Preclinical efficacy of CDK7 inhibitor-based combinations against myeloproliferative neoplasms transformed to AML.

Rising blast-percentage or secondary (s) AML transformation (sAML) in MPNs leads to JAK inhibitor (JAKi) therapy-resistance and poor survival. Here, we demonstrate that the CDK7 inhibitor (CDK7i) SY-5609 treatment depletes phenotypically-characterized post-MPN-sAML stem/progenitor cells. In the cultured post-MPN sAML SET2 and HEL as well as patient-derived (PD) post-MPN-sAML cells, SY-5609 treatment inhibited growth and induced lethality, while sparing normal cells.

Prospective Preference Assessment for the Psilocybin for Enhanced Analgesia in Chronic nEuropathic PAIN (PEACE-PAIN) Trial.

Background: Negative perceptions of psilocybin and challenges of participant enrollment may represent barriers to conducting a randomized controlled trial examining psilocybin for chronic neuropathic pain.

Aim: Prior to trial initiation, we aimed to examine patient attitudes toward the trial via a prospective preference assessment.

Methods: Twenty-six patients with chronic neuropathic pain participated in a prospective preference assessment comprising quantitative (survey) and qualitative (interview) components.

Late Bedtime and Altered Diurnal Axial Length Rhythms of the Eye.

Purpose: Affecting one-third of the population worldwide and increasing, the sight-threatening condition myopia is causing a significant socio-economic burden. To better understand its etiology, recent studies investigated the role of ocular and systemic rhythms, yet results are conflicting. Here we profiled 24-h variations of axial length of the eye and salivary melatonin concentration in young adults with and without myopia and explored the potential impacts of bedtime on these rhythms.

Relationship between Exhaled Aerosol and Carbon Dioxide Emission Across Respiratory Activities.

Respiratory particles produced during vocalized and nonvocalized activities such as breathing, speaking, and singing serve as a major route for respiratory pathogen transmission. This work reports concomitant measurements of exhaled carbon dioxide volume (VCO) and minute ventilation (VE), along with exhaled respiratory particles during breathing, exercising, speaking, and singing. Exhaled CO and VE measured across healthy adult participants follow a similar trend to particle number concentration during the nonvocalized exercise activities (breathing at rest, vigorous exercise, and very vigorous exercise).

The utility of the Montreal cognitive assessment (MoCA) in detecting cognitive impairment in surgical populations - A systematic review and meta-analysis.

Study Objective: To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment (CI) and assess the association of MoCA scores with adverse postoperative outcomes in surgical populations.

Design: Systematic review and meta-analysis.

Setting: Perioperative setting.

Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial.

Objective: People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition.

Design: An assessor-blind, two-armed, parallel-design randomised controlled clinical trial.

Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery.

Background: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach.

Methods: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores.

Psychotherapy for Ketamine's Enhanced Durability in Chronic Neuropathic Pain: Protocol for a Pilot Randomized Controlled Trial.

Background: Chronic pain affects approximately 8 million Canadians (~20%), impacting their physical and mental health while burdening the health care system with costs of upwards of US $60 billion a year. Indeed, patients are often trialed on numerous medications over several years without reductions to their symptoms. Therefore, there is an urgent need to identify new therapies for chronic pain to improve patients' quality of life, increase the availability of treatment options, and reduce the burden on the health care system.

Impact of omitting annual reviews for COPD on patient reported care quality- outcomes from the Asthma+Lung COPD patient passport.

Background: Regular clinical reviews of people with COPD provide an opportunity to optimise management and are recommended in national and international guidelines. However, there are limited data about the relationship between having an annual review and other aspects of care quality, which might influence decision-making by healthcare professionals and commissioners.

Method: Using data from 74 827 people with COPD completing the Asthma+Lung UK COPD Patient Passport, between 2014 and 2022, we conducted adjusted logistic regression (adjusting for year) and compared receipt of key items of care between those reporting that they had had an annual review (65.

Diagnostic accuracy of dual-energy computed tomography in the diagnosis of neurological complications after endovascular treatment of acute ischaemic stroke: a systematic review and meta-analysis.

Objectives: To investigate dual-energy computed tomography's (DECT) diagnostic performance in detecting neurological complications following endovascular therapy (EVT) of acute ischaemic stroke (AIS).

Methods: We performed the literature search using Web of Science, Scopus, PubMed, EBSCO, and Science Direct databases for published related studies. The selected studies estimated the validity of DECT in the detection of neurological complications after EVT for AIS.

Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.

Background: Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam.

Methods: In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.

Functional Outcome of Varus Derotation Osteotomy in Legg-Calve-Perthes Disease: Can It Be Justified in Late-Presenting Disease?

Background: Legg-Calve-Perthes disease (LCPD) in children older than seven years has often been associated with accelerated progress and poor outcome. The results of varus derotation osteotomy (VDRO) of the proximal femur in this cohort are not consistently predictable. This study was aimed at assessing the functional outcome of VDRO for hip containment in children with late-presenting LCPD.

Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis.

Background: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival.

Methods: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions.

Immediate smoking cessation support during lung cancer screening: long-term outcomes from two randomised controlled trials.

Background: Immediate smoking cessation interventions delivered alongside targeted lung health checks (TLHCs) to screen for lung cancer increase self-reported abstinence at 3 months. The impact on longer term, objectively confirmed quit rates remains to be established.

Methods: We followed up participants from two clinical trials in people aged 55-75 years who smoked and took part in a TLHC.

Real-World Insights into Evolocumab Use in Patients with Hyperlipidemia Across Five Countries: Analysis from the ZERBINI Study.

Introduction: This study characterizes patients receiving evolocumab in clinical practice and assesses treatment effectiveness, safety and persistence outcomes across five countries.

Methods: This retrospective and prospective observational study enrolled patients initiated on evolocumab during August 2017 to July 2019 at 49 sites across Canada, Mexico, Colombia, Saudi Arabia and Kuwait. Medical records data were extracted within 6 months prior to (baseline) and every 3 months for 12 months post evolocumab initiation and reported as available.

Conventional anatomical landmark versus preprocedural ultrasound for thoracic epidural analgesia: A systematic review and meta-analysis.

Background: Thoracic epidural analgesia is the gold standard for major thoracic and abdominal surgeries.

Aim: Ultrasound-guided and landmark-based thoracic epidural insertion are compared in this systematic review.

Methods: Randomised controlled trials were sought in six databases for a systematic review and meta-analysis.

Functional inhibition of RECQL5 helicase elicits non-homologous end joining response and sensitivity of breast cancers to PARP inhibitor.

Poly (ADPRibose) Polymerase inhibitor (PARPi) are clinically approved for the treatment of BRCA-mutated hereditary breast and ovarian cancers with homologous recombination (HR) deficiency, based on synthetic lethality concept. However, ∼90% of breast cancers are BRCA-wild type; they repair PARPi mediated damage through HR, leading to intrinsic de novo resistance. Hence, there is an unmet need of exploring novel targets in HR-proficient aggressive breast cancers for PARPi treatment.

Strategies to deliver smoking cessation interventions during targeted lung health screening - a systematic review and meta-analysis.

Introduction: Lung cancer screening presents an important teachable moment to promote smoking cessation, but the most effective strategy to deliver support in this context remains to be established.

Methods: We undertook a systematic review and meta-analysis of smoking cessation interventions delivered during lung health screening, published prior to 20/07/2022 MEDLINE, PsychINFO, CENTRAL, EMBASE, CINAHL and Scopus databases. Two reviewers screened titles, and abstracts, four reviewed each full text using prespecified criteria, extracted relevant data, assessed risk of bias and confidence in findings using the GRADE criteria.