Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction

RATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.METHODS: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations.MEASUREMENTS AND MAIN RESULTS: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.</p

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

Reports of the proportion of older people living in long‐term care: a cautionary tale from New Zealand

Abstract Objective: Population ageing is driving many countries to review health and social care policies. For many, an important component is residential long‐term care (LTC). This study uses New Zealand to ascertain the extent different reports provide consistent and accurate estimates of LTC use. Methods: We searched for available cross‐sectional information about use of LTC by people aged 65 years or over in NZ's population since 1988. In addition, for one geographic region, Auckland, we compared research survey data at three time‐points with the nearest census estimates. Results: Fifty‐eight national‐level estimates (census, subsidy payments and population surveys) were found. Since 2000, estimates of the proportion of older people reportedly living in long‐term care ranged from 3.4% to 9.2%. Comparisons with Auckland studies demonstrated improved reporting in the 2006 census. Conclusion: Estimates of the proportion of people living in residential LTC varied widely. OECD reports, often used for cross‐national comparisons, were particularly inconsistent. Implications: While estimates of the proportion of people living in residential LTC in NZ are inconsistent, improvements are evident in census and subsidy data. Reconciling new data with previous reports prior to publication may reduce variations in reporting. Improved reliability will assist understanding of within‐country trends and international comparisons, and better inform decisions shaping health services for older people

Aged Residential Care Health Utilisation Study (ARCHUS): a randomised controlled trial to reduce acute hospitalisations from residential aged care

Abstract Background For residents of long term care, hospitalisations can cause distress and disruption, and often result in further medical complications. Multi-disciplinary team interventions have been shown to improve the health of Residential Aged Care (RAC) residents, decreasing the need for acute hospitalisation, yet there are few randomised controlled trials of these complex interventions. This paper describes a randomised controlled trial of a structured multi-disciplinary team and gerontology nurse specialist (GNS) intervention aiming to reduce residents’ avoidable hospitalisations. Methods/Design This Aged Residential Care Healthcare Utilisation Study (ARCHUS) is a cluster- randomised controlled trial (n = 1700 residents) of a complex multi-disciplinary team intervention in long-term care facilities. Eligible facilities certified for residential care were selected from those identified as at moderate or higher risk of resident potentially avoidable hospitalisations by statistical modelling. The facilities were all located in the Auckland region, New Zealand and were stratified by District Health Board (DHB). Intervention The intervention provided a structured GNS intervention including a baseline facility needs assessment, quality indicator benchmarking, a staff education programme and care coordination. Alongside this, three multi-disciplinary team (MDT) meetings were held involving a geriatrician, facility GP, pharmacist, GNS and senior nursing staff. Outcomes Hospitalisations are recorded from routinely-collected acute admissions during the 9-month intervention period followed by a 5-month follow-up period. ICD diagnosis codes are used in a pre-specified definition of potentially reducible admissions. Discussion This randomised-controlled trial will evaluate a complex intervention to increase early identification and intervention to improve the health of residents of long term care. The results of this trial are expected in early 2013. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN 12611000187943</p

Cohort profile: Te Puawaitanga o Nga Tapuwae Kia Ora Tonu, life and living in advanced age: a cohort study in New Zealand (LiLACS NZ)

The ageing of the population globally and in New Zealand (NZ) was the main driver for this study. In Aoteoroa, New Zealand, little is known about Māori and non-Māori of advanced age, yet population projections predict a trebling of the number of Māori and a doubling of non-Māori octogenarians in the next 10 years. 1 The impact of common health conditions may differ for older people when compared with their younger counterparts. The importance of social support and practical assistance may vary according to the psychological and functional ability of those in advanced age. The incidence and predictors of falls and fractures in advanced age are unknown, as is the relationship between traditional and novel cardiovascular risk factors and cardiovascular outcomes. The relationship between dietary intake, nutritional status and functional decline in advanced age may point the way to food strategies for better health

Socioeconomic correlates of quality of life for non-Māori in advanced age: Te Puāwaitanga o Nga Tapuwae Kia ora Tonu. Life and Living in Advanced Age: a cohort study in New Zealand (LiLACS NZ)

AIM: To establish socioeconomic and cultural profiles and correlates of quality of life (QoL) in non-Māori of advanced age. METHOD: A cross sectional analysis of the baseline data of a cohort study of 516 non-Māori aged 85 years living in the Bay of Plenty and Rotorua areas of New Zealand. Socioeconomic and cultural characteristics were established by face-to-face interviews in 2010. Health-related QoL (HRQoL) was assessed with the SF-12. RESULTS: Of the 516 non-Māori participants enrolled in the study, 89% identified as New Zealand European, 10% other European, 1% were of Pacific, Asian or Middle Eastern ethnicity; 20% were born overseas and half of these identified as 'New Zealand European.' More men were married (59%) and more women lived alone (63%). While 89% owned their own home, 30% received only the New Zealand Superannuation as income and 22% reported that they had 'just enough to get along on'. More than 85% reported that they had sufficient practical and emotional support; 11% and 6% reported unmet need for practical and emotional support respectively. Multivariate analyses showed that those with unmet needs for practical and emotional support had lower mental HR QoL (p<0.005). Reporting that family were important to wellbeing was associated with higher mental HR QoL (p=0.038). Those that did not need practical help (p=0.047) and those that reported feeling comfortable with their money situation (0.0191) had higher physical HRQoL. High functional status was strongly associated with both high mental and high physical HR QoL (p<0.001). CONCLUSION: Among our sample of non-Māori people of advanced age, those with unmet support needs reported low HRQoL. Functional status was most strongly associated with mental and physical HRQoL