Safety, Pharmacokinetics, and Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-Associated Hepatitis.

INTRODUCTION: This study is to evaluate the safety and pharmacokinetics (PK) of larsucosterol (DUR-928 or 25HC3S) in subjects with alcohol-associated hepatitis (AH), a devastating acute illness without US Food and Drug Administration-approved therapies. METHODS: This phase 2a, multicenter, open-label, dose escalation study evaluated the safety, PK, and efficacy signals of larsucosterol in 19 clinically diagnosed subjects with AH. Based on the model for end-stage liver disease (MELD) score, 7 subjects were considered to have moderate AH and 12 to have severe AH. All subjects received 1 or 2 intravenous infusions (72 hours apart) of larsucosterol at a dose of 30, 90, or 150 mg and were followed up for 28 days. Efficacy signals from a subgroup of subjects with severe AH were compared with those from 2 matched arms of those with severe AH treated with standard of care (SOC), including corticosteroids, from a contemporaneous study. RESULTS: All 19 larsucosterol-treated subjects survived the 28-day study. Fourteen (74%) of all subjects including 8 (67%) of the subjects with severe AH were discharged ≤72 hours after receiving a single infusion. There were no drug-related serious adverse events nor early terminations due to the treatment. PK profiles were not affected by disease severity. Biochemical parameters improved in most subjects. Serum bilirubin levels declined notably from baseline to day 7 and day 28, and MELD scores were reduced at day 28. The efficacy signals compared favorably with those from 2 matched groups treated with SOC. Lille scores at day 7 were <0.45 in 16 of the 18 (89%) subjects with day 7 samples. Lille scores from 8 subjects with severe AH who received 30 or 90 mg larsucosterol (doses used in phase 2b trial) were statistically significantly lower ( P < 0.01) than those from subjects with severe AH treated with SOC from the contemporaneous study. DISCUSSION: Larsucosterol was well tolerated at all 3 doses in subjects with AH without safety concerns. Data from this pilot study showed promising efficacy signals in subjects with AH. Larsucosterol is being evaluated in a phase 2b multicenter, randomized, double-blinded, placebo-controlled (AHFIRM) trial.

Brigham Eyebrow Tool for Alopecia: A Reliable Assessment of Eyebrow Alopecia Areata.

There are no tools to evaluate eyebrow involvement in patients with alopecia areata. We developed and assessed the reliability of the Brigham Eyebrow Tool for Alopecia (BETA) as a quantitative evaluation of eyebrow alopecia areata. BETA uses facial landmarks of eyebrow anatomy and is calculated using surface area and density. A total of 50 eyebrow images with varying levels of hair loss were distributed to six board-certified dermatologists at three academic medical centers with standardized instructions and examples. Interrater and intrarater reliability were calculated using intraclass correlation coefficients (ICCs). BETA demonstrated high interrater (ICC = 0.88, confidence interval = 0.83-0.92 right eyebrow scores and ICC = 0.90, confidence interval = 0.85-0.94 left eyebrow scores) and intrarater (ICC = 0.90, confidence interval = 0.85-0.93 right eyebrow scores and ICC = 0.91, confidence interval = 0.87-0.94 left eyebrow scores) reliability. When measured in the same patient with varying degrees of hair loss over time, BETA demonstrated sensitivity to change. BETA is a simple and reliable objective assessment of eyebrow alopecia areata. BETA is easy-to-use and quick to calculate, making it feasible for a variety of clinical and research settings. Although developed for alopecia areata, we hope that BETA will be investigated in other etiologies of eyebrow alopecia to serve as a universal tool for monitoring disease progression, improvement, and response to treatment.

Digital biopiracy and the (dis)assembling of the Nagoya Protocol.

Technological leaps in DNA sequencing and synthesis are disrupting tenuous access and benefit-sharing (ABS) arrangements between 'users' and 'providers' of genetic resources. For some this signals a new era of open-source gene banks to address global challenges, but to others it threatens a new wave of unjust digital biopiracy. This paper explores the issue of digital sequence information (DSI) at the 2016 Cancun negotiations of the UN Convention on Biological Diversity and its Nagoya Protocol on ABS, and its continued relevance today. While some research has addressed potential solutions to digital sequencing and ABS, little attention has been paid to the problematization of the issue itself. This paper addresses this gap with a fine-grained view of the negotiations as an ethnographic site of contestation. We approach the Nagoya Protocol as an assemblage seeking to govern ABS. We trace how the unruly component of DSI threatens this already fragile assemblage by disrupting simplified notions of genetic resources, scientific discovery, and R&D. Our data from the negotiations reveals three major points of tension: the materiality of genetic resources; the problem's novelty; and the problem's urgency. Two opposing solutions raised in response to these contestations reveal underlying faultlines that we argue will continue to destabilise the broader ABS assemblage if left unresolved. Our attention to processes of assemblage (trans)formation offers insights to the historically fragile arrangements of ABS and, more broadly, assemblages of global environmental governance in the context of rapid technological change.

A review of occupational safety and health research for American Indians and Alaska Natives.

INTRODUCTION: To better understand what is known about issues affecting American Indian and Alaska Native (AI/AN) workers, authors conducted a literature review of publications specific to AI/AN and occupational safety and health. METHODS: Search criteria included: (a) American Indian tribes and Alaska Native villages in the United States; (b) First Nations and aboriginals in Canada; and (c) occupational safety and health. RESULTS: Results of two identical searches in 2017 and 2019 identified 119 articles and 26 articles respectively, with references to AI/AN people and occupation. Of the 145 total articles, only 11 articles met the search criteria for addressing occupational safety and health research among AI/AN workers. Information from each article was abstracted and categorized according to National Occupational Research Agenda (NORA) sector, resulting in: four articles related to agriculture, forestry, and fishing; three related to mining; one related to manufacturing; and one related to services. Two articles reported on AI/AN people and occupational well-being in general. CONCLUSIONS: The review was limited by the small number and age of relevant articles, reflecting the likelihood that findings could be out of date. General themes across the reviewed articles point to the need for increased overall awareness and education regarding injury prevention and risks associated with occupational injuries and fatalities among AI/AN workers. Similarly, increased use of personal protective equipment (PPE) is recommended for the agriculture, forestry, and fishing industries, as well as for workers exposed to metals dust. PRACTICAL APPLICATIONS: The lack of research in most NORA sectors indicates the need for heightened research efforts directed toward AI/AN workers.

Pulmonary tumour thrombotic microangiopathy mimicking immunotherapy-associated pneumonitis.

We present a case of pulmonary tumour thrombotic microangiopathy (PTTM) in a patient on adjuvant immunotherapy for resected triple negative breast cancer. The patient presented with deranged liver function tests and subsequently developed severe hypoxia and thrombocytopaenia, with right heart failure. The primary differential diagnosis considered was immunotherapy-associated hepatitis and pneumonitis. Despite organ support, the patient deteriorated rapidly and died of respiratory failure. As is often the case with PTTM, the diagnosis was only found at postmortem. PTTM should be considered in patients with a background of cancer (and may be more common in certain subtypes) who present with this unusual combination of clinical features. While the condition carries an extremely poor prognosis, prompter recognition for future patients may allow consideration of novel treatments.

The health of rural Black communities during COVID: Some affirmations, some surprises.

Background and objective: There are overwhelming health disparities in the Deep South. It is important to include the voice of communities affected by these disparities when developing interventions. The goal of the current study was to develop an academic community engaged partnership to strengthen the ability to address priority health concerns of rural African American communities with a focus on health literacy and health advocacy. Methods: A community-based participatory research approach was used to administer a 15-item community health survey in five rural communities led by African American mayors in Alabama (N = 752). The survey assessed the health concerns and the potential behaviors that may be associated with those health concerns. Results: The five communities demonstrated similarities as well as differences in both the health concerns endorsed and the potential health behaviors that may contribute to those concerns. All five communities identified cardiovascular disease as a health concern with three endorsing mental health issues and 2 dental health. With respect to behaviors, all five communities identified either unhealthy eating/exercise and substance use as concerns with one community identifying racism as a risky behavior affecting health. Conclusion: The results presented replicate CBPR studies demonstrating that communities are important sources of information about local health priorities and concerns.

The Incidence and Temporal Patterns of Use of Amphetamine-Type Stimulant Use in Traffic-Related Ambulance Attendances From 2015 to 2020 in Victoria, Australia.

OBJECTIVE: Amphetamine-type stimulants are increasingly implicated in road trauma incidents. Although ambulances are typically first to attend these emergencies, limited research has used paramedic clinical data to examine the contribution of amphetamine use to road trauma-related ambulance attendances. We describe the clinical and temporal risk profiles associated with amphetamine-related harm in road trauma incidents requiring paramedic attendance in the Australian state of Victoria. METHOD: This cross-sectional, retrospective observational study examined the Victorian component of a national surveillance data set (National Ambulance Surveillance System) of alcohol and other drug (AOD)-related ambulance attendances to determine the incidence and temporal profile of amphetamine use in traffic-related ambulance attendances from January 2015 to December 2020. RESULTS: Throughout the observation period, Victorian paramedics attended 8,163 alcohol, pharmaceutical, or illicit drug-related cases involving a road trauma. More than one quarter (2,161 cases, 27.4%) of these attendances were deemed related to the use of pharmaceutical and/or illicit drugs. Amphetamine alone was involved in nearly one third (640 cases, 29.6%) of non-alcohol-related road trauma attendances, and co-consumption of amphetamine with drugs other than alcohol occurred in more than one third (35.3%) of all AOD-related traffic incidents. Amphetamine-related road trauma attendances predominantly occurred on the weekend (Fri-Sun) during late night/early morning in metropolitan Melbourne. Between 2015 and 2020, the incidence of amphetamine-related road trauma ambulance attendances increased by 86.8%, from 1.1 per 100,000 population in 2015 to 1.9 per 100,000 population in 2020. CONCLUSIONS: Amphetamine-type stimulants are increasingly implicated in road trauma. Co-consumption with other potentially impairing substances reflects a concerning trend of polysubstance use among Victorian drivers.

Disaster preparedness of linguistically isolated populations: practical issues for planners.

In the absence of culturally and linguistically appropriate disaster preparedness plans, several linguistically isolated and culturally diverse population groups are disproportionately disadvantaged in the United States. The communication gap poses challenges to emergency preparedness planners and response personnel in predisaster communication and postdisaster response efforts. Houston Department of Health and Human Services aimed to develop practical recommendations for local emergency response personnel so as to improve dissemination of emergency information and equitable delivery of services to linguistically isolated communities in the greater Houston area. Sixteen focus group discussions were conducted among linguistically isolated immigrant populations living in the greater Houston metropolitan area who primarily spoke one of the Spanish, Chinese, Vietnamese, and Somali languages. Our questions focused on general knowledge and understanding of disasters and explored experiences during Houston's most recent disaster, Hurricane Ike. We found that (a) understanding of disaster and preparedness is contextual, (b) awareness of preparedness needs and actual plans among LIPs is inadequate, and (c) word of mouth is the preferred information source for linguistically isolated groups. Disaster preparedness plans of a given jurisdiction should reflect the culturally and linguistically appropriate components addressing the needs, concerns, context-based knowledge or awareness, and perceptions of linguistically isolated populations.

Hairstyling Practices to Prevent Hair Damage and Alopecia in Women of African Descent.

Highly textured hair has been found to be more susceptible to breakage than other hair types due to an increased proportion of spirals and relatively fewer elastic fibers anchoring the hair follicles to the dermis. Women of African descent frequently employ hairstyles and hair treatments for ease of management and as a form of self-expression, but a number of these practices have been implicated as risk factors for alopecia. Herein, we provide an overview of hairstyles for patients with highly textured hair so that physicians may better identify high-risk hairstyles, provide individualized recommendations for safer alternatives, and manage and stop the progression of hair loss before it becomes permanent.

Identifying Points of Prevention in Firearm-Related Suicides: A Mixed-Methods Study Based on Coronial Records.

PURPOSE: Firearm-related suicide is a noteworthy and preventable public health issue that has drawn limited attention in Australian research. Firearms are highly lethal and remain in the top three methods of suicide among Australian males. This study examines suicides occurring in Tasmania, the jurisdiction with the highest rate of firearm-related suicide, with the aim of aiding suicide prevention strategies. METHODS: A mixed-methods approach was used to analyze data from the Tasmanian Suicide Register. The quantitative analysis examined socio-demographic factors, substance use, physical and mental health, and access to services for suicides occurring between January 1, 2012 and December 31, 2016. The qualitative analysis comprised firearm-related suicides occurring between January 1, 2012 and December 31, 2017. RESULTS: Firearms users were more likely than those employing other means of suicide to be male, retired, and residing in remote areas but were less likely to have had a previous mental illness diagnosis or evidence of suicidal ideation or self-harming behaviors. There was some evidence of increased impulsiveness among firearm users. We found 54% of decedents were licensed to own a firearm at the time of death. Firearms most often belonged to the decedent (52%) and 26% sourced a firearm from family or friends. Only 58% of cases involved a firearm with a dedicated storage facility. CONCLUSIONS: Prevention efforts need to take into account the unique profiles of those at risk of firearm-related suicide. Impulsiveness and the varying levels of adherence to firearms safety practices point to the need for strategies that limit physical access to firearms.HIGHLIGHTSFirearms-related suicides have a unique risk profile compared with other means of suicide.Mental illness diagnosis, suicidal thoughts, and self-harming behaviors were less commonly identified among firearms-related suicides than other means of suicide.Impulsiveness and the varying levels of adherence to firearms safety practices point to the need for strategies that limit physical access to firearms.

Services and Challenges at a Native American Residential Substance Use Disorder Treatment Center during the COVID-19 Pandemic.

During the COVID-19 pandemic, challenges arose for a Native American residential substance use disorder treatment program in California (e.g., insufficient housing for quarantining, inadequate telehealth bandwidth, food shortages, client skepticism regarding safety needs). These challenges were addressed, culturally appropriate services continued, no clients tested positive for COVID-19, and unexpected benefits arose.

Republished paper: Emergency department triage revisited.

Triage is a process that is critical to the effective management of modern emergency departments. Triage systems aim, not only to ensure clinical justice for the patient, but also to provide an effective tool for departmental organisation, monitoring and evaluation. Over the last 20 years, triage systems have been standardised in a number of countries and efforts made to ensure consistency of application. However, the ongoing crowding of emergency departments resulting from access block and increased demand has led to calls for a review of systems of triage. In addition, international variance in triage systems limits the capacity for benchmarking. The aim of this paper is to provide a critical review of the literature pertaining to emergency department triage in order to inform the direction for future research. While education, guidelines and algorithms have been shown to reduce triage variation, there remains significant inconsistency in triage assessment arising from the diversity of factors determining the urgency of any individual patient. It is timely to accept this diversity, what is agreed, and what may be agreeable. It is time to develop and test an International Triage Scale (ITS) which is supported by an international collaborative approach towards a triage research agenda. This agenda would seek to further develop application and moderating tools and to utilise the scales for international benchmarking and research programmes.

Identifying work related injuries: comparison of methods for interrogating text fields.

BACKGROUND: Work-related injuries in Australia are estimated to cost around $57.5 billion annually, however there are currently insufficient surveillance data available to support an evidence-based public health response. Emergency departments (ED) in Australia are a potential source of information on work-related injuries though most ED's do not have an 'Activity Code' to identify work-related cases with information about the presenting problem recorded in a short free text field. This study compared methods for interrogating text fields for identifying work-related injuries presenting at emergency departments to inform approaches to surveillance of work-related injury. METHODS: Three approaches were used to interrogate an injury description text field to classify cases as work-related: keyword search, index search, and content analytic text mining. Sensitivity and specificity were examined by comparing cases flagged by each approach to cases coded with an Activity code during triage. Methods to improve the sensitivity and/or specificity of each approach were explored by adjusting the classification techniques within each broad approach. RESULTS: The basic keyword search detected 58% of cases (Specificity 0.99), an index search detected 62% of cases (Specificity 0.87), and the content analytic text mining (using adjusted probabilities) approach detected 77% of cases (Specificity 0.95). CONCLUSIONS: The findings of this study provide strong support for continued development of text searching methods to obtain information from routine emergency department data, to improve the capacity for comprehensive injury surveillance.

Emergency department triage revisited.

Triage is a process that is critical to the effective management of modern emergency departments. Triage systems aim, not only to ensure clinical justice for the patient, but also to provide an effective tool for departmental organisation, monitoring and evaluation. Over the last 20 years, triage systems have been standardised in a number of countries and efforts made to ensure consistency of application. However, the ongoing crowding of emergency departments resulting from access block and increased demand has led to calls for a review of systems of triage. In addition, international variance in triage systems limits the capacity for benchmarking. The aim of this paper is to provide a critical review of the literature pertaining to emergency department triage in order to inform the direction for future research. While education, guidelines and algorithms have been shown to reduce triage variation, there remains significant inconsistency in triage assessment arising from the diversity of factors determining the urgency of any individual patient. It is timely to accept this diversity, what is agreed, and what may be agreeable. It is time to develop and test an International Triage Scale (ITS) which is supported by an international collaborative approach towards a triage research agenda. This agenda would seek to further develop application and moderating tools and to utilise the scales for international benchmarking and research programmes.

Self-reported sleep disturbance in ambulance attendances for suicidal ideation and attempted suicide between 2012 and 2017.

BACKGROUND: Sleep disturbances are among the top-ten warning signs for suicide, however there has been limited investigation of the relationship between these variables in acute presentations, particularly community settings. We examined ambulance attendances for suicide ideation and attempt to explore the role of sleep and co-morbid factors (mental health symptoms, attendance time, and alcohol and benzodiazepine use). METHODS: Coded clinical records from Ambulance Victoria for the period 1 January 2012 to 30 June 2017 were analysed. RESULTS: Paramedics attended 97,198 cases of suicidal ideation or suicide attempt during the study period. Just over half (56.4%) of these were for suicidal ideation, and 43.6% were for attempted suicide. Depression symptomology-related attendances were more common than those for anxiety and despite a lower proportion of both sleep and current anxiety-related symptoms, benzodiazepine use was significantly more common in attendances for suicide attempts (25.9%) than for ideation (2.2%). Co-morbid benzodiazepine use was associated with attempted suicide (OR: 10.37 (10.04-10.72), in a hierarchical regression model. LIMITATIONS: Data represent self-report/paramedic observation only, and do include validated measures of sleep or drug use. Sleep disturbance is likely under recorded in ambulance attendances given the primary role of paramedics is to stabilise patients, and minimise risk of harm during transport. CONCLUSION: This study reports internationally unique data, and provides the first examination of ambulance coded clinical records for suicide ideation and attempt. Sleep disturbances had a unique role in these attendances, over and above common co-occurring factors including drug use and mental health diagnoses.

Bioengineering horizon scan 2020.

Horizon scanning is intended to identify the opportunities and threats associated with technological, regulatory and social change. In 2017 some of the present authors conducted a horizon scan for bioengineering (Wintle et al., 2017). Here we report the results of a new horizon scan that is based on inputs from a larger and more international group of 38 participants. The final list of 20 issues includes topics spanning from the political (the regulation of genomic data, increased philanthropic funding and malicious uses of neurochemicals) to the environmental (crops for changing climates and agricultural gene drives). The early identification of such issues is relevant to researchers, policy-makers and the wider public.

Community-based strategies for recruiting older, African Americans into a behavioral intervention study.

PURPOSE: To describe community-based strategies that were effective in recruiting older African Americans into a behavioral intervention study designed to increase eye examination behavior. METHODS: Sites were identified that targeted older African-Americans, including senior centers, senior housing, and church groups. We conducted presentations at these sites, networked with community organizations, placed ads on the radio and in newspapers, and attended health fairs. Potential participants also called us in response to flyers and through word of mouth. RESULTS: We conducted 147 activities at 118 sites. A total of 688 potential participants were screened, with 330 (48%) enrolling, 33% ineligible, and 19% not interested. Highest enrollment rates were for word of mouth (69%), flyers (67%), and senior centers (66%). Barriers to participation included hesitancy of seniors to leave their apartments to attend presentations and competing health issues taking precedence over eye concerns. CONCLUSIONS: A multifaceted recruitment approach incorporating both direct and indirect activities at a variety of sites should be used to recruit older African Americans into a behavioral intervention study. Establishing relationships in the community, both prior to initiating recruitment activities and as an ongoing process, was important to the study's success.