Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Why Mental Health Clinicians are Not Engaging in Advance Care Planning with Older People with Schizophrenia and Other Psychotic Illnesses.

Purpose: To explore mental health clinicians' attitudes, experiences, and perceived barriers regarding Advance Care Planning (ACP) with older people (aged 55+) with schizophrenia/other psychotic illnesses.

Methods: Qualitative analysis of focus group interviews with multidisciplinary mental health clinicians from public mental health services in Sydney, Australia. A senior external clinician facilitated online focus groups exploring clinicians' attitudes, experiences, and perceived barriers to ACP using a semi-structured interview guide.

The quality and safety of using generative AI to produce patient-centred discharge instructions.

Patient-centred instructions on discharge can improve adherence and outcomes. Using GPT-3.5 to generate patient-centred discharge instructions, we evaluated responses for safety, accuracy and language simplification.

Ultrastructural overlap between immunotactoid and cryoglobulin glomerulopathy: A case report.

Immunotactoid glomerulopathy (ITG), a condition characterised by highly organised microtubules on electron microscopy, and cryoglobulin glomerulopathy (CG) are rare forms of kidney injury that may be encountered in patients with cryoglobulinaemia. It has been proposed these two entities are part of the same disease process following observed clinical and histological similarities.

Pediatric physiotherapy management of airway clearance therapy and exercise: Data from the Australian Bronchiectasis Registry.

Background: Regular airway clearance techniques (ACTs) and exercise are recommended for children with bronchiectasis, but current clinical practice and their predictors are unknown.

Objective: We aimed to describe current use of ACTs and exercise among Australian children with bronchiectasis and identify associated predictors.

Methods: Physiotherapy-specific data of 397 children (median age = 8 were extracted from the Australian Bronchiectasis Registry.

Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAF-mutant resectable melanoma: the randomized phase 2 NeoTrio trial.

Immune checkpoint inhibitors and BRAF-targeted therapy each improve survival in melanoma. Immune changes early during targeted therapy suggest the mechanisms of each drug class could work synergistically. In the non-comparative, randomized, phase 2 NeoTrio trial, we investigated whether targeted therapy could boost the proportion of patients achieving long-term recurrence-free survival with neoadjuvant immunotherapy in resectable stage III BRAF-mutant melanoma.

The Pathophysiology, Prognosis and Treatment of Hypertension in Females from Pregnancy to Post-menopause: A Review.

Purpose Of Review: We summarise the physiological changes and risk factors for hypertension in females, potential sex-specific management approaches, and long-term prognosis.

Key Findings: Pregnancy and menopause are two key phases of the life cycle where females undergo significant biological and physical changes, making them more prone to developing hypertension. Gestational hypertension occurs from changes in maternal cardiac output, kidney function, metabolism, or placental vasculature, with one in ten experiencing pregnancy complications such as intrauterine growth restriction and delivery complications such as premature birth.

Validation of oscillometric ratio and maximum gradient methods for non-invasive blood pressure measurement with intra-arterial blood pressure measurements as reference.

Most non-invasive blood pressure (BP) measurements are carried out using instruments which implement either the Ratio or the Maximum Gradient oscillometric method, mostly during cuff deflation, but more rarely during cuff inflation. Yet, there is little published literature on the relative advantages and accuracy of these two methods. In this study of 40 lightly sedated individuals aged 64.

Evaluation of the oscillometric method for noninvasive blood pressure measurement during cuff deflation and cuff inflation with reference to intra-arterial blood pressure.

There is little quantitative clinical data available to support blood pressure measurement accuracy during cuff inflation. In this study of 35 male and 5 female lightly anaesthetized subjects aged 64.1 ± 9.

Cost-Consequence Analysis of Deprescribing to Optimize Health Outcomes for Frail Older People: A Within-Trial Analysis.

Objectives: The structured, clinically supervised withdrawal of medicines, known as deprescribing, is one strategy to address inappropriate polypharmacy. This study aimed to evaluate the costs and consequences of deprescribing in frail older people living in residential aged care facilities (RACFs) in Australia.

Design: A within-trial cost-consequence analysis of a deprescribing intervention-Opti-Med.

Treatment with sodium butyrate induces autophagy resulting in therapeutic benefits for spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by the expansion of the trinucleotide repeat region within the ATXN3/MJD gene. Mutation of ATXN3 causes formation of ataxin-3 protein aggregates, neurodegeneration, and motor deficits. Here we investigated the therapeutic potential and mechanistic activity of sodium butyrate (SB), the sodium salt of butyric acid, a metabolite naturally produced by gut microbiota, on cultured SH-SY5Y cells and transgenic zebrafish expressing human ataxin-3 containing 84 glutamine (Q) residues to model SCA3.

Accurate detection of Korotkoff sounds reveals large discrepancy between intra-arterial systolic pressure and simultaneous noninvasive measurement of blood pressure with brachial cuff sphygmomanometry.

Cardiovascular disease is the number 1 cause of death globally, with elevated blood pressure (BP) being the single largest risk factor. Hence, BP is an important physiological parameter used as an indicator of cardiovascular health. Noninvasive cuff-based automated monitoring is now the dominant method for BP measurement and irrespective of whether the oscillometric or the auscultatory method is used, all are calibrated according to the Universal Standard (ISO 81060-2:2019), which requires two trained operators to listen to Korotkoff K1 sounds for SBP and K4/K5 sounds for DBP.

Comparison of cuff inflation and cuff deflation brachial sphygmomanometry with intra-arterial blood pressure as reference.

Conventional sphygmomanometry with cuff deflation is used to calibrate all noninvasive BP (NIBP) instruments and the International Standard makes no mention of calibrating methods specifically for NIBP instruments, which estimate systolic and diastolic pressure during cuff inflation rather than cuff deflation. There is however increasing interest in inflation-based NIBP (iNIBP) instruments on the basis of shorter measurement time, reduction in maximal inflation pressure and improvement in patient comfort and outcomes. However, we have previously demonstrated that SBP estimates based on the occurrence of the first K1 Korotkoff sounds during cuff deflation can underestimate intra-arterial SBP (IA-SBP) by an average of 14 ± 10 mmHg.

The association of dietary antioxidants and the inflammatory potential of the diet with poor physical function and disability in older Australian men: the Concord Health and Ageing in Men Project.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years ( 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy.

Lifestyle changes and quality of life a year after attending Rapid Access Cardiology Clinics: an observational study.

We examined behavioural risk factors and quality of life (QoL) in women and men, younger and older adults 12 months after a Rapid Access Cardiology Clinic (RACC) visit. Routine clinical care data were collected in person from three Sydney hospitals between 2017 and 2018 and followed up by questionnaire at 365 days. 1491 completed the baseline survey, at 1 year, 1092 provided follow-up data on lifestyle changes, and 811 completed the EQ-5D-5L (QoL) survey.

Right Ventricular Dysfunction on Transthoracic Echocardiography and Long-Term Mortality in the Critically Unwell: A Systematic Review and Meta-Analysis.

Objective: Right ventricular dysfunction (RVD) is common in the critically ill. To date studies exploring RVD sequelae have had heterogenous definitions and diagnostic methods, with limited follow-up. Additionally much literature has been pathology specific, limiting applicability to the general critically unwell patient.

OPTIMA: An Open-Label, Noncomparative Pilot Trial of Inhaled Molgramostim in Pulmonary Nontuberculous Mycobacterial Infection.

Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection. This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection ( complex [MAC] and [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability. Thirty-two adult patients with refractory NTM infection (MAC,  = 24; MABS,  = 8) were recruited into two cohorts: those with ( = 16) and without ( = 16) ongoing GBT.

Screening for cancer beyond recommended upper age limits: views and experiences of older people.

Background: Internationally, screening programmes and clinical practice guidelines recommend when older adults should stop cancer screening using upper age limits, but it is unknown how older adults view these recommendations.

Objective: To examine older adults' views and experiences about continuing or stopping cancer screening beyond the recommended upper age limit for breast, cervical, prostate and bowel cancer.

Design: Qualitative, semi-structured interviews.

The SPEC score-A quantifiable CT scoring system for primary ciliary dyskinesia.

Background: Structural lung changes seen on computed tomography (CT) scans in persons with primary ciliary dyskinesia (pwPCD) are currently described using cystic fibrosis (CF) derived scoring systems. Recent work has shown structural changes and frequencies that are unique to PCD, indicating the need for a unique PCD-derived scoring system.

Methods: Chest CT scans from 30 pwPCD, were described for structural changes including bronchiectasis, bronchial wall thickening, mucous plugging, atelectasis, air trapping, and interlobar septal thickening and, additionally, changes previously described as being frequent in pwPCD including extensive tree-in-bud pattern of mucous plugging, bronchoceles or nodules, thickening of interlobar and interlobular septa and whole lobe atelectasis.

IBD barriers across the continents: a continent-specific analysis - Australasia.

Australasia, encompassing Australia, New Zealand, and Papua New Guinea, has some of the highest prevalence's of inflammatory bowel disease (IBD) in the world. The way IBD medicine is practiced varies between and within these countries. There are numerous shared issues of IBD care between Australia and New Zealand, whereas Papua New Guinea has its' own unique set of circumstances.