ALLG APML5: Bioavailability and safety of oral arsenic trioxide assessed during consolidation therapy for APL.

The prognosis for patients with acute promyelocytic leukemia (APL) has improved dramatically since the introduction of all-trans retinoic acid (ATRA) and intravenous arsenic trioxide (ATO). However, ATO administration requires daily infusions over several months, representing an onerous burden for hospitals and patients. We evaluated the bioavailability of a novel encapsulated oral ATO formulation in APL patients in first complete remission during standard-of-care consolidation.

Perioperative and periprocedural management of GLP-1 receptor-based agonists and SGLT2 inhibitors: narrative review and the STOP-GAP and STOP DKA-2 algorithms.

The GLP-1 receptor-based agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i) are major 21 century breakthroughs in diabetes and obesity medicine but there are important safety considerations regarding the perioperative and periprocedural management of individuals who are treated with these agents. GLP-1RAs have been linked to an increased risk of retained gastric contents and pulmonary aspiration while SGLT2i can be associated with diabetic ketoacidosis. This manuscript provides a narrative review of the available evidence for perioperative and periprocedural risks in people prescribed GLP-1RAs and SGLT2i.

Minor head trauma precipitating acute syndromes in neurogenetic disease.

Most minor head injuries have no immediate neurological sequelae. We present a case where acute neurological symptoms followed a very minor head injury, and an underlying genetic cause was identified. We highlight the role that head injuries, even when innocuous, may have in precipitating and worsening a neurogenetic disorder.

Comprehensive care of ulcerative colitis: new treatment strategies.

Introduction: Ulcerative colitis is a chronic inflammatory condition of the colon driven by aberrant immune activation. Although advanced medical therapies form the cornerstone of ulcerative colitis management, unmet needs include failure to induce and sustain remission in a substantial proportion of patients and in managing acute severe ulcerative colitis. We review new treatment strategies that might improve patient outcomes in the management of moderate-to-severe ulcerative colitis.

Machine-learning based risk prediction of outcomes in patients hospitalised with COVID-19 in Australia: the AUS-COVID score.

Objective: We aimed to develop a highly interpretable and effective, machine-learning based risk prediction algorithm to predict in-hospital mortality, intubation and adverse cardiovascular events in patients hospitalised with COVID-19 in Australia (AUS-COVID Score).

Materials And Methods: This prospective study across 21 hospitals included 1714 consecutive patients aged ≥ 18 in their index hospitalization with COVID-19. The dataset was separated into training (80%) and test sets (20%).

Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age.

Heart failure with preserved ejection fraction (HFpEF) is defined by heart failure (HF) with a left ventricular ejection fraction (LVEF) of at least 50%. HFpEF has a complex and heterogeneous pathophysiology with multiple co-morbidities contributing to its presentation. Establishing the diagnosis of HFpEF can be challenging.

Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials.

Aims: The sodium-glucose cotransporter 2 inhibitor canagliflozin reduces the risk of heart failure (HF) hospitalization or cardiovascular death and chronic kidney disease (CKD) progression among patients with type 2 diabetes at high cardiovascular risk or with CKD. Patients with type 2 diabetes commonly have coexisting HF or CKD that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized.

Methods And Results: In this participant-level pooled analysis of the CREDENCE and CANVAS trials (not including CANVAS-R), 1454/8731 (16.

The Association of Physical Activity With Overweight/Obesity and Type 2 Diabetes in Nepalese Adults: Evidence From a Nationwide Non-Communicable Disease Risk Factor Survey.

Background: The rising prevalence of obesity and type 2 diabetes (T2DM) is a significant public health concern, particularly in low- and middle-income countries. This study aimed to explore the association between physical activity levels, overweight/obesity, and T2DM in a nationwide survey of Nepalese adults.

Methods: This was a secondary analysis of the 2019 non-communicable diseases (NCD) risk factors STEPS survey conducted in Nepal.

The Dynamics of Cognitive Decline towards Alzheimer's Disease Progression: Results from ADSP-PHC's Harmonized Cognitive Composites.

Introduction: Accurately assessing temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presented controversial conclusions likely due to the use of a single cohort and different analytical strategies.

Methods: Harmonized composite cognitive measures in memory, language and executive functions from 13 cohorts in the ADSP-PHC data are used.

Persistent Eosinophilic Inflammation Is Not a Feature of Type 2 CRS Patients Failing Anti-IL-5R Therapy and Requiring Class Switching to Anti-IL-4/13.

Background: Type 2 inflammation dominates eosinophilic chronic rhinosinusitis (eCRS) and adult onset asthma. IL-4, -5, and -13 are prominent disease mediators. Disease control can be achieved with biologic therapies.

Immunotherapy-Resistant Neuropathic Pain and Fatigue Predict Quality-of-Life in Contactin-Associated Protein-Like 2 Antibody Disease.

The long-term clinical outcomes and associated prognostic factors in contactin-associated protein-like 2 (CASPR2)-antibody diseases are unknown. A total of 75 participants with CASPR2 antibodies were longitudinally assessed for disability, quality-of-life, and chronic pain. Although most symptoms improved within 6 months of treatment, neuropathic pain and fatigue were the most immunotherapy refractory, and persisted for up to 6 years.

Effectiveness of a physiotherapist-led triage and treatment service on WAITing time for adults with musculoskeletal pain referred to Australian public hospital physiotherapy clinics: a protocol for the WAIT-less trial.

Introduction: Musculoskeletal pain is the second leading cause of disease burden in Australia, and there is a need to investigate new models of care to cope with the increasing demand for health services. This paper describes the protocol for a randomised controlled trial investigating whether a physiotherapist-led triage and treatment service is non-inferior for improving function at 6 months and superior for reducing treatment waiting times, compared with usual care for patients with musculoskeletal pain referred to public hospital outpatient physiotherapy clinics.

Methods And Analysis: A total of 368 participants (184 per arm) will be recruited from six public hospitals located in metropolitan Sydney, Australia.

Determinants of medication adherence in patients with acute coronary syndrome: a secondary analysis of a randomised clinical trial.

Background: Coronary heart disease (CHD) remains a leading cause of mortality and disability worldwide. Approximately half of the patients who have had a prior hospital admission for CHD will have a recurrent coronary event, with the majority of these occurring within 12 months. Despite well-established evidence-based therapies, medication non-adherence is highly prevalent and reasons for medication non-adherence are poorly understood.

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study.

Background: Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.

Aim: To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.

A Real-World Prospective Multiple Sclerosis Pregnancy Registry in the United States: PREG-MS.

Background And Objectives: Multiple sclerosis (MS) affects more than 1 million people in the United States, including reproductive-age women. There has been a paucity of prospective, pregnancy registries based on MS disease rather than medication exposures. A prospective MS pregnancy registry (PREG-MS) was established in 2017 as a prospective, single-cohort, real-world MS pregnancy registry in New England States of the United States, with goals to evaluate (1) course of MS and disease-modifying therapies (DMT) use during conception attempts and in the peripartum period, (2) pregnancy outcomes in women with MS (WwMS), and (3) longer-term developmental outcomes in offspring of WwMS.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).

Implementation of a data-driven quality improvement program in primary care for patients with coronary heart disease: a mixed methods evaluation of acceptability, satisfaction, barriers and enablers.

Background The study aimed to understand the acceptability, satisfaction, uptake, utility and feasibility of a quality improvement (QI) intervention to improve care for coronary heart disease (CHD) patients in Australian primary care practices and identify barriers and enablers, including the impact of COVID-19. Methods Within the QUality improvement for Effectiveness of care for people Living with heart disease (QUEL) study, 26 Australian primary care practices, supported by five Primary Health Networks (PHN) participated in a 1-year QI intervention (November 2019 - November 2020). Data were collected from practices and PHNs staff via surveys and semi-structured interviews.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Move to improve - Prescribing physical activity and deprescribing paracetamol for low back pain: Protocol for a hybrid type III feasibility study.

Introduction: People experiencing low back pain (LBP) could potentially benefit from multimedia educational resources that integrate self-management strategies and improve awareness of the benefits of staying active and about medications that offer limited benefits, such as paracetamol. Primary care waiting rooms are potential spaces for presenting health promotion resources to improve health literacy through the dissemination of easily accessible health information. This feasibility study aims to explore the feasibility of conducting a large-scale trial to investigate the benefits of multimedia educational resources delivered at outpatient physiotherapy waiting rooms of public hospitals to support patients to participate in physical activity and reduce paracetamol intake for LBP.

ATXN2 polyglutamine intermediate repeats length expansions in Malaysian patients with amyotrophic lateral sclerosis (ALS).

Intermediate CAG repeats from 29 to 33 in the ATXN2 gene contributes to the risk of amyotrophic lateral sclerosis (ALS) in European and Asian populations. In this study, 148 ALS patients of multiethnic descent: Chinese (56.1%), Malay (24.

Comparison of cell-scaffold interactions in a biological and a synthetic wound matrix.

Wound healing is a central physiological process that restores the barrier properties of the skin after injury, comprising close coordination between several cell types (including fibroblasts and macrophages) in the wound bed. The complex mechanisms involved are executed and regulated by an equally complex, reciprocal signalling network involving numerous signalling molecules such as catabolic and anabolic inflammatory mediators (e.g.

Visibility, Physical Work Environment, and Stress in ICU Nurses.

Objective: Relationships among coworker and patient visibility, reactions to physical work environment, and work stress in ICU nurses are explored.

Background: Millions of dollars are invested annually in the building or remodeling of ICUs, yet there is a gap in understanding relationships between the physical layout of nursing units and work stress.

Methods: Using a cross-sectional, correlational, exploratory, predictive design, relationships among variables were studied in a diverse sample of ICU nurses.