Prophylactic radiotherapy for the prevention of procedure-tract metastases after surgical and large-bore pleural procedures in malignant pleural mesothelioma (SMART): a multicentre, open-label, phase 3, randomised controlled trial.

The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Building the Partners HealthCare Biobank at Partners Personalized Medicine: Informed Consent, Return of Research Results, Recruitment Lessons and Operational Considerations

The Partners HealthCare Biobank is a Partners HealthCare enterprise-wide initiative whose goal is to provide a foundation for the next generation of translational research studies of genotype, environment, gene-environment interaction, biomarker and family history associations with disease phenotypes. The Biobank has leveraged in-person and electronic recruitment methods to enroll >30,000 subjects as of October 2015 at two academic medical centers in Partners HealthCare since launching in 2010. Through a close collaboration with the Partners Human Research Committee, the Biobank has developed a comprehensive informed consent process that addresses key patient concerns, including privacy and the return of research results. Lessons learned include the need for careful consideration of ethical issues, attention to the educational content of electronic media, the importance of patient authentication in electronic informed consent, the need for highly secure IT infrastructure and management of communications and the importance of flexible recruitment modalities and processes dependent on the clinical setting for recruitment

Barriers to and Enablers of Implementation of High-Value Interventions by Renal Pharmacists: A Qualitative Study Informed by the Theoretical Domains Framework

ABSTRACTBackground: Previous studies have shown that patients with chronic kidney disease who are followed by a renal clinical pharmacist have improved clinical outcomes. In 2016, a consensus list of quality indicator drug therapy problems (QI-DTPs) was developed by renal clinical pharmacists to help prioritize which renal patients should receive interventions. Before QI-DTP interventions can be implemented in clinical practice, barriers to and enablers of their use need to be identified, to allow development of strategies to overcome the barriers and apply the enablers.Objective: To identify modifiable barriers to and enablers of implementation of renal QI-DTP interventions by renal clinical pharmacists.Methods: In this exploratory qualitative descriptive study, one-on-one, semistructured, audio-recorded telephone interviews were conducted with renal clinical pharmacists to identify the barriers to and enablers of implementation of renal QI-DTP interventions. The interviews consisted of questions developed according to the Theoretical Domains Framework.Results: Interviews were conducted with 13 renal pharmacists from across Canada. The main barriers to implementation of renal QI-DTP interventions that participants identified were knowledge gaps, prioritization, and nephrologist acceptance. The main enablers identified were training, colleague support, and better patient care.Conclusion: Three barriers to and three enablers of implementation of renal QI-DTP interventions were identified. These barriers and enablers can be used to help with pharmacist education and to optimize the care that pharmacists provide to renal patients.RÉSUMÉContexte : Des études précédentes démontrent une amélioration des résultats cliniques de patients souffrant d’une maladie rénale chronique, qui sont suivis par un pharmacien clinicien en néphrologie. En 2016, des pharmaciens cliniciens en néphrologie ont mis au point une liste consensuelle des indicateurs de qualité des problèmes de pharmacothérapie (QI-DTP) pour les aider à prioriser les patients souffrant d’une insuffisance rénale, qui doivent subir une intervention. Avant de mettre en place ces QI-DTP en pratique clinique, on doit déterminer les éléments qui entravent et facilitent leur utilisation pour pouvoir élaborer des stratégies visant à surmonter les obstacles et à appliquer les éléments facilitateurs.Objectif :Déterminer les éléments modifiables qui entravent et facilitent la mise en place des QI-DTP par les pharmaciens cliniciens en néphrologie lors d’interventions rénales.Méthodes : Dans cette étude exploratoire, descriptive et qualitative, des entretiens téléphoniques individuels, semi structurés et enregistrés ont été menés auprès de pharmaciens cliniciens en néphrologie pour determiner les éléments qui entravent et facilitent la mise en place de QI-DTP lors d’interventions rénales. Les entretiens consistaient en des questions préparées selon le Theoretical Domains Framework.Résultats : Les entretiens ont été menés auprès de 13 pharmaciens en néphrologie de partout au Canada. Les principaux éléments entravant la mise en place de QI-DTP lors d’interventions rénales déterminées par les participants étaient : le manque de connaissances, la priorisation et l’acception des néphrologues. Les principaux éléments facilitant la tâche étaient : la formation, le soutien des collègues et de meilleurs soins offerts aux patients.Conclusion : Trois éléments entravant et trois éléments facilitant la mise en place de QI-DTP lors d’interventions rénales ont été déterminés. Ils peuvent être utilisés pour contribuer à la formation du pharmacien et pour optimiser les soins offerts aux patients qui souffrent d’insuffisance rénale

The Information Technology Infrastructure for the Translational Genomics Core and the Partners Biobank at Partners Personalized Medicine

The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT) infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent to the time that genomic data is distributed for research, and enables the management of complex genetic data. Here, we describe the functional components of the research IT infrastructure at Partners Personalized Medicine and how they integrate with existing clinical and research systems, review some of the ways in which this IT infrastructure maintains data integrity and security, and discuss some of the challenges inherent to building and maintaining such infrastructure

The Evolution of a Large Biobank at Mass General Brigham

The Mass General Brigham Biobank (formerly Partners HealthCare Biobank) is a large repository of biospecimens and data linked to extensive electronic health record data and survey data. Its objective is to support and enable translational research focused on genomic, environmental, biomarker and family history associations with disease phenotypes. The Biobank has enrolled more than 135,000 participants, generated genomic data on more than 65,000 of its participants, distributed approximately 153,000 biospecimens, and served close to 450 institutional studies with biospecimens or data. Although the Biobank has been successful, based on some measures of output, this has required substantial institutional investment. In addition, several challenges are ongoing, including: (1) developing a sustainable cost model that doesn’t rely as heavily on institutional funding; (2) integrating Biobank operations into clinical workflows; and (3) building a research resource that is diverse and promotes equity in research. Here, we describe the evolution of the Biobank and highlight key lessons learned that may inform other efforts to build biobanking efforts in health system contexts

Implementation of Electronic Consent at a Biobank: An Opportunity for Precision Medicine Research

The purpose of this study is to characterize the potential benefits and challenges of electronic informed consent (eIC) as a strategy for rapidly expanding the reach of large biobanks while reducing costs and potentially enhancing participant engagement. The Partners HealthCare Biobank (Partners Biobank) implemented eIC tools and processes to complement traditional recruitment strategies in June 2014. Since then, the Partners Biobank has rigorously collected and tracked a variety of metrics relating to this novel recruitment method. From June 2014 through January 2016, the Partners Biobank sent email invitations to 184,387 patients at Massachusetts General Hospital and Brigham and Women’s Hospital. During the same time period, 7078 patients provided their consent via eIC. The rate of consent of emailed patients was 3.5%, and the rate of consent of patients who log into the eIC website at Partners Biobank was 30%. Banking of biospecimens linked to electronic health records has become a critical element of genomic research and a foundation for the NIH’s Precision Medicine Initiative (PMI). eIC is a feasible and potentially game-changing strategy for these large research studies that depend on patient recruitment

Implementation of Electronic Consent at a Biobank: An Opportunity for Precision Medicine Research

The purpose of this study is to characterize the potential benefits and challenges of electronic informed consent (eIC) as a strategy for rapidly expanding the reach of large biobanks while reducing costs and potentially enhancing participant engagement. The Partners HealthCare Biobank (Partners Biobank) implemented eIC tools and processes to complement traditional recruitment strategies in June 2014. Since then, the Partners Biobank has rigorously collected and tracked a variety of metrics relating to this novel recruitment method. From June 2014 through January 2016, the Partners Biobank sent email invitations to 184,387 patients at Massachusetts General Hospital and Brigham and Women’s Hospital. During the same time period, 7078 patients provided their consent via eIC. The rate of consent of emailed patients was 3.5%, and the rate of consent of patients who log into the eIC website at Partners Biobank was 30%. Banking of biospecimens linked to electronic health records has become a critical element of genomic research and a foundation for the NIH’s Precision Medicine Initiative (PMI). eIC is a feasible and potentially game-changing strategy for these large research studies that depend on patient recruitment

Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications

International audienc