Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

Background: Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4 + count). Methods: We used fresh blood from HIV-positive and at-risk HIVnegative women, with and without chronic HCV, to measure percentages of activated CD4 + and CD8 + T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic. Results: In multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4 + (P = 0.03), 33% more EM CD4 + (P = 0.0002), and 37% fewer central memory CD8 + (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4 + among HCV viremic women. Furthermore, the association with EM CD4 + among HIV positives was limited to individuals with diminished immune status (total CD4 + count #500 cells/mL), as were associations of HCV viremia with higher percentages of activated CD4 + and Tregs. Among HIV positives with high CD4 + count, no significant associations were observed. Conclusions: These data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4 + count

Non-communicable disease mortality in young people with a history of contact with the youth justice system in Queensland, Australia: a retrospective, population-based cohort study

Summary: Background: Young people who have had contact with the criminal justice system are at increased risk of early death, especially from injuries. However, deaths due to non-communicable diseases (NCDs) in this population remain poorly described. We aimed to estimate mortality due to NCDs in people with a history of involvement with the youth justice system, compare NCD mortality rates in this population with those in the general population, and characterise demographic and justice-related factors associated with deaths caused by NCDs in people with a history of contact with the youth justice system. Methods: In this retrospective, population-based cohort study (the Youth Justice Mortality [YJ-Mort] study), we included all people aged 10–18 years (at baseline) charged with a criminal offence in Queensland, Australia, between June 30, 1993, and July 1, 2014. We probabilistically linked youth justice records with adult correctional records and national death records up to Jan 31, 2017. Indigenous status was ascertained from youth justice and adult correctional records, with individuals identified as Indigenous in either source classified as Indigenous in the final dataset. We estimated crude mortality rates and standardised mortality ratios (SMRs) for comparisons with data from the Australian general population. We identified risk factors for NCD deaths using competing-risks regression. Findings: Of 48 670 individuals aged 10–18 years (at baseline) charged with a criminal offence in Queensland, Australia, between June 30, 1993, and July 1, 2014, 11 897 (24·4%) individuals were female, 36 773 (75·6%) were male, and 13 250 (27·2%) were identified as identified as Indigenous. The median age at first contact with the youth justice system was 15 years (IQR 14–16), the median follow-up time was 13·4 years (8·4–18·4), and the median age at the end of the study was 28·6 years (23·6–33·6). Of 1431 deaths, 932 (65·1%) had a known and attributed cause, and 121 (13·0%) of these were caused by an NCD. The crude mortality rate from NCDs was 18·5 (95% CI 15·5–22·1) per 100 000 person-years among individuals with a history of involvement with the youth justice system, which was higher than among the age-matched and sex-matched Australian general population (SMR 1·67 [1·39–1·99]). Two or more admissions to adult custody (compared with none; adjusted sub-distribution hazard ratio 2·09 [1·36–3·22]), and up to 52 weeks in adult custody (compared with none; 1·98 [1·18–3·32]) was associated with NCD death. Interpretation: Young people with a history of contact with the justice system are at increased risk of death from NCDs compared with age-matched and sex-matched peers in the general Australian population. Reducing youth incarceration and providing young people's rights to access clinical, preventive, and restorative services should be a priority. Funding: National Health and Medical Research Council

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors

Background: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. Methods: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. Findings: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m3). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74–2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28–16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. Interpretation: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. Funding: None