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1.
BMC Health Serv Res ; 24(1): 492, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643146

RESUMO

BACKGROUND: Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. METHODS: A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman's multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. RESULTS: Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of 'accessible and timely', 'person-centred', and values of 'dignity and respect' and 'kindness with compassion' were most prevalent. Among the three patient experience surveys identified, 'accessible and timely' and 'person-centred' were the most frequent domains. The least frequently highlighted domains and values were 'equitable' and 'holistic'. No questions addressed the 'safety' domain. CONCLUSIONS: The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of 'Kindness and compassion' require further emphasis when seeking feedback on healthcare experiences and the domains of 'safety', 'equitable', and 'efficiency' are not adequately represented in existing patient experience surveys.


Assuntos
Atenção à Saúde , Pessoas Mal Alojadas , Humanos , Problemas Sociais , Pesquisa Qualitativa , Avaliação de Resultados da Assistência ao Paciente
2.
Emerg Med Australas ; 35(6): 903-920, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37788821

RESUMO

As a result of climate change heatwaves are expected to increase in frequency and intensity and will have detrimental impacts on human health globally. EDs are often the critical point of care for acute heat illnesses and other conditions associated with heat exposure. Existing literature has focused on heatwave-related hospitalisation and mortality. This scoping review aimed to identify, evaluate and summarise current literature regarding patient characteristics and outcomes of ED admissions from heatwaves. A scoping review of the literature was conducted using six databases: Medline, EMBASE, EMCARE, CINAHL, PsycINFO, and Scopus, using MeSH terms and keywords related to 'heatwave' and 'Emergency Department'. Articles were included if they were: published in English from January 2000 to August 2021, related to ED, and examined high temperature periods consistent with heatwave criteria. Articles were appraised using the Mixed Methods Appraisal Tool (MMAT). Thirty-one studies were included, mostly from the United States, Australia, and France. The study designs include retrospective case analysis, case-control, and time-series analysis. Eight studies examined known heatwaves, 21 used different criteria to identify heatwave occurrence, and two focused on heat-related illness. The selected articles display a moderate-high quality on MMAT. ED admissions for both heat-related illnesses and other conditions increased during heatwaves, with up to 18.5 times risk increase. The risk was elevated for all population groups, and substantially in the elderly, male patients with certain comorbidities, medications, or lower socioeconomic status. Outcomes including hospitalisation and mortality rates after ED admissions showed positive associations with heatwaves. The heatwaves resulting from climate change will place increasing demands on EDs providing care for increasingly susceptible populations. Significant public heatwave planning across multiple sectors is required to reduce the risk of overwhelming EDs with these patients.


Assuntos
Serviço Hospitalar de Emergência , Hospitalização , Humanos , Masculino , Adulto , Idoso , Estudos Retrospectivos , Austrália/epidemiologia , Mudança Climática
3.
Artigo em Inglês | MEDLINE | ID: mdl-36767794

RESUMO

The ED is often the first and sometimes the only place where people experiencing homelessness seek medical assistance. While access to primary healthcare is a preferable and more cost-effective alternative to ED, for many reasons, people experiencing homelessness are much less likely to have a regular General Practitioner compared to those living in stable accommodation. Drawing on a growing body of emergency care and homelessness literature and practice, we have synthesised four potential interventions to optimise access to care when people experiencing homelessness present to an ED. Although EDs are in no way responsible for resolving the complex health and social issues of their local homeless population, they are a common contact point and therefore present an opportunity to improve access to healthcare.


Assuntos
Atenção à Saúde , Pessoas Mal Alojadas , Humanos , Problemas Sociais , Serviço Hospitalar de Emergência , Hospitais
4.
Int J Epidemiol ; 52(2): 501-511, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-36752734

RESUMO

BACKGROUND: People experiencing homelessness have an increased risk of mortality. The association between being at risk of homelessness and premature mortality is unclear. We aimed to determine all-cause and cause-specific mortality in patients who were homeless, at risk of homelessness (marginally housed), or housed. METHODS: This retrospective longitudinal cohort study compared mortality patterns in adult patients identified in 2003/04 by linking data from an Australian metropolitan emergency department to national mortality data. We used Cox proportional hazards models to estimate associations between housing status and mortality. To address competing risks, cause-specific hazards were modelled and transformed into stacked cumulative incidence functions. FINDINGS: Data from 6290 patients (homeless deceased = 382/1050, marginally housed deceased = 259/518, housed deceased = 1204/4722) found increased risk of mortality in homeless [hazard ratio (HR) = 4.0, 95% confidence interval (CI) = 2.0-3.3) and marginally housed (HR = 2.6, 95% CI = 3.4-4.8) patients. Homeless patients had an excess risk from external causes (HR = 6.1, 95% CI = 4.47-8.35), cardiovascular disease (HR = 4.9, 95% CI = 2.78-8.70) and cancer (HR = 1.5, 95% CI = 1.15-2.09). Marginally housed patients had increased risk from external causes (HR = 3.6, 95% CI = 2.36-5.40) and respiratory diseases (HR = 4.7, 95% CI = 1.82-12.05). Taking account of competing risk, marked inequality was observed, with homeless, marginally housed and housed patients having probabilities of death by 55 years of 0.2, 0.1 and 0.02, respectively. CONCLUSIONS: Mortality rates were elevated in patients who were homeless or at risk of homelessness. Increasing numbers of people are at risk of homelessness, and the effect of this on mortality is relatively unrecognized. Marginal housing may assuage some risk of premature mortality associated with homelessness; however, it is not equivalent to stable housing.


Assuntos
Pessoas Mal Alojadas , Mortalidade Prematura , Humanos , Adulto , Estudos Longitudinais , Estudos Retrospectivos , Austrália/epidemiologia , Habitação , Serviço Hospitalar de Emergência
5.
Emerg Med Australas ; 35(1): 74-81, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36041727

RESUMO

OBJECTIVE: Using a strength-based framework, we aimed to describe and compare First Nations patients who completed care in an ED to those who took their own leave. METHODS: Routinely collected adult patient data from a metropolitan ED collected over a 5-year period were analysed. RESULTS: A total of 6446 presentations of First Nations patients occurred from 2016 to 2020, constituting 3% of ED presentations. Of these, 5589 (87%) patients waited to be seen and 857 (13%) took their own leave. Among patients who took their own leave, 624 (73%) left not seen and 233 (27%) left at own risk after starting treatment. Patients who were assigned a triage category of 4-5 were significantly more likely to take their own leave (adjusted odds ratio [OR] 3.17, 95% confidence interval [CI] 2.67-3.77, P < 0.001). Patients were significantly less likely to take their own leave if they were >60 years (adjusted OR 0.69, 95% CI 1.01-1.36, P = 0.014) and had private health insurance (adjusted OR 0.61, 95% CI 0.45-0.84, P < 0.001). Patients were more likely to leave if they were women (adjusted OR 1.17, 95% CI 1.01-1.36, P = 0.04), had an unknown housing status (adjusted OR 1.76, 95% CI 1.44-2.15, P < 0.001), were homeless (adjusted OR 1.50, 95% CI 1.22-1.93, P < 0.001) or had a safety alert (adjusted OR 1.60, 95% CI 1.35-1.90, P < 0.001). CONCLUSION: A lower triage category is a strong predictor of First Nations patients taking their own leave. It has been documented that First Nations patients are under-triaged. One proposed intervention in the metropolitan setting is to introduce practices which expediate the care of First Nations patients. Further qualitative studies with First Nations patients should be undertaken to determine successful approaches to create equitable access to emergency healthcare for this population.


Assuntos
Serviço Hospitalar de Emergência , Triagem , Adulto , Humanos , Feminino , Masculino , Fatores de Tempo , Pacientes , Estudos Retrospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-36554443

RESUMO

Extreme heat and hot weather has a negative impact on human health and society. Global warming has resulted in an increase in the frequency and duration of heatwaves. Heat-related illnesses are a significant negative consequence of high temperatures and can be life-threatening medical emergencies. The severity of the symptoms can depend on the pre-existing medical conditions and vary from mild headaches to severe cases that can lead to coma and death. The risk of heat-related illness may be higher for people experiencing homelessness due to a lack of access to cool places and water, and the complex interactions between mental illness, medications and substance use disorder. This paper presents two cases of people experiencing homelessness who were admitted to the emergency department of a hospital in Sydney, Australia during a heatwave in November 2020. Both cases were adult males with known risk factors for heat-related illness including hypertension and schizophrenia (Case One) and hepatitis C, cirrhosis, and alcohol use disorder (Case Two). These cases show that severe weather can not only be detrimental to homeless people's health but can also cause a significant economic toll, evident by the $70,184 AUD expenditure on the care for these two cases. This case report highlights the requirement to determine the risk of heat-related illness to people experiencing homelessness and need to protect this vulnerable population from weather-related illness and death.


Assuntos
Transtornos de Estresse por Calor , Pessoas Mal Alojadas , Masculino , Adulto , Humanos , Tempo (Meteorologia) , Temperatura Alta , Serviço Hospitalar de Emergência
8.
Emerg Med Australas ; 34(4): 644-647, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35483709

RESUMO

The ED at St Vincent's Hospital Melbourne aims to provide excellent emergency care and cultural safety for Aboriginal and Torres Strait Islander peoples. High rates of people who 'Left Not Seen' and some negative experiences of care led us to improve our performance in this area. Collective desire and strong executive support generated the ED Indigenous Health Equity Working Group (IHEWG) project. This was co-led by both the ED and the Aboriginal Health Unit (AHU). A strengths-based participatory methodology and fortnightly virtual meetings were established to generate ideas for short- and long-term reforms. Initial outcomes have included a focus on cultural safety and trauma-informed care education. Further projects included improving identification processes, creating a welcoming waiting-room environment and fostering strong relationships between the ED and AHU. We have begun our ED journey towards equity and excellent care for Aboriginal and Torres Strait Islander people, hoping this collaborative model will enable transformative change.


Assuntos
Serviços de Saúde do Indígena , Competência Cultural , Serviço Hospitalar de Emergência , Humanos , Povos Indígenas , Havaiano Nativo ou Outro Ilhéu do Pacífico
9.
Emerg Med Australas ; 34(4): 509-518, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35021268

RESUMO

OBJECTIVE: Although most unintentional opioid deaths in Australia are attributed to pharmaceutical opioids, take-home naloxone (THN) programmes have to date predominantly targeted people using illicit opioids in drug treatment and harm reduction settings. We sought to examine the feasibility of delivering THN brief interventions (THN-BIs) with intranasal naloxone in EDs. METHODS: This pilot feasibility study was conducted across three major metropolitan EDs in Sydney and Melbourne. ED staff were surveyed about their perspectives regarding THN before completing a 30-min training programme in THN-BI delivery. Patients presenting with opioid overdose or considered high risk for future overdose were eligible to receive the THN-BI. Staff survey responses were compared between hospitals and provider types using one-way analysis of variances. Patient demographic and clinical characteristics were extracted from medical records and compared between hospitals and overdose type using Fisher's exact test and one-way analysis of variances. RESULTS: One hundred and twenty-two ED staff completed the survey. One hundred and ten (90.2%) agreed that EDs should provide THN-BIs, whereas 23 (19.2%) identified time constraints and 17 (12.9%) felt uncomfortable discussing overdose with patients. Fifty-seven patients received the THN-BI, with the majority (n = 50, 87.7%) having presented following opioid overdose. The median age was 44 years and 40 (71.4%) were men. Two-thirds of the overdoses (n = 31, 66.0%) were attributed to heroin with one-third (n = 16, 34%) being attributed to pharmaceutical opioids. CONCLUSIONS: ED-based delivery of THN-BIs can reach a wide range of individuals at-risk of overdose. The present study supports the feasibility of THN interventions in EDs and underscores the importance of addressing implementation barriers including staff training.


Assuntos
Overdose de Drogas , Overdose de Opiáceos , Adulto , Analgésicos Opioides/uso terapêutico , Intervenção em Crise , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/prevenção & controle , Serviço Hospitalar de Emergência , Estudos de Viabilidade , Feminino , Humanos , Masculino , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Preparações Farmacêuticas , Projetos Piloto
10.
Chembiochem ; 23(1): e202100463, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34647407

RESUMO

Vascular endothelial growth factors (VEGFs) regulate significant pathways in angiogenesis, myocardial and neuronal protection, metabolism, and cancer progression. The VEGF-B growth factor is involved in cell survival, anti-apoptotic and antioxidant mechanisms, through binding to VEGF receptor 1 and neuropilin-1 (NRP1). We employed surface plasmon resonance technology and X-ray crystallography to analyse the molecular basis of the interaction between VEGF-B and the b1 domain of NRP1, and developed VEGF-B C-terminus derived peptides to be used as chemical tools for studying VEGF-B - NRP1 related pathways. Peptide lipidation was used as a means to stabilise the peptides. VEGF-B-derived peptides containing a C-terminal arginine show potent binding to NRP1-b1. Peptide lipidation increased binding residence time and improved plasma stability. A crystal structure of a peptide with NRP1 demonstrated that VEGF-B peptides bind at the canonical C-terminal arginine binding site. VEGF-B C-terminus imparts higher affinity for NRP1 than the corresponding VEGF-A165 region. This tight binding may impact on the activity and selectivity of the full-length protein. The VEGF-B167 derived peptides were more effective than VEGF-A165 peptides in blocking functional phosphorylation events. Blockers of VEGF-B function have potential applications in diabetes and non-alcoholic fatty liver disease.


Assuntos
Neuropilina-1/metabolismo , Peptídeos/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Humanos , Neuropilina-1/química , Peptídeos/química , Ligação Proteica , Fator B de Crescimento do Endotélio Vascular/química
12.
Emerg Med J ; 39(5): 386-393, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34433615

RESUMO

OBJECTIVE: Patients, families and community members would like emergency department wait time visibility. This would improve patient journeys through emergency medicine. The study objective was to derive, internally and externally validate machine learning models to predict emergency patient wait times that are applicable to a wide variety of emergency departments. METHODS: Twelve emergency departments provided 3 years of retrospective administrative data from Australia (2017-2019). Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine learning models were developed to predict wait times at each site and were internally and externally validated. Model performance was tested on COVID-19 period data (January to June 2020). RESULTS: There were 1 930 609 patient episodes analysed and median site wait times varied from 24 to 54 min. Individual site model prediction median absolute errors varied from±22.6 min (95% CI 22.4 to 22.9) to ±44.0 min (95% CI 43.4 to 44.4). Global model prediction median absolute errors varied from ±33.9 min (95% CI 33.4 to 34.0) to ±43.8 min (95% CI 43.7 to 43.9). Random forest and linear regression models performed the best, rolling average models underestimated wait times. Important variables were triage category, last-k patient average wait time and arrival time. Wait time prediction models are not transferable across hospitals. Models performed well during the COVID-19 lockdown period. CONCLUSIONS: Electronic emergency demographic and flow information can be used to approximate emergency patient wait times. A general model is less accurate if applied without site-specific factors.


Assuntos
COVID-19 , Medicina de Emergência , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Triagem , Listas de Espera
13.
Ann Emerg Med ; 78(1): 113-122, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33972127

RESUMO

STUDY OBJECTIVE: To derive and internally and externally validate machine-learning models to predict emergency ambulance patient door-to-off-stretcher wait times that are applicable to a wide variety of emergency departments. METHODS: Nine emergency departments provided 3 years (2017 to 2019) of retrospective administrative data from Australia. Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine-learning models were developed to predict wait times at each site and were internally and externally validated. RESULTS: There were 421,894 episodes analyzed, and median site off-load times varied from 13 (interquartile range [IQR], 9 to 20) to 29 (IQR, 16 to 48) minutes. The global site prediction model median absolute errors were 11.7 minutes (95% confidence interval [CI], 11.7 to 11.8) using linear regression and 12.8 minutes (95% CI, 12.7 to 12.9) using elastic net. The individual site model prediction median absolute errors varied from the most accurate at 6.3 minutes (95% CI, 6.2 to 6.4) to the least accurate at 16.1 minutes (95% CI, 15.8 to 16.3). The model technique performance was the same for linear regression, random forests, elastic net, and rolling average. The important variables were the last k-patient average waits, triage category, and patient age. The global model performed at the lower end of the accuracy range compared with models for the individual sites but was within tolerable limits. CONCLUSION: Electronic emergency demographic and flow information can be used to estimate emergency ambulance patient off-stretcher times. Models can be built with reasonable accuracy for multiple hospitals using a small number of point-of-care variables.


Assuntos
Ambulâncias/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Aprendizado de Máquina , Tempo para o Tratamento/estatística & dados numéricos , Austrália , Humanos , Estudos Retrospectivos
14.
Emerg Med Australas ; 33(3): 425-433, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32985795

RESUMO

OBJECTIVE: EDs have the potential ability to predict patient wait times and to display this to patients and other stakeholders. Little is known about whether consumers and stakeholders would want this information and how wait time predictions might be used. The aim of the present study was to gain perspectives from consumers and health services personnel regarding the concept of emergency wait time visibility. METHODS: We conducted a qualitative interview and focus group study in 2019. Participants included emergency medicine patients, families, paramedics, well community members, and hospital/paramedic administrators from multiple EDs and organisations in Victoria, Australia. Transcripts were coded and themes presented. RESULTS: One focus group and 103 semi-structured interviews were conducted in 2019 including 32 patients, 22 carers/advocates and 21 paramedics in the ED; 20 health service administrators (paramedic and hospital) and 15 community members. Consumers and paramedics face physical and psychological difficulties when wait times are not visible. Consumers believe about a 2-h wait is tolerable, beyond this most begin to consider alternative strategies for seeking care. Consumers want to see triage to doctor times; paramedics want door-to-off stretcher times (for all possible transport destinations); with 47 of 50 consumers and 30 of 31 paramedics potentially using this information. About 28 of 50 consumers would use times to inform facility or provider choice, another 19 of 50 want information once in the waiting room. During prolonged waits, 51 of 52 consumers would continue to seek care. CONCLUSIONS: Consumers and paramedics want wait time information visibility. They would use the information in a variety of ways, both pre-hospital and while waiting for care.

15.
Emerg Med Australas ; 33(1): 9-18, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33248447

RESUMO

Aboriginal and Torres Strait Islander peoples continue to suffer adverse experiences in healthcare, with inequitable care prevalent in emergency settings. Individual, institutional and systemic factors play a significant part in these persisting healthcare disparities, with biases remaining entrenched in healthcare institutions. This includes implicit racial bias which can result in stereotyping of racial minorities and premature diagnostic closure. Furthermore, it may contribute to distrust of medical professionals resulting in higher rates of leave events and hinder racial minorities from seeking care or following treatment recommendations. The aim of this review is to analyse the effect of implicit bias on patient outcomes in the ED in international literature and explore how these studies correlate to an Australian context.


Assuntos
Havaiano Nativo ou Outro Ilhéu do Pacífico , Preconceito , Austrália , Serviço Hospitalar de Emergência , Disparidades em Assistência à Saúde , Humanos
16.
Emerg Med Australas ; 32(6): 924-934, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33089635

RESUMO

Opioid-related harms have been increasing in Australia over the last 5 years. Patients with opioid use disorder are over-represented in ED presentations. Opioid agonist treatment is the most effective community-based treatment. Buprenorphine is considered the safest of these treatments to use in the ED setting. This rapid review investigated the effectiveness of initiating buprenorphine in the ED setting. Medline, Embase, Emcare, PSYCinfo, CINAHL and Cochrane Central Register of Controlled Trials databases were searched. Randomised and non-randomised studies published in peer-reviewed journals that involved the initiation of buprenorphine in the ED setting were considered eligible. The search revealed 350 articles of which 11 were included in the review; three articles representing two randomised controlled trials (RCTs) and eight observational studies. Data were extracted from included papers and risk of bias assessed on the RCTs. One well-conducted RCT showed that buprenorphine initiated in the ED does improve treatment engagement up to 2 months after an ED visit. Eight observational studies, one with a comparator group reported positive results for this intervention. There is strong evidence that clinicians should consider commencing buprenorphine in the ED for patients with opioid use disorder when combined with a direct and supported referral or 'warm handover' to community care. Further implementation studies and investigation of long-acting injectable buprenorphine treatment are required.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Serviço Hospitalar de Emergência , Humanos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
17.
Emerg Med Australas ; 32(6): 1084-1086, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32959470

RESUMO

Homeless individuals face many barriers to accessing healthcare, and EDs are often their primary entry point to the healthcare system. The COVID-19 pandemic has the potential to exacerbate existing social inequities and health disparities, including barriers to accessing social services and healthcare. Addressing the complex social and chronic health issues associated with homelessness can be challenging within the acute care environment. This perspective reflects upon the delivery of emergency healthcare to patients experiencing homelessness, and highlights strategies for optimising health outcomes during and beyond the pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Serviços Médicos de Emergência , Pessoas Mal Alojadas , Pneumonia Viral/epidemiologia , Adulto , Austrália/epidemiologia , COVID-19 , Infecções por Coronavirus/terapia , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/organização & administração , Feminino , Disparidades em Assistência à Saúde , Humanos , Masculino , Pandemias , Pneumonia Viral/terapia
18.
Aust N Z J Public Health ; 44(6): 476-481, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32955766

RESUMO

OBJECTIVE: To examine the effect of homelessness on mortality. METHODS: This 15-year retrospective longitudinal cohort study compared mortality outcomes of homeless and non-homeless adults attending the emergency department of an inner-city public hospital in Melbourne, Victoria between 1 January 2003 and 31 December 2004. Homeless individuals had ≥1 recorded episodes of homelessness within the recruitment period, categorised by type: primary, secondary, tertiary, marginally housed. Non-homeless individuals were stably housed throughout. RESULTS: Over 15 years, homeless individuals had a higher mortality rate (11.89 vs. 8.10 per 1,000 person-years), significantly increased mortality risk (rate ratio 1.47, 95% confidence interval [CI] 1.26-1.71) and younger median age at death (66.60 vs. 78.19 years) compared to non-homeless individuals. Using adjusted Cox proportional hazards models, primary (hazard ratio [HR] 2.05, 95%CI 1.67-2.50), secondary (HR 1.60, 95%CI 1.23-2.10) and tertiary (HR 1.72, 95%CI 1.16-2.56) homelessness were independent risk factors for premature mortality. CONCLUSION: At least one recorded episode of primary, secondary, or tertiary homelessness was associated with premature mortality and younger age at death over a 15-year period. Implications for public health: Accurately identifying individuals experiencing primary, secondary or tertiary homelessness at the emergency department may enable targeted interventions that could potentially reduce their risk of premature mortality.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Habitação , Pessoas Mal Alojadas/estatística & dados numéricos , Mortalidade , Adulto , Austrália/epidemiologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Problemas Sociais , Fatores de Tempo
19.
J Med Chem ; 63(14): 7740-7765, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32575985

RESUMO

The leishmaniases, caused by Leishmania species of protozoan parasites, are neglected tropical diseases with millions of cases worldwide. Current therapeutic approaches are limited by toxicity, resistance, and cost. N-Myristoyltransferase (NMT), an enzyme ubiquitous and essential in all eukaryotes, has been validated via genetic and pharmacological methods as a promising anti-leishmanial target. Here we describe a comprehensive structure-activity relationship (SAR) study of a thienopyrimidine series previously identified in a high-throughput screen against Leishmania NMT, across 68 compounds in enzyme- and cell-based assay formats. Using a chemical tagging target engagement biomarker assay, we identify the first inhibitor in this series with on-target NMT activity in leishmania parasites. Furthermore, crystal structure analyses of 12 derivatives in complex with Leishmania major NMT revealed key factors important for future structure-guided optimization delivering IMP-105 (43), a compound with modest activity against Leishmania donovani intracellular amastigotes and excellent selectivity (>660-fold) for Leishmania NMT over human NMTs.


Assuntos
Aciltransferases/antagonistas & inibidores , Antiprotozoários/farmacologia , Inibidores Enzimáticos/farmacologia , Proteínas de Protozoários/antagonistas & inibidores , Pirimidinas/farmacologia , Tiofenos/farmacologia , Aciltransferases/química , Aciltransferases/metabolismo , Antiprotozoários/síntese química , Antiprotozoários/metabolismo , Sítios de Ligação , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Leishmania donovani/enzimologia , Leishmania major/enzimologia , Estrutura Molecular , Testes de Sensibilidade Parasitária , Ligação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Pirimidinas/síntese química , Pirimidinas/metabolismo , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/metabolismo
20.
Bioorg Med Chem ; 27(20): 114962, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307763

RESUMO

The global emergence of antibiotic resistance is one of the most serious challenges facing modern medicine. There is an urgent need for validation of new drug targets and the development of small molecules with novel mechanisms of action. We therefore sought to inhibit bacterial DNA repair mediated by the AddAB/RecBCD protein complexes as a means to sensitize bacteria to DNA damage caused by the host immune system or quinolone antibiotics. A rational, hypothesis-driven compound optimization identified IMP-1700 as a cell-active, nanomolar potency compound. IMP-1700 sensitized multidrug-resistant Staphylococcus aureus to the fluoroquinolone antibiotic ciprofloxacin, where resistance results from a point mutation in the fluoroquinolone target, DNA gyrase. Cellular reporter assays indicated IMP-1700 inhibited the bacterial SOS-response to DNA damage, and compound-functionalized Sepharose successfully pulled-down the AddAB repair complex. This work provides validation of bacterial DNA repair as a novel therapeutic target and delivers IMP-1700 as a tool molecule and starting point for therapeutic development to address the pressing challenge of antibiotic resistance.


Assuntos
Antibacterianos/farmacologia , DNA Bacteriano/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Quinolonas/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Reparo do DNA , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolonas/síntese química , Quinolonas/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
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