Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs

Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold

Factors associated with suicide attempts among Australian transgender adults

BACKGROUND: Transgender, including gender diverse and non-binary people, henceforth referred to collectively as trans people, are a highly marginalised population with alarming rates of suicidal ideation, attempted suicide and self-harm. We aimed to understand the risk and protective factors of a lifetime history of attempted suicide in a community sample of Australian trans adults to guide better mental health support and suicide prevention strategies. METHODS: Using a non-probability snowball sampling approach, a total of 928 trans adults completed a cross-sectional online survey between September 2017 and January 2018. The survey assessed demographic data, mental health morbidity, a lifetime history of intentional self-harm and attempted suicide, experiences of discrimination, experiences of assault, access to gender affirming healthcare and access to trans peer support groups. Logistic regression was used to examine the risk or protective effect of participant characteristics on the odds of suicide. RESULTS: Of 928 participants, 85% self-reported a lifetime diagnosis of depression, 63% reported previous self-harm, and 43% had attempted suicide. Higher odds of reporting a lifetime history of suicide attempts were found in people who were; unemployed (adjusted odds ratio (aOR) 1.55 (1.05, 2.29), p = 0.03), had a diagnosis of depression (aOR 3.70 (2.51, 5.45), p < 0.001), desired gender affirming surgery in the future (aOR 1.73 (1.14, 2.61), p = 0.01), had experienced physical assault (aOR 2.01 (1.37, 2.95), p < 0.001) or experienced institutional discrimination related to their trans status (aOR 1.59 (1.14, 2.23), p = 0.007). CONCLUSION: Suicidality is associated with barriers to gender affirming care, gender based victimisation and institutionalised cissexism. Interventions to increase social inclusion, reduce transphobia and enable timely access to gender affirming care, particularly surgical interventions, are potential areas of intervention

The impact of the first three months of the COVID-19 pandemic on the Australian trans community

Published online: 11 Mar 2021. OnlinePublBackground: Trans and gender diverse individuals (people who identify with a gender different to what was presumed for them at birth) are one of the most medically and socially marginalized groups in our community. The COVID-19 pandemic may compound preexisting depression and thoughts of self-harm or suicide. Aim: We aimed to explore the impact of the COVID-19 pandemic on the Australian trans community. Methods: An online cross-sectional survey was conducted between 1st May 2020 and 30th June 2020, amidst strict Australia-wide social restrictions. Australian trans people aged ≥16 years were eligible to participate. Survey questions explored the impact of the COVID-19 pandemic on living situation, employment, financial situation, and healthcare. Logistic regression to assess negative impacts due to COVID-19 on depression and thoughts of self-harm or suicide (measured by Patient Health Questionnaire-9 (PHQ-9) are presented as odds ratios (95% confidence interval)). Results: Of 1019 participants, 49.6% reported experiencing financial strain, 22% had reduced working hours, and 22.4% were unemployed (three times the national rate). Concerningly, 61.1% experienced clinically significant symptoms of depression (Patient Health Questionnaire-9 score ≥10), considerably higher than pre-COVID rates for the trans community and over twice the national rate. Moreover, 49% reported thoughts of self-harm or suicide (over three times the national rate) which was more likely if a person experienced cancelation or postponement of gender-affirming surgery (OR 1.56 (1.04, 2.35)), financial strain (OR 1.80 (1.36, 2.38)), or felt unsafe or afraid in their household (OR 1.96 (1.23, 3.08)). Discussion: Given rates of clinically significant depression and thoughts of self-harm or suicide are far higher in trans people than the general population, specific strategies to improve mental health in the trans community during the COVID-19 pandemic must be made a priority for policymakers, researchers, and health service providers to prevent suicide.Sav Zwickl, Lachlan M. Angus, Alex Wong Fang, Ariel Ginger, Kalen Eshin, Teddy Cook ... et al

83 Utilization of Ultrasound in Resuscitation Rooms in an Urban Level 1 Trauma Center

Study Objectives: The resuscitation rooms of emergency departments (EDs) are resource rich rooms that are fast paced and costly to maintain and operate. Often times, point-of-care ultrasound (POCUS) is used in ED resuscitation rooms as one of the resources for immediate diagnosis, to assist medical decision making, and aid the course of treatment. Unfortunately, failure of POCUS documentation along with the lack of patient charges may result in the possible loss of hospital revenue. The primary objective of the study is to assess the effects of educating residents on the importance of documenting POCUS procedures in resuscitation rooms into the patient chart and saving the image(s) to the US machine. Secondary objectives include assessing the types of patients utilizing the POCUS in resuscitation rooms, evaluating the documentation of procedures of POCUS, and to identify potential improvement in billing and revenue capture. Methods: This is an observational cohort study. 467 patients were included prior to resident education on US documentation and 498 patients were included post education. Documentation of ultrasound use and whether images were saved to QPATHE were summarized by counts, percentages, and 95% confidence intervals. Chi-square tests were used for the comparison between pre- and post-resident education and the t-test was used for the continuous variable. Significance was inferred at