Legal capacity, developmental capacity, and impaired mental capacity in children under 16: Neurodevelopment and the law in Northern Ireland.

When people of any age, despite all possible support being provided, are unable to make a necessary decision, then it is important to have a legal framework which promotes and protects their rights. There is ongoing debate about how this can be achieved, in a non-discriminatory way, for adults but it is also an important consideration for children and young people. In Northern Ireland, the Mental Capacity Act (Northern Ireland) 2016, when fully implemented will provide a non-discriminatory framework for those aged 16 and over. Arguably this addresses discrimination based on disability but continues to discriminate based on age. This article explores some of the possible ways the rights of those aged under 16 could be further promoted and protected. These approaches may include: retaining the current combination of statute law but developing new guidance to inform practice for those aged under 16; codifying Gillick to clarify under what circumstances those aged under 16 can accept, and possibly also refuse, interventions; amend the Children (Northern Ireland) Order 1995 to provide a more comprehensive framework for health and welfare decision making; amend and extend the Mental Capacity Act (Northern Ireland) 2016 to apply to those aged under 16; or develop a new law specifically focused on the emerging capacity of those aged under 16. There are complex issues involved including how to consider emerging or developmental decision-making ability, and the role of those with parental responsibility, but the complexities involved should not prevent these issues being addressed.

Linking Australian Stroke Clinical Registry data with Australian government Medicare and medication dispensing claims data and the potential for bias.

OBJECTIVE: We aim to report the accuracy of linking data from a non-government-held clinical quality registry to national claims data and identify associated sources of systematic bias. METHODS: Patients with stroke or transient ischaemic attack admitted to hospitals participating in the Australian Stroke Clinical Registry (AuSCR) were linked with Medicare and medication dispensings through the Australian Medicare enrolment file (MEF). The proportion of registrants in the datasets was calculated and factors associated with a non-merge assessed using multivariable analyses. RESULTS: A total of 17,980 AuSCR registrants (January 2010 - July 2014) were submitted for linkage (median age 76 years; 46% female; 67% ischaemic stroke); the proportion merged was 97% MEF, 93% Medicare and 95% medication dispensings. Data from registrants born in Asia were less likely to link with the MEF (adjusted Odds Ratio [aOR]: 0.20; 95%Confidence Interval [CI]: 0.15, 0.27). Data for those aged 85-plus compared to those under 65 years were less likely to merge with Medicare (aOR 0.25; 95%CI:0.21, 0.30) but more likely to merge with dispensing claims data (aOR: 2.15 (95%CI:1.71, 2.69). Implications for public health: Linkage between the AuSCR, a national clinical quality registry and Commonwealth datasets was achieved and potential sources of bias were identified.

Evaluating recruitment strategies for AUSPICE, a large Australian community-based randomised controlled trial.

OBJECTIVES: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). DESIGN, SETTING, PARTICIPANTS: Men and women aged 55-60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. METHODS: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55-60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. MAIN OUTCOME: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. RESULTS: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. CONCLUSIONS: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

Maximising data value and avoiding data waste: a validation study in stroke research.

OBJECTIVES: To determine the feasibility of linking data from the Australian Stroke Clinical Registry (AuSCR), the National Death Index (NDI), and state-managed databases for hospital admissions and emergency presentations; to evaluate data completeness and concordance between datasets for common variables. DESIGN, SETTING, PARTICIPANTS: Cohort design; probabilistic/deterministic data linkage of merged records for patients treated in hospital for stroke or transient ischaemic attack from New South Wales, Queensland, Victoria, and Western Australia. MAIN OUTCOME MEASURES: Descriptive statistics for data matching success; concordance of demographic variables common to linked databases; sensitivity and specificity of AuSCR in-hospital death data for predicting NDI registrations. RESULTS: Data for 16 214 patients registered in the AuSCR during 2009-2013 were linked with one or more state datasets: 15 482 matches (95%) with hospital admissions data, and 12 902 matches (80%) with emergency department presentations data were made. Concordance of AuSCR and hospital admissions data exceeded 99% for sex, age, in-hospital death (each κ = 0.99), and Indigenous status (κ = 0.83). Of 1498 registrants identified in the AuSCR as dying in hospital, 1440 (96%) were also recorded by the NDI as dying in hospital. In-hospital death in AuSCR data had 98.7% sensitivity and 99.6% specificity for predicting in-hospital death in the NDI. CONCLUSION: We report the first linkage of data from an Australian national clinical quality disease registry with routinely collected data from several national and state government health datasets. Data linkage enriches the clinical registry dataset and provides additional information beyond that for the acute care setting and quality of life at follow-up, allowing clinical outcomes for people with stroke (mortality and hospital contacts) to be more comprehensively assessed.

Mechanisms of the immune response cause by cationic and anionic surface functionalized cellulose nanocrystals using cell-based assays.

The interest in functionalized cellulose nanocrystals (CNCs) for multiple biomedical application has been increasing in recent years. CNCs are suitable to functionalization with an array of polymers, generating chemically related nanomaterials with different morphologies, surface charges that can affect bioreactivity, including immune response. In this study, we sought to understand the mechanistic differences regarding immunological responses evoked by functionalized CNCs and whether surface charges play a role in this effect. We investigated the effect of a cationic, CNCs-poly(APMA), and an anionic, CNCs-poly(NIPAAm) derivatives on the secretion of inflammatory cytokines, mitochondria-derived ROS and mitochondrial function and antioxidant response as well as on endoplasmic reticulum (ER) stress, in human and murine inflammatory cells. The cationic CNCs-poly(APMA) evoked a more robust immunological response in murine cell line, while the anionic CNCs-poly(NIPAAm) showed a significant NLRP3 inflammasome-dependent and independent immunological response in human monocytes. Moreover, CNCs-poly(NIPAAm) induced greater formation of acidic vesicular organelles, mitochondrial ROS in non-stimulated cells while CNCs-poly(APMA) mainly affected mitochondrial function by decreasing the intracellular ATP. The differences on the biological responses may be related to the surface charges of CNCs, and their likely interactions with intra and extracellular biomolecules.

Addressing the challenges of cross-jurisdictional data linkage between a national clinical quality registry and government-held health data.

OBJECTIVE: To describe the challenges of obtaining state and nationally held data for linkage to a non-government national clinical registry. METHODS: We reviewed processes negotiated to achieve linkage between the Australian Stroke Clinical Registry (AuSCR), the National Death Index, and state held hospital data. Minutes from working group meetings, national workshop meetings, and documented communications with health department staff were reviewed and summarised. RESULTS: Time from first application to receipt of data was more than two years for most state data-sets. Several challenges were unique to linkages involving identifiable data from a non-government clinical registry. Concerns about consent, the re-identification of data, duality of data custodian roles and data ownership were raised. Requirements involved the development of data flow methods, separating roles and multiple governance and ethics approvals. Approval to link death data presented the fewest barriers. CONCLUSION: To our knowledge, this is the first time in Australia that person-level data from a clinical quality registry has been linked to hospital and mortality data across multiple Australian jurisdictions. Implications for Public Health: The administrative load of obtaining linked data makes projects such as this burdensome but not impossible. An improved national centralised strategy for data linkage in Australia is urgently needed.

Rationale and design of a randomized controlled trial of pneumococcal polysaccharide vaccine for prevention of cardiovascular events: The Australian Study for the Prevention through Immunization of Cardiovascular Events (AUSPICE).

BACKGROUND: Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event. METHODS/DESIGN: The AUSPICE is a multicenter, randomized, placebo-controlled, double-blind, clinical trial to formally test whether vaccination with the pneumococcal polysaccharide vaccine protects against cardiovascular events (fatal and nonfatal acute coronary syndromes and ischemic strokes). Cardiovascular outcomes will be obtained during 4 to 5 years of follow-up, through health record linkage with state and national administrative data sets. CONCLUSION: This is the first registered randomized controlled trial (on US, World Health Organization, Australia and New Zealand trial registries) to be conducted to test whether vaccination with the pneumococcal polysaccharide vaccine will reduce cardiovascular events. If successful, vaccination can be readily extended to at-risk groups to reduce the risk of cardiovascular diseases.

A Simple Sampling Method for Estimating the Accuracy of Large Scale Record Linkage Projects.

BACKGROUND: Record linkage techniques allow different data collections to be brought together to provide a wider picture of the health status of individuals. Ensuring high linkage quality is important to guarantee the quality and integrity of research. Current methods for measuring linkage quality typically focus on precision (the proportion of incorrect links), given the difficulty of measuring the proportion of false negatives. OBJECTIVES: The aim of this work is to introduce and evaluate a sampling based method to estimate both precision and recall following record linkage. METHODS: In the sampling based method, record-pairs from each threshold (including those below the identified cut-off for acceptance) are sampled and clerically reviewed. These results are then applied to the entire set of record-pairs, providing estimates of false positives and false negatives. This method was evaluated on a synthetically generated dataset, where the true match status (which records belonged to the same person) was known. RESULTS: The sampled estimates of linkage quality were relatively close to actual linkage quality metrics calculated for the whole synthetic dataset. The precision and recall measures for seven reviewers were very consistent with little variation in the clerical assessment results (overall agreement using the Fleiss Kappa statistics was 0.601). CONCLUSIONS: This method presents as a possible means of accurately estimating matching quality and refining linkages in population level linkage studies. The sampling approach is especially important for large project linkages where the number of record pairs produced may be very large often running into millions.

Surface dust wipes are the best predictors of blood leads in young children with elevated blood lead levels.

BACKGROUND: As part of the only national survey of lead in Australian children, which was undertaken in 1996, lead isotopic and lead concentration measurements were obtained from children from 24 dwellings whose blood lead levels were ≥15 µg/dL in an attempt to determine the source(s) of their elevated blood lead. Comparisons were made with data for six children with lower blood lead levels (<10 µg/dL). METHODS: Thermal ionisation and isotope dilution mass spectrometry were used to determine high precision lead isotopic ratios (208Pb/206pb, 207Pb/206Pb and 206Pb/204Pb) and lead concentrations in blood, dust from floor wipes, soil, drinking water and paint (where available). Evaluation of associations between blood and the environmental samples was based on the analysis of individual cases, and Pearson correlations and multiple regression analyses based on the whole dataset. RESULTS AND DISCUSSION: The correlations showed an association for isotopic ratios in blood and wipes (r=0.52, 95% CI 0.19-0.74), blood and soil (r=0.33, 95% CI -0.05-0.62), and blood and paint (r=0.56, 95% CI 0.09-0.83). The regression analyses indicated that the only statistically significant relationship for blood isotopic ratios was with dust wipes (B=0.65, 95% CI 0.35-0.95); there were no significant associations for lead concentrations in blood and environmental samples. There is a strong isotopic correlation of soils and house dust (r=0.53, 95% CI 0.20-0.75) indicative of a common source(s) for lead in soil and house dust. In contrast, as with the regression analyses, no such association is present for bulk lead concentrations (r=-0.003, 95% CI -0.37-0.36), the most common approach employed in source investigations. In evaluation of the isotopic results on a case by case basis, the strongest associations were for dust wipes and blood.

RNA targets and specificity of Staufen, a double-stranded RNA-binding protein in Caenorhabditis elegans.

The Staufen family consists of proteins that possess double-stranded RNA-binding domains (dsRBDs). Staufen proteins of Drosophila and mammals regulate mRNA localization, translation, and decay. We report analysis of Staufen in Caenorhabditis elegans, which we have designated STAU-1. We focus on its biochemical properties, mRNA targets, and possible role in RNAi. We show that STAU-1 is expressed as mRNA and protein at all stages of C. elegans development. The wild-type, full-length protein, purified from bacteria, binds duplex RNA with high affinity in vitro. Purified, mutant proteins lacking single dsRBDs still bind RNA efficiently, demonstrating that no single domain is required for binding to duplex RNA (although dsRBD2 could not be tested). STAU-1 mRNA targets were identified via immunoprecipitation with specific anti-STAU-1 antibodies, followed by microarray analysis (RIP-Chip). These studies define a set of 418 likely STAU-1 mRNA targets. Finally, we demonstrate that stau-1 mutants enhance exogenous RNAi and that stau-1;eri-1 double mutants exhibit sterility and synthetic germ line defects.

Alcohol-related cognitive impairment in New South Wales hospital patients aged 50 years and over.

OBJECTIVES: The aim of this study was to describe the principal reasons for admission, medical comorbidities, interventions and outcomes of patients admitted to New South Wales hospitals with alcohol-related cognitive impairment. METHODS: We extracted data from the NSW Admitted Patient Care Database for nearly 410 000 multi-day hospital admissions from 222 public hospitals ending between July 2006 and June 2007 for people aged 50 and over. Data linkage using a unique patient identifier, derived by the Centre for Health Record Linkage identified hospital transfers and readmissions for individual patients. Using ICD10-AM codes, we identified patients with alcohol-related dementia, amnesic syndrome due to alcohol, and Wernicke's encephalopathy, their principal reasons for admission and medical comorbidities, and procedures undertaken. Outcomes were length of stay, mortality, discharge destination, and readmission. RESULTS: A total of 462 patients diagnosed with alcohol-related dementia (n = 300; 82% male, mean age 63.9 years), Wernicke's encephalopathy (n = 77) or amnesic syndrome due to alcohol (n = 126) were identified with overlap between diagnoses. Alcohol-related dementia occurred in 1.4% of dementia patients, and was more likely to occur in younger age groups and men than other types of dementia. Alcohol-related mental disorder was recorded in 70% of alcohol-related dementia multi-day admissions: dependence (52%), 'harmful use' (11%) and withdrawal (12%). Principal reasons for admission for multi-day stays included alcohol-related mental disorder (18%), liver disease (11%) and injuries/poisonings (10%). Medical comorbidity was common. Like other dementia patients, alcohol-related dementia patients had longer length of stay (mean of 15 days) than non-dementia patients and more transfers to residential care (7%). However, mortality was similar to non-dementia patients (5%). Discharge at own risk was high (3.7%). CONCLUSIONS: Alcohol-related dementia is a preventable and potentially reversible condition. Investigation of intervention strategies initiated during hospitalization are warranted.

The Hospital Dementia Services Project: age differences in hospital stays for older people with and without dementia.

BACKGROUND: People with dementia may have adverse outcomes following periods of acute hospitalization. This study aimed to explore the effects of age upon hospitalization outcomes for patients with dementia in comparison to patients without dementia. METHODS: Data extracted from the New South Wales Admitted Patient Care Database for people aged 50 years and over for the period July 2006 to June 2007 were linked to create person-based records relating to both single and multiple periods of hospitalization. This yielded nearly 409,000 multi-day periods of hospitalization relating to almost 253,000 persons. Using ICD-10-AM codes for dementia and other principal diagnoses, the relationship between age and hospitalization characteristics were examined for people with and without dementia. RESULTS: Dementia was age-related, with 25% of patients aged 85 years and over having dementia compared with 0.9% of patients aged 50-54 years. People with dementia were more likely to be admitted for fractured femurs, lower respiratory tract infections, urinary tract infections and head injuries than people without dementia. Mean length of stay for admissions for people with dementia was 16.4 days and 8.9 days for those without dementia. People with dementia were more likely than those without to be re-admitted within three months for another multi-day stay. Mortality rates and transfers to nursing home care were higher for people with dementia than for people without dementia. These outcomes were more pronounced in younger people with dementia. CONCLUSION: Outcomes of hospitalization vary substantially for patients with dementia compared with patients without dementia and these differences are frequently most marked among patients aged under 65 years.

Empirical aspects of record linkage across multiple data sets using statistical linkage keys: the experience of the PIAC cohort study.

BACKGROUND: In Australia, many community service program data collections developed over the last decade, including several for aged care programs, contain a statistical linkage key (SLK) to enable derivation of client-level data. In addition, a common SLK is now used in many collections to facilitate the statistical examination of cross-program use. In 2005, the Pathways in Aged Care (PIAC) cohort study was funded to create a linked aged care database using the common SLK to enable analysis of pathways through aged care services. Linkage using an SLK is commonly deterministic. The purpose of this paper is to describe an extended deterministic record linkage strategy for situations where there is a general person identifier (e.g. an SLK) and several additional variables suitable for data linkage. This approach can allow for variation in client information recorded on different databases. METHODS: A stepwise deterministic record linkage algorithm was developed to link datasets using an SLK and several other variables. Three measures of likely match accuracy were used: the discriminating power of match key values, an estimated false match rate, and an estimated step-specific trade-off between true and false matches. The method was validated through examining link properties and clerical review of three samples of links. RESULTS: The deterministic algorithm resulted in up to an 11% increase in links compared with simple deterministic matching using an SLK. The links identified are of high quality: validation samples showed that less than 0.5% of links were false positives, and very few matches were made using non-unique match information (0.01%). There was a high degree of consistency in the characteristics of linked events. CONCLUSIONS: The linkage strategy described in this paper has allowed the linking of multiple large aged care service datasets using a statistical linkage key while allowing for variation in its reporting. More widely, our deterministic algorithm, based on statistical properties of match keys, is a useful addition to the linker's toolkit. In particular, it may prove attractive when insufficient data are available for clerical review or follow-up, and the researcher has fewer options in relation to probabilistic linkage.

Transitions from hospital to residential aged care in Australia.

AIM: To investigate movement of people from hospital into residential aged care. METHODS: An innovative record linkage method was implemented to create a national database to investigate transitions from hospital into aged care. RESULTS: In 2001-2002, 3.2% of hospitalisations for people aged 65+ ended with admission into residential aged care. A further 5.5% were for people already living permanently in care. Nationally, more people were admitted into permanent care from hospital than from the community. Factors important in predicting admission to aged care from hospital included length of hospital stay, diagnoses, region of usual residence and hospital jurisdiction. CONCLUSION: Individually, national hospital and aged care datasets do not provide adequate information on movement between the sectors. Linking the data allowed the first national investigation into movement from hospital into aged care. Results indicate the importance of investigating interactions of service provision (both supply and demand driven) at the local level.

The acute-aged care interface: exploring the dynamics of 'bed blocking'.

OBJECTIVE: To understand the dynamics underlying 'bed-blocking' in Australian public hospitals that is frequently blamed on older patients. METHODS: Analysis of primary and secondary data of utilisation patterns of hospital and aged care services by older Australians. RESULTS: A model of the dynamics at the acute-aged care interface was developed, in which the pathway into permanent high-care Residential Aged Care (RAC) is conceptualised as competing queues for available places by applicants from the hospital, the community and from within RAC facilities. The hospital effectively becomes a safety net to accommodate people with high-care needs who cannot be admitted into RAC in a timely manner. CONCLUSION: The model provides a useful tool to explore some of the issues that give rise to access-block within the public hospital system. Access-block cannot be understood by viewing the hospital system in isolation from other sectors that support the health and well-being of older Australians.