Citations

Context.— The US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for SARS-CoV-2 assays encompassed both in vitro diagnostic and laboratory-developed tests. Related testing data and documents from EUAs were published on the FDA website as PDF files, constituting a rich data resource. Objective.— To highlight the value of structured descriptive and validation data and provide recommendations on improving the quality, accessibility, and shareability of the FDA’s digital resources. Design.— SARS-CoV-2 diagnostics EUAs and related files were acquired from the FDA, and data were extracted through an iterative manual or automated process with quality assurance in accordance with a set of data entry definitions to generate a data product (ie, data analysis and presentation of data into tables, graphs, and reports, optionally including different data sets) that could be disseminated. Results.— Four challenges limited the usability of FDA EUA data, including (1) distinguishing EUA tests owing to similar names or inconsistent naming conventions; (2) document location and tracking owing to inconsistent EUA document identifiers, resource locators, and versioning; (3) data location and retrieval owing to heterogeneous structure and data formatting within EUA documentation; and (4) maintenance of existing data owing to lack of clear and traceable communication around EUA amendments. Conclusions.— Converging efforts from disparate groups to extract and synthesize FDA test data reveal an unaddressed need for better organization and communication. Existing FDA data reporting systems must be improved and adapted for the demands of the connected data science era.

Abstract Background: As with most Sub-Saharan African countries, Nigeria has a rising incidence of cancer, with disproportionate mortality rates. The financial burden of cancer care often results in catastrophic healthcare spending, leading to treatment refusal, disruption, and discontinuation. This is particularly significant in Nigeria, where nearly all patients are uninsured, and out-of-pocket costs often exceed households’ ability to pay. Financial Navigation Programs (FNPs) have been shown to mitigate treatment-related financial toxicity in cancer care and reduce treatment abandonment, but there is a paucity of high-quality data on this intervention in resource-constrained settings. Here, we present a randomized controlled trial to evaluate the impact of a novel FNP in Nigeria. Methods: We designed the COST-FIN trial, a multi-site pragmatic single-blinded randomized controlled trial of newly diagnosed (<6 weeks from diagnosis) adults (≥18 years) with breast, colorectal, or prostate cancer at two tertiary cancer centers in Nigeria. Participants (n=200) will be randomized (1:1) to either the intervention (FNP) or the control arm and followed for 12 months. Data on key individual, treatment, and financial parameters will be collected via structured interviews and chart abstraction at baseline, 3, 6, and 12-month follow-up. In addition, participants randomized to the FNP will receive a tailored financial literacy assessment, financial planning support, and enhanced access to resources by trained financial navigators. Primary and secondary outcomes are Financial Catastrophe (FC) and Financial Distress (FD), respectively. Exploratory outcomes will include cost-related non-adherence and cost-effectiveness of the program. An interim analysis will be conducted when 50% of the estimated accruals reach 6 months of follow-up, with crossover if compelling evidence of benefit is demonstrated at that time point. All participants will be followed for 12 months from recruitment. Discussion: This first-of-its-kind study will provide evidence on the role of FNP in potentially eliminating financial barriers to cancer care in Nigeria. Given the country’s renewed interest in cancer control through the passage of the National Cancer Control Plan, findings from this study have the potential to influence policy reform and set the stage for further studies to evaluate the scalability and implementation of similar interventions in resource-limited settings. Trial registration : ClinicalTrials.gov NCT06630962. Oct 8, 2024 (https://clinicaltrials.gov/study/NCT06630962)

Metabolic dysfunction-associated steatohepatitis (MASH) is a global health care burden. Appropriate large animal models mimicking the main MASH characteristics of steatosis, inflammation, and hepatocyte damage alongside progression of fibrosis are imperative for robust preclinical studies, especially in the field of hepatobiliary surgery. The present study aimed to characterize a novel model of steatohepatitis in fumarylacetoacetate hydroxylase-deficient ( FAH -/- ) pigs. FAH -/- pigs were generated using a CRISPR/Cas9 system. The animals received a choline-deficient, L-amino acid-defined high-fat diet and subtherapeutic doses of nitisinone and were followed for 3 months. Liver biopsies were obtained at baseline and every month during treatment. Steatosis, inflammation, and fibrosis were assessed by conventional histological scoring systems and by an artificial intelligence (AI) model. Serum liver parameters were analyzed every 2 weeks. Steatosis increased significantly throughout the study, with severe steatosis observed as early as 2 months into treatment. The inflammation score was increased in all animals after 3 months of treatment, whereas the AI-based CD45+ cell count showed region-specific trends in the portal and lobular areas. Collagen content and the corresponding fibrosis stage showed an increase over the 3-month period; however, the difference was not significant. Serum liver parameters did not show any relevant elevations during the study. In summary, we successfully developed and characterized a novel model of steatohepatitis in the FAH -/- pig within 3 months. Further studies with prolonged observation time and/or cycling of nitisinone administration are needed to evaluate whether progressive fibrosis and cirrhosis could be achieved with this model.

Objective: The Society of Critical Care Medicine PICU Liberation ABCDEF (A–F) Campaign Collaborative aimed to implement best practices for analgesia (A), breathing (B), comfort/consciousness (C), delirium (D), early mobilization (E), and family engagement and empowerment (F). Our post hoc study of Mayo Clinic data sought to compare the pre-implementation rounding process, which used a nursing script organized by organ systems, with a novel, liberation-focused rounding process emphasizing A–F bundle elements. Design: Secondary analysis of pre- vs. post-implementation surveys collected by independent observers during rounds. Setting: Medical/surgical PICU in a quaternary-care, academic medical center during April to July 2017. Subjects: The observed participants included PICU physicians, nurses, respiratory therapists, pharmacists, and dietitians. Interventions: None. Measurements and Main Results: Survey responses from 145 team members pre-implementation and 67 post-implementation showed improved team satisfaction, communication, and understanding of daily plans (all p < 0.05). Respondents reported an increased frequency of discussions on bundle components A–E (all p < 0.01). Observations of 41 pre-implementation and 46 post-implementation rounds showed an increase in the frequency of discussion of all components of the bundle (all p < 0.01). However, this finding was not at the expense of increased duration of individual rounds since we failed to find a difference in pre- vs. post-implementation duration per patient (480 vs. 544 s per patient, p = 0.20). Conclusions: In 2017, around the time of introducing the nurse-led PICU Liberation rounding process to our practice, we found that after implementation, there was an associated increase in discussions about bundle elements and improved communications and satisfaction in team members.

Abstract Background The number of cancer survivors aged older than 65 years is rising rapidly. Current evidence‐based exercise guidelines lack specific guidance for older cancer survivors as a result of insufficient evidence. An expert panel was convened to develop consensus‐based recommendations for exercise in older cancer survivors. Methods The development of recommendations was guided by the Grading of Recommendations Assessment, Development, and Evaluation Evidence‐to‐Decision framework for good practice statements. The panel drew from the available literature, a Delphi survey of exercise and health professionals, other exercise guidelines, clinical and research expertise, and interest‐holder input provided by a community advisory board of older cancer survivors and caregivers ( n = 11). Recommendations had to be deemed accessible (i.e., no added barriers) to older cancer survivors and feasible to implement. The panel voted on the strength of the recommendation for or against each statement, with consensus set at 85% agreement. Results Consensus was reached on 11 recommendations covering the following areas: medical evaluation/clearance for exercise, pre‐exercise assessment, exercise prescription, exercise tolerance and safety, exercise delivery, and behavioral support. The recommendations aimed to promote engagement in and uptake of appropriately prescribed exercise programming by older cancer survivors, while keeping barriers and risks as low as possible. Conclusions Older cancer survivors can benefit from appropriately prescribed exercise, which should be an essential component of their cancer care. Exercise and health professionals need to consider the unique needs of older cancer survivors to ensure that exercise is safe and effective for this population, while also reducing barriers to reach as many people as possible.

ABSTARCT BACKGROUND: IRRAflow is a novel active cerebrospinal fluid (CSF) exchange system for the treatment of hemorrhagic strokes and intracranial infections. It is a closed system that irrigates various medications dissolved in irrigation solutions at a speed of up to 180 mL/h, expediting resolution. Disrupting this closed system to withdraw CSF samples or infuse medications is necessary in certain circumstances. We report our novel approach for maintaining the sterility of the closed IRRAflow system using a needleless extension and assess the compatibility and safety of this technology throughout treatment. METHODS: We used a needleless extension to withdraw CSF samples and deliver medications to 5 patients treated with the IRRAflow system. We used 1 stopcock with a 3-way valve, 2 neutral needleless connectors, and 2 antiseptic caps. The stopcock was connected between the irrigation and drainage ports of the catheter. The needleless connectors were mounted at the 12 o’clock position of the attached stopcock and the irrigation port with antiseptic caps covering the distal ends. To initiate fluid exchange, the 2 needleless connectors were separated. The extra stopcock valve was connected between the drainage arm, the cassette, and the irrigation arm. The needleless connectors remained mounted at the 12 o’clock position of the stopcock and irrigation port throughout treatment. RESULTS: The needleless connectors mounted on the 12 o’clock position of the stopcock and irrigation port on the drainage and irrigation arms, respectively, provided efficient management of fluid exchange, CSF fluid sampling, and medication delivery. Our needleless extension was compatible with the IRRAflow device and prevented secondary infections despite repeated CSF sampling and medication delivery. CONCLUSION: The needleless extension facilitated a simple and safe interaction with the closed IRRAflow system without compromising the sterile environment during CSF sampling and medication delivery.

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P&lt; .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with Type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischaemic stroke and examined trends and disparities. Methods and results Using nationwide Czech registry data (2015–24), we identified patients with incident nonfatal MI or ischaemic stroke and confirmed T2D. GLP-1RA users—initiating therapy within 12 months post-event—were propensity score matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality. GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126 845 MI survivors, 28 206 had T2D; the matched cohort comprised 2271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR 0.7; 95% CI, 0.52–0.93), all-cause (HR 0.61; 95% CI, 0.47–0.80), and cardiovascular death (HR 0.54; 95% CI, 0.36–0.80). Among 177 115 stroke survivors, 73 750 had T2D; the matched cohort comprised 2235 patients (385 GLP-1RA; median follow-up 27 months). GLP-1RA use was associated with lower risk of MACE (HR 0.71; 95% CI, 0.54–0.94), all-cause (HR 0.59; 95% CI, 0.46–0.76), and cardiovascular death (HR 0.55; 95% CI, 0.37–0.81). Conclusion GLP-1RA therapy after MI or stroke in T2D was associated with substantially lower risks of MACE, cardiovascular, and all-cause death in real-world practice. Utilization remained low, particularly among women and older adults, underscoring the need for broader and more equitable implementation in secondary prevention.