First stroke incidence, causes, treatments, and outcomes for Aboriginal Peoples in South Australia and the Northern Territory: a pilot prospective study.

OBJECTIVE: We performed a pilot stroke incidence study, focused on feasibility and inclusion of the CONSIDER reporting guidelines, to model the design of a future population-based study aiming to definitively determine stroke incidence, antecedents, treatment, and outcomes. STUDY DESIGN: Prospective stroke incidence study (pilot study). SETTING, PARTICIPANTS: All people aged 15 years or older who lived in postcode-defined areas of South Australia and Northern Territory (885 472 people, including 45 127 Aboriginal people [5.1%]) diagnosed with stroke for the first time during 1 October - 31 December 2015 and admitted to public hospitals or stroke and transient ischaemic attack clinics. MAIN OUTCOME MEASURES: Feasibility of a prospective population-based stroke incidence study. RESULTS: Of the 123 participants with first strokes, ten were Aboriginal (8%); the median age of Aboriginal people was 45 years (interquartile range [IQR], 33-55 years), of non-Indigenous people 73 years (IQR, 62-84 years). For Aboriginal people, the age-standardised incidence of stroke was 104 (95% confidence interval [CI], 84-124) per 100 000 person-years, for non-Indigenous people 33 (95% CI, 22-44) per 100 000 person-years. We found that a prospective population-based stroke incidence study in Aboriginal people was feasible, including with respect to establishing an adequate sample size, diagnostic confirmation, identification of incident stroke, confirming stroke subtypes, establishing a stable statistical population, standardising data reporting for comparison with other stroke incidence studies, and ethical research reporting that conforms to CONSIDER guidelines. CONCLUSIONS: A larger, population-based study of the incidence of stroke in Aboriginal people is both feasible and needed to provide robust estimates of stroke incidence, antecedents, treatments and outcomes to help guide strategies for reducing the risk of and outcomes of stroke in Aboriginal people.

Pulmonary Hypertension in Central Australia: A Community-Based Cohort Study.

BACKGROUND: The burden of pulmonary hypertension (PHT) in Central Australia has not been previously studied. Our aim is to characterise the prevalence, clinical classification, and long-term survival of individuals with PHT in Central Australia. METHODS: A community-based cohort study of all individuals diagnosed with PHT in Central Australia between 2005 and 2016 was undertaken. We estimated PHT prevalence using population data, describe clinical PHT classification, and characterised long-term survival using Kaplan-Meier approaches. RESULTS: A total of 183 patients were identified (mean age 52±16years, 63% female). Of these individuals, 149 (81.4%) were of Aboriginal and Torres Strait Islander (ATSI) descent. The prevalence per 100,000 of any PHT was significantly higher In ATSI (723 [95% CI 608-839] compared to non-ATSI individuals (126 [95% CI 84-168], p<0.001). Furthermore, ATSI individuals were diagnosed at younger ages compared to non-ATSI individuals (49±15 vs 64±16years, p<0.001). Median estimated pulmonary artery systolic pressure (ePASP) was higher in patients with pulmonary arterial hypertension (PAH) compared to other causes (62 [IQR 54-69] vs 50 [IQR 44-58] mmHg, p<0.01). The median survival rate from diagnosis was 9 years (IQR 7.2-13.2). Age and ePASP were significant predictors of mortality (HR 1.05 [95% CI 1.02-1.07] and HR 1.56 [95% 1.00-2.42] respectively). CONCLUSIONS: In this community based study, we found a high burden of PHT in Central Australia. The prevalence of PHT is greater in ATSI individuals and is diagnosed at younger ages compared to non-ATSI individuals. Together with other cardiovascular diseases, PHT may be in-part contributing to the gap in life expectancy between ATSI and non-ATSI individuals.

Pattern and Outcome of Heart Failure-Related Hospitalization Over 5 Years in a Remote Australian Population: A Retrospective Administrative Data Cohort of 617 Indigenous and non-Indigenous Cases.

OBJECTIVE: The aim of this work was to understand the pattern and outcomes for heart failure (HF)-related hospitalization among Indigenous and non-Indigenous patients living in Central Australia. METHODS AND RESULTS: A retrospective analysis of administrative data for patients presenting with a primary or secondary diagnosis of HF to Central Australia's Alice Springs Hospital during 2008-2012 was performed. The population rate of admission and subsequent outcomes (including mortality and readmission) during the 5-year study period were examined. A total of 617 patients, aged 55.8 ± 17.5 years and 302 (49%) female constituted the study cohort. The 446 Indigenous patients (72%) were significantly younger (50.8 ± 15.9 vs 68.7 ± 14.9; P < .001) and clinically more complex compared with the non-Indigenous patients. Annual prevalence of any HF hospitalization was markedly higher in the Indigenous population (1.9%, 95% CI 1.7-2.1) compared with the non-Indigenous population (0.5%, 95% CI 0.4-0.6); the greatest difference being for women. Overall, non-Indigenous patients had poorer outcomes and were significantly more likely to die (P < .0001), but this was largely driven by age differences. Alternatively, Indigenous patients were significantly more likely to have a higher number of hospitalizations, although indigeneity was not a predictor for 30- or 365-day rehospitalization from the index admission. CONCLUSION: The pattern of HF among Indigenous Australians in Central Australia is characterized by a younger population with more clinically complex cases and greater health care utilization.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2016: the Influenza Complications Alert Network (FluCAN).

During the period 1 April to 30 October 2016 (the 2016 influenza season), 1,952 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 46% were elderly (e65 years), 18% were children (<16 years), 5% were Aboriginal and Torres Strait Islander peoples, 3% were pregnant and 76% had chronic co-morbidities.

HIV Risk, Substance Use, and Personality Characteristics among Adults with History of Serious Mental Illness.

The present study examined the relationship between characteristics associated with personality disorders, substance use, and HIV risk among adults with a history of serious mental illness. Participants included 103 adults with antisocial or borderline personality disorder, serious mental illness, and recent HIV risk behavior. The sample was predominately male (64%), diverse (42% African American and 13% Hispanic), and homeless/marginally housed (76%). In order to examine the relationship between personality characteristics and risk we constructed a risk index comprising key symptoms of antisocial and borderline personality disorders, namely; impulsivity, affective instability, and disregard for safety of self/others. Contrary to our primary hypotheses, risk index scores did not predict HIV risk behavior and substance abuse did not mediate this risk. Exploratory analyses did reveal that women engaged in significantly more risk behaviors than their male counterparts and that risk scores were a significant predictor of total sex acts for women but not men. In addition, increased emotional dysregulation was a significant predictor of condomless sex acts for women but not men. Finally, recent alcohol use and increased impulsivity was associated with more condomless oral sex for men and women. These results suggest the relationship among serious mental illness, personality disorder, substance abuse, and gender is complex and merits further study.

The epidemiology of gonococcal arthritis in an Indigenous Australian population.

BACKGROUND: Disseminated Gonococcal Infection (DGI) is caused by Neisseria gonorrhoeae bacteraemia. Typically the primary source is a sexually acquired mucosal infection. If not recognised and treated promptly DGI can be associated with significant morbidity and, in rare cases, death. Central Australia has one of the highest rates of gonococcal notifications in Australia. Despite this, the nature and prevalence of complications arising from gonococcal infections within this at-risk population is unknown. METHODS: Enhanced surveillance and audit of patients with DGI discharged from Alice Springs Hospital between 2003 and 2012. Patient demographics and clinical management data were extracted from healthcare records and investigation databases. RESULTS: DGI cases were significantly more likely to present in young (≤29 years) Indigenous women compared with young Indigenous men (χ(2), p=0.020). Overall Indigenous women had nearly twice the risk of DGI compared with men (relative risk 1.92 (95% CI 1.45 to 2.53)). The incidence of DGI per all gonococcal notifications on average was 911/100 000 (95% CI 717 to 1142) gonococcal notifications. CONCLUSIONS: DGI represents a severe complication of N. gonorrhoeae infection. In Central Australia DGI is not a rare oddity but rather an important differential when dealing with patients with undefined sepsis and associated joint disease.

Autoimmune rheumatic disease in Australian Aboriginal and Torres Strait Islander Peoples: What do we know?

Autoimmune rheumatic disease (AIRD) is a collective term, which comprises a group of multisystem inflammatory autoimmune diseases, including connective tissue disease, chronic inflammatory arthritis, sarcoidosis and systemic vasculitis. Some AIRD are prevalent in the general population, and all can cause significant morbidity and reduced quality of life, with some increasing the risk of premature mortality, such as systemic lupus erythematosus (SLE), a connective tissue disease that is more prevalent and severe in Australian Aboriginal and Torres Strait Islander Peoples with high mortality rates. To ensure that management of AIRD can be optimised for all Australians, it is important that we understand the prevalence and potential phenotypic variations of AIRD across the Australian population. However, to date there have been few described cases of AIRD other than SLE in Aboriginal and Torres Strait Islander Peoples. In this review, we summarise what is known about AIRD other than SLE in Aboriginal and Torres Strait Islander Peoples, particularly with regards to prevalence, phenotype and disease outcomes, and highlight the current gaps in knowledge.

Systemic lupus erythematosus in Aboriginal and Torres Strait Islander peoples in Australia: addressing disparities and barriers to optimising patient care.

The first inhabitants of Australia and the traditional owners of Australian lands are the Aboriginal and Torres Strait Islander peoples. Aboriginal and Torres Strait Islander peoples are two to four times more likely to have systemic lupus erythematosus (SLE) than the general Australian population. Phenotypically, SLE appears distinctive in Aboriginal and Torres Strait Islander peoples and its severity is substantially increased, with mortality rates up to six times higher than in the general Australian population with SLE. In particular, Aboriginal and Torres Strait Islander peoples with SLE have increased prevalence of lupus nephritis and increased rates of progression to end-stage kidney disease. The reasons for the increased prevalence and severity of SLE in this population are unclear, but socioeconomic, environmental, and biological factors are all likely to be implicated, although there are no published studies investigating these factors in Aboriginal and Torres Strait Islander peoples with SLE specifically, indicating an important knowledge gap. In this Review, we summarise the data on the incidence, prevalence, and clinical and biological findings relating to SLE in Aboriginal and Torres Strait Islander peoples and explore potential factors contributing to its increased prevalence and severity in this population. Importantly, we identify health disparities and deficiencies in health-care provision that limit optimal care and outcomes for many Aboriginal and Torres Strait Islander peoples with SLE and highlight potentially addressable goals to improve outcomes.

Stroke incidence and subtypes in Aboriginal people in remote Australia: a healthcare network population-based study.

OBJECTIVES: We aimed to compare the incidence, subtypes and aetiology of stroke, and in-hospital death due to stroke, between Aboriginal and non-Aboriginal people in Central Australia, a remote region of Australia where a high proportion Aboriginal people reside (40% of the population). We hypothesised that the rates of stroke, particularly in younger adults, would be greater in the Aboriginal population, compared with the non-Aboriginal population; we aimed to elucidate causes for any identified disparities. DESIGN: A retrospective population-based study of patients hospitalised with stroke within a defined region from 1 January 2011 to 31 December 2014. SETTING: Alice Springs Hospital, the only neuroimaging-capable acute hospital in Central Australia, serving a network of 50 healthcare facilities covering 672 000 km2. PARTICIPANTS: 161 residents (63.4% Aboriginal) of the catchment area admitted to hospital with stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of first-ever stroke, overall (all events) stroke and in-hospital death. RESULTS: Of 121 residents with first-ever stroke, 61% identified as Aboriginal. Median onset-age (54 years) was 17 years younger in Aboriginal patients (p<0.001), and age-standardised stroke incidence was threefold that of non-Aboriginal patients (153 vs 51 per 100 000, incidence rate ratio 3.0, 95% CI 2 to 4). The rate ratios for the overall rate of stroke (first-ever and recurrent) were similar. In Aboriginal patients aged <55 years, the incidence of ischaemic stroke was 14-fold greater (95% CI 4 to 45), and intracerebral haemorrhage 19-fold greater (95% CI 3 to 142) than in non-Aboriginal patients. Crude prevalence of diabetes mellitus (70.3% vs 34.0%, p<0.001) and hypercholesterolaemia (68.9% vs 51.1%, p=0.049) was greater, and age-standardised in-hospital deaths were fivefold greater (35 vs 7 per 100 000, 95% CI 2 to 11) in Aboriginal patients than in non-Aboriginal patients. CONCLUSIONS: Stroke incidence (both subtypes) and in-hospital deaths for remote Aboriginal Australians are dramatically greater than in non-Aboriginal people, especially in patients aged <55 years.

Gender and other psychosocial factors as predictors of adherence to highly active antiretroviral therapy (HAART) in adults with comorbid HIV/AIDS, psychiatric and substance-related disorder.

This study assessed adherence to HAART among 67 HIV-infected adults, and the degree to which gender and psychological factors-including depression, drug and alcohol use, quality of life, and medication side effects-influenced adherence. Although overall adherence was greater than rates reported in similar studies, no significant difference in adherence was observed between men and women in the present sample. Medication side effects were a significant predictor of non-adherence in the sample at large and among women in particular, while alcohol dependence was a significant predictor of non-adherence only in women. Possible explanations are explored.

Bronchiectasis in Central Australia: a young face to an old disease.

BACKGROUND: Bronchiectasis remains a significant cause of morbidity among specific populations world wide, including many indigenous groups. Data on prevalence in Australian adults are lacking. Indigenous children in Central Australia have the highest rates of bronchiectasis in the world. Outcomes for these individuals after they become adults are not currently available. METHODS: We performed a retrospective case review of the presentation and likely aetiology of adult patients presenting to the Alice Springs Hospital with a primary diagnosis of bronchiectasis. RESULTS: Sixty-one patients and 166 admissions were identified. Fifty-nine patients were indigenous (97%). Mean age was 42+/-15 years. Forty-three patients (70%) had past histories notable for recurrent respiratory tract infections. No predisposing factors could be identified in 11 patients (18%). Human T-cell lymphotropic virus type 1 (HTLV-1) serology was positive in 72% of those studied. Eight (13%) patients died during the study period. CONCLUSION: Bronchiectasis remains a significant cause of morbidity and mortality in Central Australia, with notably different patient characteristics and disease aetiology to other published cohorts. Recurrent respiratory infection is the major cause of illness. Associated factors include indigenous ethnicity, HTLV-1 positivity and childhood in a remote region.

Depressive symptoms and risk of stroke: the Framingham Study.

BACKGROUND AND PURPOSE: Emerging evidence raises the possibility of an association between depression and stroke risk. This study sought to examine whether depressive symptoms are associated with an increased risk of cerebrovascular events in a community-based sample. METHODS: A prospective study was conducted on 4120 Framingham Heart Study participants aged 29 to 100 years with up to 8 years of follow-up. The Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms. Incident stroke and transient ischemic attack (TIA) events were assessed by uniform diagnostic criteria. The association between depressive symptoms and risk of stroke/TIA was analyzed with Cox proportional-hazards models, after adjusting for traditional stroke risk factors. RESULTS: In participants <65 years, the risk of developing stroke/TIA was 4.21 times greater (P= <0.001) in those with symptoms of depression. After adjusting for components of the Framingham Stroke Risk Profile (hazard ratio=3.43, 95% CI=1.60 to 7.36, P=0.002) and education (hazard ratio=4.89, 95% CI=2.19 to 10.95), similar results were obtained. In subjects aged 65 and older, depressive symptoms were not associated with an increased risk of stroke/TIA. Taking antidepressant medications did not alter the risk associated with depressive symptoms. CONCLUSIONS: In this community-based study, depressive symptoms were an independent risk factor for incident stroke/TIA in individuals <65 years. These data suggest that identification of depressive symptoms at younger ages may have an impact on the primary prevention of stroke.

Cutaneous polyarteritis nodosa in children.

The purpose of this study was to present the clinical courses and histologic findings of 4 children with cutaneous vasculitis characterized by tender cutaneous nodules and fever in the absence of major organ involvement. We conducted a retrospective chart review of 4 patients with cutaneous vasculitis followed up for a mean of 68 months (range, 12-114 months). The patients included 3 boys and 1 girl (ages at onset, 2-10 years). Clinical and laboratory manifestations included tender erythematous cutaneous nodules (n = 4/4), fever 39 degrees C or higher (4/4), nondeforming arthritis (3/4), leukocytosis and elevated erythrocyte sedimentation rate (4/4), positive antinuclear antibodies (1/4), and elevated streptococcal enzymes (3/4). Skin biopsy results showed inflammation of medium-sized cutaneous arteries with a mixed inflammatory cell infiltrate consistent with cutaneous polyarteritis nodosa (4/4). Patients were treated with prednisone with good initial response, but exacerbation occurred once prednisone was tapered. Additional medications given were methotrexate (2/4), dapsone (2/4), colchicine (1/4), and cyclophosphamide (1/4). One patient is in clinical remission after 48 months of disease; the others have continuing disease that requires treatment. Patients with evidence of streptococcal infection received oral penicillin prophylaxis; two of the three patients had recurrent attacks of vasculitis despite penicillin. No patients have developed major organ system involvement after 12 to 114 months of follow-up. Cutaneous polyarteritis nodosa in children is a recognizable entity characterized by painful nodules, fever, absence of major organ involvement, and chronic or recurrent course. Patients should be screened for streptococcal infection and treated with antibiotics when needed.

A prostate-specific antigen (PSA)-activated vinblastine prodrug selectively kills PSA-secreting cells in vivo.

Currently, there is no therapy for men with androgen-refractory prostate cancer that substantially extends survival. This report characterizes by in vitro and in vivo techniques a new chemotherapeutic that is composed of desacetyl-vinblastine covalently linked to a peptide that contains a peptide bond that can be hydrolyzed by prostate-specific antigen (PSA). This compound (referred to as vinblastine-conjugate) is minimally toxic to cells in culture which do not express PSA. In the presence of PSA, the peptide moiety is hydrolyzed, generating several highly toxic metabolites that contain vinblastine. Animals bearing PSA-positive human prostate tumors that were treated with the vinblastine-conjugate experienced a >99% reduction in PSA serum level. In contrast, animals bearing PSA-positive human prostate tumors treated with the cytotoxic metabolites derived from the PSA hydrolysis of the vinblastine-conjugate showed a nonsignificant change in both PSA and tumor weight values. The cell killing activity of the vinblastine-conjugate is PSA dependent because animals bearing non-PSA-producing human tumor xenografts had a nonsignificant increase in tumor weight after vinblastine-conjugate treatment. Exploratory efficacy/toxicity studies in LNCaP tumor-bearing nude mice were conducted with animals treated for 5 consecutive days with various doses of either the vinblastine-conjugate or a PSA-generated toxic metabolite (desacetyl-vinblastine). The desacetyl-vinblastine treatment resulted in 10-70% mortality with a very slight effect on tumor growth. In contrast, vinblastine-conjugate treatments resulted in no mortality, good to excellent antitumor efficacy, very slight to slight peripheral neuropathy and myelopathy, and slight to severe testicular degeneration. Similar treatment of beagle dogs with the vinblastine-conjugate showed even less toxicity. These data support the use of the PSA-hydrolyzable vinblastine-conjugate as an experimental therapy for prostate cancer in man.

Design and synthesis of a pro-drug of vinblastine targeted at treatment of prostate cancer with enhanced efficacy and reduced systemic toxicity.

Chemotherapy of prostate cancer with antimitotic agents such as vinblastine and doxorubicin is only marginally effective, due to dose-limiting systemic toxicity. Herein we report the development of peptidyl conjugate 5 of the cytotoxic agent vinblastine (1), along with the results of its in vitro and in vivo evaluation as a pro-drug targeted at prostate cancer cells. Prostate-derived tumors are known to produce significant amounts of prostate specific antigen (PSA), a serine protease with chymotrypsin-like properties. Earlier work in these laboratories established that an appropriately engineered peptidyl pro-drug will release active cytotoxic agent strictly within the microenvironment of the tumor tissue (Garsky, V. M., et al. J. Med.Chem. 2001, 44, 4216-4224). Conjugate 5, which features an octapeptide segment attached by an ester linkage at the 4-position of vinblastine (1), undergoes rapid cleavage by PSA (T(1/2) = 12 min) between the Gln and Ser residues. In nude mouse xenograft studies, 5 reduced circulating PSA levels by 99% and tumor weight by 85% at a dose just below its MTD. By contrast, the putative end-point metabolite, the cytotoxic agent des-acetyl vinblastine (1b), was ineffective in reducing PSA levels and tumor burden at its maximum tolerated doses. Additional data from metabolism studies on 5 support the supervention of a novel in vivo processing mechanism, the spontaneous release of 1b from a dipeptidyl intermediate driven by favorable diketopiperazine formation.

Physical and sexual abuse in the lives of HIV-positive women enrolled in a primary medicine health maintenance organization.

Over the past several years, the proportion of all cases of AIDS in the United States among adult and adolescent women has more than tripled from 7% in 1985 to 23% in 1998. Information obtained in the present study suggests that care providers need to be aware of the unique life circumstances of women with AIDS, which may predispose them to a number of negative health and mental health outcomes. Charts of the first 100 women enrolled in an intensive home-based primary medical HMO for people with advanced HIV/AIDS were examined retrospectively for evidence of trauma. Results from a chart review and nursing care assessments of these patients revealed that women with HIV/AIDS were significantly more likely to have had traumatic life experiences compared to the larger population [as measured in a National Comorbidity Survey (NCS)]. In this study, one-half of the patients reported a lifetime history of sexual assault compared to 9% of the general population, one-third reported a history of incest compared to 12% in the NCS, and 83% reported significant physical abuse compared to 4% in the NCS. Such traumatic life experiences are frequently associated with high rates of psychiatric comorbidity, substance abuse, and possible nonadherence to health care. Providers of AIDS care need to be aware of the complex mental health and psychosocial needs of traumatized women with AIDS and make better use of collateral mental health providers and consultation. The ways in which this particular sample of women may be nonrepresentative of women living with AIDS, in general, including the observation that they may be a particularly traumatized and challenging cohort, and other limitations of the data, including the methods used for chart review, are discussed.

Influenza vaccine effectiveness against hospitalisation with confirmed influenza in the 2010-11 seasons: a test-negative observational study.

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.