Electron Capture vs Transfer Dissociation for Site Determination of Tryptic Peptide Tyrosine Sulfation: Direct Detection of Fibrinogen Sulfation Sites and Identification of Novel Isobaric Interferences.

Tyrosine sulfation, an understudied but crucial post-translational modification, cannot be directly detected in conventional nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) due to the extreme sulfate lability. Here, we report the detection of sulfate-retaining fragments from LC-electron capture dissociation (ECD) and nanoLC-electron transfer higher energy collision dissociation (EThcD). Sulfopeptide candidates were identified by Proteome Discoverer and MSFragger analysis of nanoLC-HCD MS/MS data and added to inclusion lists for LC-ECD or nanoLC-EThcD MS/MS. When this approach failed, targeted LC-ECD with fixed m/z isolation windows was performed. For the plasma protein fibrinogen, the known pyroglutamylated sulfopeptide QFPTDYDEGQDDRPK from the beta chain N-terminus was identified despite a complete lack of sulfate-containing fragment ions. The peptide QVGVEHHVEIEYD from the gamma-B chain C-terminus was also identified as sulfated or phosphorylated. This sulfopeptide is not annotated in Uniprot but was previously reported. MSFragger further identified a cysteine-containing peptide from the middle of the gamma chain as sulfated and deamidated. NanoLC-EThcD and LC-ECD MS/MS confirmed the two former sulfopeptides via sulfate-retaining fragment ions, whereas an unexpected fragmentation pattern was observed for the third sulfopeptide candidate. Manual interpretation of the LC-ECD spectrum revealed two additional isobaric identifications: a trisulfide-linked cysteinyl-glycine or a carbamidomethyl-dithiothreiotol covalent adduct. Synthesis of such adducts confirmed the latter identity.

Primary health care service utilisation before and after entry into long-term care in Australia.

OBJECTIVES: To examine utilisation of primary health care services (subsidised by the Australian Government, Medicare Benefits Schedule, MBS) before and after entry into long-term care (LTC) in Australia. METHODS: A retrospective cohort study of older people (aged ≥65 years) who entered LTC in Australia between 2012 and 2016 using the Historical Cohort of the Registry of Senior Australians. MBS-subsidised general attendances (general practitioner (GP), medical and nurse practitioners), health assessment and management plans, allied health, mental health services and selected specialist attendances accessed in 91-day periods 12 months before and after LTC entry were examined. Adjusted relative changes in utilisation 0-3 months before and after LTC entry were estimated using risk ratios (RR) calculated using Generalised Estimating Equation Poisson models. RESULTS: 235,217 residents were included in the study with a median age of 84 years (interquartile range 79-89) and 61.1% female. In the first 3 months following LTC entry, GP / medical practitioner attendances increased from 86.6% to 95.6% (aRR 1.10 95%CI 1.10-1.11), GP / medical practitioner urgent after hours (from 12.3% to 21.1%; aRR 1.72, 95%CI 1.70-1.74) and after-hours attendances (from 18.5% to 33.8%; aRR 1.83, 95%CI 1.81-1.84) increased almost two-fold. Pain, palliative and geriatric specialist medicine attendances were low in the 3 months prior (<3%) and decreased further following LTC admission. CONCLUSION: There is an opportunity to improve the utilisation of primary health care services following LTC entry to ensure that residents' increasingly complex care needs are adequately met.

Primary, allied health, geriatric, pain and palliative healthcare service utilisation by aged care residents, 2012-2017.

OBJECTIVES: To examine the incidence and trends in primary care, allied health, geriatric, pain and palliative care service use by permanent residential aged care (PRAC) residents and the older Australian population. METHODS: Repeated cross-sectional analyses on PRAC residents (N = 318,484) and the older (≥65 years) Australian population (N ~ 3.5 million). Outcomes were Medicare Benefits Schedule (MBS) subsidised primary care, allied health, geriatric, pain and palliative services between 2012-13 and 2016-17. GEE Poisson models estimated incidence rates and incidence rate ratios (IRR). RESULTS: In 2016-17, PRAC residents had a median of 13 (interquartile range [IQR] 5-19) regular general medical practitioner (GP) attendances, 3 (IQR 1-6) after-hours attendances and 5% saw a geriatrician. Highlights of utilisation changes from 2012-13 to 2016-17 include the following: GP attendances increased by 5%/year (IRR = 1.05, 95% confidence interval [CI] 1.05-1.05) for residents compared to 1%/year (IRR = 1.01, 95%CI 1.01-1.01) for the general population. GP after-hours attendances increased by 15%/year (IRR = 1.15, 95%CI 1.14-1.15) for residents and 9%/year (IRR = 1.08, 95%CI 1.07-1.20) for the general population. GP management plans increased by 12%/year (IRR = 1.12, 95%CI 1.11-1.12) for residents and 10%/year (IRR = 1.10, 95%CI 1.09-1.11) for the general population. Geriatrician consultations increased by 28%/year (IRR = 1.28, 95%CI 1.27-1.29) for residents compared to 14%/year (IRR = 1.14, 95%CI 1.14-1.15) in the general population. CONCLUSIONS: The utilisation of most examined services increased in both cohorts over time. Preventive and management care, by primary care and allied health care providers, was low and likely influences the utilisation of other attendances. PRAC residents' access to pain, palliative and geriatric medicine services is low and may not address the residents' needs.

Trends in mental health service utilisation by Australia's older population.

OBJECTIVES: To examine the incidence, trends, and differences between age groups and sex in Medicare Benefits Schedule (MBS)-subsidised mental health service utilisation by older Australians over the past 10 years. METHODS: A cross-sectional cohort study between 1 July 2009 and 30 June 2019 was conducted using publicly available MBS data for older individuals aged ≥65 years. Age- and sex-standardised yearly incidence rates of psychological therapy (MBS M06), GP mental health treatments (MBS A20), focussed psychological strategy (MBS M07), and psychiatric attendances (MBS A08) and incidence rate ratios (IRR) estimated using Poisson regression were calculated. RESULTS: Overall, the rate of utilisation of primary care mental health services by the older population increased over the study period, with psychological therapy claims increasing the greatest from 14.4/1000 older persons in 2009/10 to 38.5/1000 in 2018/19 (IRR 1.11, 95% CI 1.09-1.13), followed by GP mental health treatments increasing from 43.7/1000 (95% CI 43.4-43.9) in 2009/10 to 81.0/1000 (95% CI 80.7-81.3) in 2018/19 (IRR 1.07/year, 95% CI 1.06-1.09). Females aged 65-74 years had the highest use of GP mental health treatments at 123.8/1000 compared to 63.6/1000 in males in 2018/2019. CONCLUSIONS: While utilisation of mental health services by the older population in Australia has increased over the study period, it is important that policymakers and service providers continue to support access and use of these services, which may facilitate well-being and quality of life in the older population.

Government-subsidised mental health services are underused in Australian residential aged care facilities.

Objective To describe patterns of use of the available Government-subsidised mental health services among people living in Australian residential aged care facilities. Methods A retrospective population-based trend analysis was conducted, including all non-Indigenous people living in an Australian facility between 2012 and 2017. Adjusted incidence proportions and trends were estimated for four groups of mental health services. Results The use of Medicare-subsidised mental health services was very low overall. The proportion of residents who accessed primary care mental health services increased from 1.3% in 2012/2013 to 2.4% in 2016/2017, while psychiatry service use increased from 1.9 to 2.3%. Claims for clinical psychology increased from 0.18 to 0.26%, and claims for a registered psychologist, occupational therapist or social worker rose from 0.45 to 1.2%. People with dementia were less likely than people without dementia to access all services aside from psychiatry services. Conclusions Less than 3% of residents accessed funding subsidies for mental health services and people with dementia experienced pronounced barriers to service access. Mental health care is a pillar of the publicly-funded health system in Australia, and low use of these services among aged care residents indicates a need for organisational and policy changes to improve access.

National Trends and Policy Impacts on Provision of Home Medicines Reviews and Residential Medication Management Reviews in Older Australians, 2009-2019.

Comprehensive medicines reviews such as Home Medicines Review (HMR) and Residential Medication Management Review (RMMR) can resolve medicines-related problems. Changes to Australia's longstanding HMR and RMMR programs were implemented between 2011 and 2014. This study examined trends in HMR and RMMR provision among older Australians during 2009-2019 and determined the impact of program changes on service provision. Monthly rates of general medical practitioner (GP) HMR claims per 1000 people aged ≥65 years and RMMR claims per 1000 older residents of aged care facilities were determined using publicly available data. Interrupted time series analysis was conducted to examine changes coinciding with dates of program changes. In January 2009, monthly HMR and RMMR rates were 0.80/1000 older people and 20.17/1000 older residents, respectively. Small monthly increases occurred thereafter, with 1.89 HMRs/1000 and 34.73 RMMRs/1000 provided in February 2014. In March 2014, immediate decreases of -0.32 (95%CI -0.52 to -0.11) HMRs/1000 and -12.80 (95%CI -15.22 to -10.37) RMMRs/1000 were observed. There were 1.07 HMRs/1000 and 35.36 RMMRs/1000 provided in December 2019. In conclusion, HMR and RMMR program changes in March 2014 restricted access to subsidized medicines reviews and were associated with marked decreases in service provision. The low levels of HMR and RMMR provision observed do not represent a proactive approach to medicines safety and effectiveness among older Australians.

Basic epidemiology of wellbeing among children and adolescents: A cross-sectional population level study.

Wellbeing and mental health are fundamental rights of children and adolescents essential for sustainable development. Understanding the epidemiology of child and adolescent wellbeing is essential to informing population health approaches to improving wellbeing and preventing mental illness. The present study estimated the prevalence of wellbeing and how wellbeing indicators were distributed across social and economic groups. This study used data from the 2019 Wellbeing and Engagement Collection; an annual census conducted in South Australian schools that measures self-reported wellbeing in students aged 8-18 years (n = 75,966). We estimated the prevalence (n, %) of low, medium and high wellbeing across five outcomes: life satisfaction, optimism, sadness, worries and happiness, overall and stratified by gender, age, language background, socio-economic position and geographical remoteness. The prevalence of low wellbeing on each indicator was: happiness 13%, optimism 16%, life satisfaction 22%, sadness 16% and worries 25%. The prevalence of low wellbeing increased with age, particularly for females. For example, 22.5% of females aged 8-10 years had high levels of worries compared to 43.6% of 15 to 18-year old females. Socioeconomic inequality in wellbeing was evident on all indicators, with 19.5% of children in the most disadvantaged communities having high levels of sadness compared to 12.5% of children in the most advantaged communities. Many children and adolescents experience low wellbeing on one or more indicators (40.7%). The scale of this problem warrants a population-level preventative health response, in addition to a clinical, individual-level responses to acute mental health needs. Universal school-based programs that support social and emotional wellbeing have a role to play in this response but need to be supported by universal and targeted responses from outside of the education system.

Inequalities in child development at school entry: A repeated cross-sectional analysis of the Australian Early Development Census 2009-2018.

BACKGROUND: Australia is the only developed country to consistently undertake a developmental census of its children nationwide. The repeated collection of the Australian Early Development Census (AEDC) has provided an unprecedented opportunity to examine the prevalence of developmental vulnerability across Australia's states and territories, the socio-economic distribution of developmental vulnerability across jurisdictions, and how these distributions might have changed over time. METHODS: This study employed multivariable logistic regressions to estimate the probability of developmental vulnerability within each jurisdiction and AEDC collection year (2009 to 2018), adjusting for jurisdictional differences in socio-demographic characteristics. To explore socio-economic inequalities in child development, adjusted slope index of inequality (SII) models were utilised. FINDINGS: The results of this study found reductions in the adjusted prevalence of developmental vulnerability over time in Western Australia (26% to 20%) and Queensland (30% to 25%), with an increase observed in the Australian Capital Territory (27% to 30%). Analysis also indicated an increase in socio-economic inequalities over time in the Northern Territory (+12%), the Australian Capital Territory (+6%) and Tasmania (+4%). Sensitivity analysis found these effects to be robust with an alternative measure of socio-economic position. INTERPRETATION: There is considerable variation in the prevalence and socio-economic inequalities in developmental vulnerability across Australia's jurisdictions. Future research should explore the policy drivers in early childhood education and health contributing to the findings of this study, with a particular focus on jurisdictions where there have been notable changes in developmental vulnerability and socio-economic inequality over time. FUNDING: Analyses were funded under research contract by the Department of Education, Skills and Employment. Prof Brinkman is supported by a National Health and Medical Research Council fellowship, APP1160185.