physicians, and 169 attending physicians). Beliefs/attitudes regarding the importance of FCR elements varied by role, with resident physicians rating the importance of several FCR elements lower than others. For example, on adjusted multivariable analysis, attending physicians (odds ratio [OR] 3.0, 95% confidence interval [95% CI] 1.2-7.8) and nurses (OR 3.1, 95% CI 1.3-7.4) were much more likely than resident physicians to report family participation on rounds as very/extremely important. Clinician support for key FCR elements was higher than self-reported practice (e.g., 88% believed family participation was important on rounds; 68% reported it often/always occurred). In practice, key elements of FCR were reported to often/always occur only 23%-70% of the time.ResultSupport for nurse and family participation in FCR is high among clinicians but varies by role. Physicians, particularly resident physicians, endorse several FCR elements as less important than nurses and patients/families. The gap between attitudes and practice and between clinician types suggests that attitudinal, structural, and cultural barriers impede FCR

The Impact of PIK3R1 Mutations and Insulin–PI3K–Glycolytic Pathway Regulation in Prostate Cancer

Abstract Purpose: Oncogenic alterations of the PI3K/AKT pathway occur in &amp;gt;40% of patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance of other PI3K pathway components in prostate cancer is largely unknown. Experimental Design: Patients in this study underwent tumor sequencing using the MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; and structural rearrangements, or were profiled through The Cancer Genome Atlas. The association between PIK3R1 alteration/expression and survival was evaluated using univariable and multivariable Cox proportional-hazards regression models. We used the siRNA-based knockdown of PIK3R1 for functional studies. FDG-PET/CT examinations were performed with a hybrid positron emission tomography (PET)/CT scanner for some prostate cancer patients in the MSK-IMPACT cohort. Results: Analyzing 1,417 human prostate cancers, we found a significant enrichment of PIK3R1 alterations in metastatic cancers compared with primary cancers. PIK3R1 alterations or reduced mRNA expression tended to be associated with worse clinical outcomes in prostate cancer, particularly in primary disease, as well as in breast, gastric, and several other cancers. In prostate cancer cell lines, PIK3R1 knockdown resulted in increased cell proliferation and AKT activity, including insulin-stimulated AKT activity. In cell lines and organoids, PIK3R1 loss/mutation was associated with increased sensitivity to AKT inhibitors. PIK3R1-altered patient prostate tumors had increased uptake of the glucose analogue 18F-fluorodeoxyglucose in PET imaging, suggesting increased glycolysis. Conclusions: Our findings describe a novel genomic feature in metastatic prostate cancer and suggest that PIK3R1 alteration may be a key event for insulin–PI3K–glycolytic pathway regulation in prostate cancer. </jats:sec

A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA) : Rationale, Design, and Baseline Data

Altres ajuts: F. Hoffmann-La Roche Ltd.Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149