Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

PTSD Coach as an early mobile intervention to improve cancer-related anxiety and psychosocial oncology uptake in patients newly diagnosed with head and neck cancer: pilot randomized controlled trial.

Background: This pilot study aimed to provide supportive evidence for the feasibility of conducting a full-scale intervention trial with patients newly diagnosed with head and neck cancer (HNC). This included assessing the acceptability and potential usefulness of the PTSD Coach mobile app as an early self-management intervention that gives information about anxiety symptoms, offers self-assessment of symptoms with feedback, tools to self-manage anxiety, and connects to support.

Methods: A three-arm randomized controlled trial was conducted.

Assessing Adherence to the PRISMA-DTA Guideline in Diagnostic Test Accuracy Systematic Reviews: A Five-Year Follow-up Analysis.

Background: We evaluated reporting of diagnostic test accuracy (DTA) systematic reviews using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-DTA and PRISMA-DTA for abstracts.

Methods: We searched MEDLINE for recent DTA systematic reviews (September 2023-Mar 2024) to achieve a sample size of 100. Analyses evaluated adherence to PRISMA-DTA (and abstracts), on a per-item basis.

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients.

Genome-wide association studies performed in patients with coronavirus disease 2019 (COVID-19) have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and COVID-19 disease severity. However, the underlying -regulatory genetic factors that contribute to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we used single-cell RNA-sequencing to quantify genetic contributions to -regulatory variation in 361,119 peripheral blood mononuclear cells across 63 COVID-19 patients during acute infection, 39 samples collected in the convalescent phase, and 106 healthy controls.

An adaptive enrichment design using Bayesian model averaging for selection and threshold-identification of predictive variables.

Precision medicine is transforming healthcare by offering tailored treatments that enhance patient outcomes and reduce costs. As our understanding of complex diseases improves, clinical trials increasingly aim to detect subgroups of patients with enhanced treatment effects. Biomarker-driven adaptive enrichment designs, which initially enroll a broad population and later restrict to treatment-sensitive patients, are gaining popularity.

Reproducible protein quantitation of 270 human proteins at increased depth using nanoparticle-based fractionation and multiple reaction monitoring mass spectrometry with stable isotope-labelled internal standards.

Here we show that when using a mix of 274 light synthetic peptide standards (NAT) as surrogates for 270 human plasma proteins, as well as stable isotope-labelled standards (SIS) as normalizers (both from MRM Proteomics Inc.) for targeted quantitative analysis by liquid chromatography multiple reaction monitoring mass spectrometry (LC/MRM-MS), the Seer Proteograph™ platform allowed for the enrichment and absolute quantitation of up to an additional 62 targets (median) compared to two standard proteomic workflows without enrichment, representing an increase of 44%. The nanoparticle-based fractionation workflow resulted in improved reproducibility compared to a traditional proteomic workflow with no fractionation (median 8.

Anticoagulation stewardship in the ambulatory settings of long-term care and rehabilitation - A multi-centric descriptive pilot study.

Background: Anticoagulants have consistently emerged as the leading cause of adverse drug events in both inpatient and outpatient settings. While literature on anticoagulation stewardship programs (ACSP) exists for hospital settings, there is a paucity of data in long-term care and rehabilitation settings.

Objective: Assess the feasibility of a pharmacist led ACSP in the ambulatory healthcare settings of long-term care facilities (LTC) and rehabilitation centers (RC).

Cost-effectiveness analysis of radiofrequency renal denervation for uncontrolled hypertension in Canada.

Aims: Catheter-based radiofrequency renal denervation (RF RDN) is an interventional treatment for uncontrolled hypertension. This analysis explored the therapy's lifetime cost-effectiveness in a Canadian healthcare setting.

Materials And Methods: A decision-analytic Markov model was used to project health events, costs, and quality-adjusted life years over a lifetime horizon.

The Spiral of Attention, Arousal, and Release: A Comparative Phenomenology of Jhāna Meditation and Speaking in Tongues.

Buddhist Jhāna meditation and the Christian practice of speaking in tongues appear wildly distinct. These spiritual techniques differ in their ethical, theological, and historical frames and seem, from the outside, to produce markedly different states of consciousness-one a state of utter calm and the other of high emotional arousal. Yet, our phenomenological interviews with experienced practitioners in the USA found significant points of convergence.

Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial.

Background: The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.

Methods: The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries.

Rationale and design of the PE-TRACT trial: A multicenter randomized trial to evaluate catheter-directed therapy for the treatment of intermediate-risk pulmonary embolism.

Background: The optimal management of patients with intermediate-risk pulmonary embolism (PE), who have right heart dysfunction (determined by a combination of imaging and cardiac biomarkers) but a normal blood pressure, is uncertain. These patients suffer from reduced functional capacity and a lower quality of life over the long-term, despite use of anticoagulant therapy. Catheter-directed therapy (CDT) is a promising treatment for acute PE that rapidly removes thrombus and potentially improves cardiac dysfunction.

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

The Society for Immunotherapy of Cancer Perspective on Tissue-Based Technologies for Immuno-Oncology Biomarker Discovery and Application.

With immuno-oncology becoming the standard of care for a variety of cancers, identifying biomarkers that reliably classify patient response, resistance, or toxicity becomes the next critical barrier towards improving care. Multi-parametric, multi-omics, and computational platforms generating an unprecedented depth of data are poised to usher in the discovery of increasingly robust biomarkers for enhanced patient selection and personalized treatment approaches. Deciding which developing technologies to implement in clinical settings ultimately, applied either alone or in combination, relies on weighing pros and cons, from minimizing patient sampling to maximizing data outputs, and assessing reproducibility and representativeness of findings, while lessening data fragmentation towards harmonization.

A comprehensive experience-based framework of actionable priorities to enhance Canada's health and social care system: discussions with older persons, clinicians, managers, and decision-makers using nominal group technique.

Background: Existing frameworks of older persons' experiences in health and social care systems are usually based on single stakeholder perspectives and focused on limited aspects that are independent from one another. This study aimed to describe such experiences from the perspective of diverse stakeholders and develop a comprehensive experience-based framework for actionable priorities to enhance Canada's health and social care system.

Methods: We adapted a nominal group technique with a qualitative approach.

Formulating recommendations to improve care for persons living with dementia: deliberative dialogues with multiple stakeholders in the province of Quebec, Canada.

Background: Persons living with dementia and their care partners encounter many challenges within the health and social care system, including lack of information, support, counselling, and access to community services, as well as significant staff turnover in home care services. The objective of this study was to work with multiple stakeholders to formulate relevant and feasible recommendations to improve care for persons living with dementia and their care partners in Quebec, Canada.

Methods: We conducted deliberative dialogues in the context of a large mixed methods study on the care of persons living with dementia and care partners.

Building Timely Consensus Among Diverse Stakeholders: An Adapted Nominal Group Technique.

Purpose: Building timely consensus among diverse stakeholders is important in primary health care research. Consensus can be obtained using the nominal group technique which includes 5 steps: (1) introduction and explanation; (2) silent generation of ideas; (3) sharing ideas; (4) discussion; and (5) voting and ranking. The main challenges in using this technique are a lack of representation of different stakeholder opinions and the amount of time taken to reach consensus.

Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool.

Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.

Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.

Design, Setting, And Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population.

RapidBrachyIVBT: A dosimetry software for patient-specific intravascular brachytherapy dose calculations on optical coherence tomography images.

Background: Coronary artery disease is the most common form of cardiovascular disease. It is caused by excess plaque along the arterial wall, blocking blood flow to the heart (stenosis). A percutaneous coronary intervention widens the arterial wall with the inflation of a balloon inside the lesion area and leaves behind a metal stent to prevent re-narrowing of the artery (restenosis).

Association of support group leader experience with Scleroderma Patient-centered Intervention Network Support group Leader EDucation Program outcomes: Secondary analysis of a two-arm parallel partially nested randomized controlled trial.

Introduction/objective: The Scleroderma Patient-centered Intervention Network Support group Leader EDucation Program was found in a randomized controlled trial to substantially improve leader self-efficacy. Whether the program is effective for leaders with different levels of experience, including candidate leaders with no prior experience and leaders with ⩽3 years experience or ⩾4 years experience, is not known. The objective of the present post hoc secondary analysis was to evaluate outcomes by leader experience, age, and education.