Have interventions aimed at assisting general practitioners in facilitating earlier diagnosis of type 1 diabetes in children been successful in preventing acute complications? A systematic review.

Background: Diabetic ketoacidosis (DKA) is a life-threatening emergency that can result from delayed diagnosis of type 1 diabetes mellitus (T1DM). Three-quarters of Australian children with a new diagnosis of T1DM visit their general practitioner (GP) the week prior to developing DKA, with similar trends observed internationally.

Objective: To summarise interventions in general practice to reduce diagnostic delay in paediatric T1DM and to evaluate their effectiveness.

Multipad agarose plate: a rapid and high-throughput approach for antibiotic susceptibility testing.

We describe a phenotypic antibiotic susceptibility testing (AST) method that can provide an eightfold speed-up in turnaround time compared with the current clinical standard by leveraging advances in microscopy and single-cell imaging. A newly developed growth plate containing 96 agarose pads, termed the multipad agarose plate (MAP), can be assembled at low cost. Pads can be prepared with dilution series of antibiotics.

Bioinformatic investigation of discordant sequence data for SARS-CoV-2: insights for robust genomic analysis during pandemic surveillance.

The COVID-19 pandemic has necessitated the rapid development and implementation of whole-genome sequencing (WGS) and bioinformatic methods for managing the pandemic. However, variability in methods and capabilities between laboratories has posed challenges in ensuring data accuracy. A national working group comprising 18 laboratory scientists and bioinformaticians from Australia and New Zealand was formed to improve data concordance across public health laboratories (PHLs).

Activating pharmacists to reduce the frequency of medication-related problems (ACTMed): a stepped wedge cluster randomised trial.

Background: Medicines are the most frequent health care intervention type; their safe use provides significant benefits, but inappropriate use can cause harm. Systemic primary care approaches can manage serious medication-related problems in a timely manner.

Objectives: ACTMed (ACTivating primary care for MEDicine safety) uses information technology and financial incentives to encourage pharmacists to work more closely with general practitioners to reduce the risk of harm, improve patients' experience of care, streamline workflows, and increase the efficiency of medical care.

Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators.

Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis.

Association between hypomania and self-harm behaviors in Chinese children and adolescents with depressive symptoms.

Bipolar disorder (BD) is associated with a higher risk of self-harm (SH) when compared with depression. Therefore, it is reasonable to suspect that the state of mania or hypomania may independently contribute to increased SH risk. However, for hypomania, its association with SH remains less known.

Thirty-year clinical outcomes after haematopoietic stem cell transplantation in neuronopathic Gaucher disease.

Background: Neuronopathic Gaucher Disease (nGD) describes the condition of a subgroup of patients with the Lysosomal Storage Disorder (LSD), Gaucher disease with involvement of the central nervous system (CNS) which results from inherited deficiency of β-glucosylceramidase. Although systemic manifestations of disease are now corrected by augmentation with macrophage-targeted therapeutic enzyme (enzyme replacement therapy, ERT), neurological disease progresses unpredictably as a result of failure of therapeutic enzyme to cross the blood-brain barrier (BBB). Without therapy, the systemic and neurological effects of the disease progress and shorten life: investigators, principally in Sweden and the UK, pioneered bone marrow transplantation (BMT; Haematopoietic Stem Cell Transplantation HSCT) to supply healthy marrow-derived macrophages and other cells, to correct the peripheral disease.

Systematic Review and Meta-Analysis to Estimate the Treatment Effect and Inform a Noninferiority Margin for a Phase 3 Noninferiority Trial in Uncomplicated Urogenital Gonorrhea.

Background: Active-controlled noninferiority studies are used to investigate novel agents for uncomplicated urogenital gonorrhea (uUGC) as placebo-controlled trials are unethical. A systematic literature review and meta-analysis were conducted to estimate the ceftriaxone and proxy-for-placebo microbiological treatment effect and determine an appropriate noninferiority margin for phase 3 trials.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.

Unmet Dental Needs Among Mid-to-Older Deaf and Hard of Hearing Women in the U.S.

Introduction: Despite the significant number of deaf and hard of hearing (DHH) people living in the U.S., oral health research on DHH people who use American Sign Language (ASL) is virtually nonexistent.

Lab-in-a-van: Rapid SARS-CoV-2 testing response with a mobile laboratory.

Background: High testing rates and rapid contact tracing have been key interventions to control COVID-19 in Victoria, Australia. A mobile laboratory (LabVan), for rapid SARS-CoV-2 diagnostics, was deployed at sites deemed critical by the Victorian State Department of Health as part of the response. We describe the process of design, implementation, and performance benchmarked against a central reference laboratory.

Resilience mediates the association between impulsivity and self-harm in Chinese adolescents.

Objective: Existing literature is supportive for the positive connection between impulsivity and self-harm (SH), nevertheless, less is known regarding to the role of resilience in this association. This research primarily explored potential mediation of resilience in the association between impulsivity and SH in a large sample of Chinese adolescents.

Method: A population-based cross-sectional survey of 4552 adolescents was conducted in southwest China.

In-depth phenotyping for clinical stratification of Gaucher disease.

Background: The Gaucher Investigative Therapy Evaluation is a national clinical cohort of 250 patients aged 5-87 years with Gaucher disease in the United Kingdom-an ultra-rare genetic disorder. To inform clinical decision-making and improve pathophysiological understanding, we characterized the course of Gaucher disease and explored the influence of costly innovative medication and other interventions. Retrospective and prospective clinical, laboratory and radiological information including molecular analysis of the GBA1 gene and comprising > 2500 variables were collected systematically into a relational database with banking of collated biological samples in a central bioresource.

Experiences of and attitudes to lifestyle modification for the management of multiple sclerosis: A qualitative analysis of free-text survey data.

Background: Growing evidence suggests a role of lifestyle modification in improved health outcomes for people with multiple sclerosis (pwMS); however, perspectives of pwMS who engage in lifestyle modification are lacking.

Objective: We explored perspectives of pwMS regarding the modification of lifestyle-related risk factors in multiple sclerosis (MS) for disease management to understand attitudes to and experiences of lifestyle modification as part of self-management from a patient perspective.

Design: Participants were ≥18 years and English speaking who responded to a free-text open-ended question in the Health Outcomes and Lifestyle In a Sample of pwMS (HOLISM), an international online survey.

Throwing a spotlight on under-recognized manifestations of Gaucher disease: Pulmonary involvement, lymphadenopathy and Gaucheroma.

Background: Gaucher disease (GD) is a rare lysosomal storage disorder classically subdivided into type 1 (non-neuronopathic) GD, and types 2 and 3 (neuronopathic) GD. It is typically characterized by clinical manifestations including anemia, thrombocytopenia, hepatosplenomegaly, bone lesions, and (in more severe forms) neurological impairment. However, less-commonly reported and often under-recognized manifestations exist, which potentially have a significant impact on patient outcomes.

Wearable Technologies for Children with Chronic Illnesses: An Exploratory Approach.

Objective: To determine the utility of wearable technologies in physical activity assessment in three paediatric diseases, namely, Niemann-Pick C (NP-C), Juvenile Idiopathic Arthritis (JIA) and Duchenne Muscular Dystrophy (DMD).

Design: Exploratory study SETTING AND PATIENTS: Thirty children were recruited across three UK hospitals (Royal Manchester's Children Hospital, Great Ormond Street Children's Hospital, and the Great North Children's Hospital). Ten were diagnosed with NP-C, eight with DMD and twelve with JIA.

Impulsivity mediates the association between parenting styles and self-harm in Chinese adolescents.

Background: Parenting styles are significantly associated with self-harm (SH) in adolescents. Nevertheless, little is known about the mechanism underlying this association. This study primarily aimed to evaluate the potential mediating role of impulsivity in the association between parenting styles and SH in Chinese adolescents.

Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease.

Background: Neurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with enzyme replacement therapy, however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials.

Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK.

Purpose: To use physiologically-based pharmacokinetic (PBPK) modelling to explore the food effect of different DNX hydrobromide (HBr) hemihydrate salt tablet formulations using biorelevant dissolution.

Methods: Compendial dissolution using a paddle method and TIM-1 biorelevant dissolution were performed and incorporated into a previously reported PBPK model. A two-part clinical study evaluated tablet formulations in the fasted/fed (high fat) state (Part A), and the impact of food (fasted/normal/high fat) and Proton Pump Inhibitor (PPI) co-administration for a selected formulation; as well as a formulation containing DNX HBr in the monohydrate state (Part B).

A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2.

Many human cancers over-express B cell lymphoma 2 (Bcl-2) or X-linked inhibitor of apoptosis (IAP) proteins to evade cell death. The pro-apoptotic ARTS (Sept4_i2) protein binds directly to both Bcl-2 and XIAP and promotes apoptosis by stimulating their degradation via the ubiquitin-proteasome system (UPS). Here we describe a small molecule, A4, that mimics the function of ARTS.

CXCR2 antagonist for patients with chronic obstructive pulmonary disease with chronic mucus hypersecretion: a phase 2b trial.

Background: Oral CXC chemokine receptor 2 (CXCR2) antagonists have been shown to inhibit neutrophil migration and activation in the lung in preclinical and human models of neutrophilic airway inflammation. A previous study with danirixin, a reversible CXCR2 antagonist, demonstrated a trend for improved respiratory symptoms and health status in patients with COPD.

Methods: This 26-week, randomised, double-blind, placebo-controlled phase IIb study enrolled symptomatic patients with mild-to-moderate COPD at risk for exacerbations.