Ethnic Variations in the Quality Use of Medicines in Older Adults: Maori and Non-Maori in Aotearoa New Zealand.

In Aotearoa New Zealand (NZ), ethnic inequities in health outcomes exist. Non-Maori experience better access to healthcare than Maori, including access to the quality use of medicines. Quality medicines use requires that medicines provide maximal therapeutic benefit with minimal harm. As older adults are more at risk of harm from medicines, and, because inequities are compounded with age, Maori older adults may be at more risk of medicines-related harm than younger and non-Maori populations. This narrative review examined ethnic variation in the quality use of medicines, including medicines utilisation and associated clinical outcomes, between Maori and non-Maori older adult populations in NZ. The review was structured around prevalence of medicine utilisation by medicine class and in particular disease states; high-risk medicines; polypharmacy; prevalence of potentially inappropriate prescribing (PIP); and association between PIP and clinical outcomes. 22 studies were included in the review. There is ethnic variation in the access to medicines in NZ, with Maori older adults often having reduced access to particular medicine types, or in particular disease states, compared with non-Maori older adults. Maori older adults are less likely than non-Maori to be prescribed medicines inappropriately, as defined by standardised tools; however, PIP is more strongly associated with adverse outcomes for Maori than non-Maori. This review identifies that inequities in quality medicines use exist and provides a starting point to develop pro-equity solutions. The aetiology of inequities in the quality use of medicines is multifactorial and our approaches to addressing the inequitable ethnic variation also need to be.

Falls risk factor assessment and secondary prevention in the older old.

AIMS: Falls are common in 80-plus year-olds and there is evidence available in terms of risk factors and prevention measures. We aimed to review falls risk factor assessment and secondary prevention strategies in patients in this age group presenting acutely to services other than older adult health services at Waitemata District Health Board. METHODS: We retrospectively reviewed electronic hospital records of those >80 years presenting to acute services with a primary or secondary diagnosis of a fall, or fall-related injury. Admission characteristics, risk factor identification and subsequent referrals for falls prevention were recorded. Six-month outcomes including readmissions and mortality were assessed. RESULTS: One hundred and thirty-eight discharge summaries were reviewed (71% female, median age 89). Thirty-one percent had a previous fall-related hospital admission in the six months prior. There was high prevalence of psychoactive medications (51%) and falls-related cardiovascular drugs (78%) at discharge. No patients were referred for falls prevention programmes or geriatric assessment at discharge. At six months 19% had died and 44% had been readmitted. CONCLUSIONS: There are inadequate falls prevention referrals, indicating a quality of care gap. The older age group presenting to acute services have high rates of polypharmacy, hospitalisations and death.

Patterns of multi-morbidity and prediction of hospitalisation and all-cause mortality in advanced age.

Background: multi-morbidity is associated with poor outcomes and increased healthcare utilisation. We aim to identify multi-morbidity patterns and associations with potentially inappropriate prescribing (PIP), subsequent hospitalisation and mortality in octogenarians. Methods: life and Living in Advanced Age; a Cohort Study in New Zealand (LiLACS NZ) examined health outcomes of 421 Maori (indigenous to New Zealand), aged 80-90 and 516 non-Maori, aged 85 years in 2010. Presence of 14 chronic conditions was ascertained from self-report, general practice and hospitalisation records and physical assessments. Agglomerative hierarchical cluster analysis identified clusters of participants with co-existing conditions. Multivariate regression models examined the associations between clusters and PIP, 48-month hospitalisations and mortality. Results: six clusters were identified for Maori and non-Maori, respectively. The associations between clusters and outcomes differed between Maori and non-Maori. In Maori, those in the complex multi-morbidity cluster had the highest prevalence of inappropriately prescribed medications and in cluster 'diabetes' (20% of sample) had higher risk of hospitalisation and mortality at 48-month follow-up. In non-Maori, those in the 'depression-arthritis' (17% of the sample) cluster had both highest prevalence of inappropriate medications and risk of hospitalisation and mortality. Conclusions: in octogenarians, hospitalisation and mortality are better predicted by profiles of clusters of conditions rather than the presence or absence of a specific condition. Further research is required to determine if the cluster approach can be used to target patients to optimise resource allocation and improve outcomes.

Drug Burden and its Association with Falls Among Older Adults in New Zealand: A National Population Cross-Sectional Study.

BACKGROUND: Adverse outcomes associated with advanced diseases are often exacerbated by polypharmacy. OBJECTIVES: The current study investigated an association between exposure to anticholinergic and sedative medicines and falls in community-dwelling older people, after controlling for potential confounders. METHODS: We conducted a retrospective cross-sectional study of a continuously recruited national cohort of community-dwelling New Zealanders aged 65 years and over. Participants had an International Resident Assessment Instrument-Home Care (interRAI-HC) assessment between 1 September 2012 and 31 January 2016. InterRAI-HC is a comprehensive, multi-domain, standardised assessment. This study captured 18 variables, including fall frequency, from the interRAI. These data were deterministically matched with the Drug Burden Index (DBI) for each participant, derived from an anonymised national dispensed pharmaceuticals database. DBI groupings were statistically ascertained, and ordinal regression models employed. RESULTS: Overall, there were 71,856 participants, with a mean age of 82.7 years (range 65-106); 43,802 (61.0%) were female, and 63,578 (88.5%) were New Zealand European. In unadjusted and adjusted analyses, DBI groupings were related to falls (p < 0.001). A DBI score > 3 was associated with a 41% increase in falls compared with a DBI score of 0 (p < 0.001). There was a 'dose-response' relationship between DBI levels and falls risk. CONCLUSIONS: DBI was found to be independently and positively associated with a greater risk of falls in this cohort after adjustment for 18 known confounders. We suggest that the DBI could be a valuable tool for clinicians to use alongside electronic prescribing to help reduce falls in older people.

Testosterone in advance age: a New Zealand longitudinal cohort study: Life and Living in Advanced Age (Te Puawaitanga o Nga Tapuwae Kia Ora Tonu).

OBJECTIVES: Serum testosterone (T) levels in men decline with age. Low T levels are associated with sarcopenia and frailty in men aged >80 years. T levels have not previously been directly associated with disability in older men. We explored associations between T levels, frailty and disability in a cohort of octogenarian men. SETTING: Data from all men from Life and Living in Advanced Age Cohort Study in New Zealand, a longitudinal cohort study in community-dwelling older adults. PARTICIPANTS: Community-dwelling (>80 years) adult men excluding those receiving T treatment or with prostatic carcinoma. OUTCOMES MEASURES: Associations between baseline total testosterone (TT) and calculated free testosterone (fT), frailty (Fried scale) and disability (Nottingham Extended Activities of Daily Living scale (NEADL)) (baseline and 24 months) were examined using multivariate regression and Wald's χ2 techniques. Subjects with the lowest quartile of baseline TT and fT values were compared with those in the upper three quartiles. RESULTS: Participants: 243 men, mean (SD) age 83.7 (2.0) years. Mean (SD) TT=17.6 (6.8) nmol/L and fT=225.3 (85.4) pmol/L. On multivariate analyses, lower TT levels were associated with frailty: ß=0.41, p=0.017, coefficient of determination (R2)=0.10 and disability (NEADL) (ß=-1.27, p=0.017, R2=0.11), low haemoglobin (ß=-7.38, p=0.0016, R2=0.05), high fasting glucose (ß=0.38, p=0.038, R2=0.04) and high C reactive protein (CRP) (ß=3.57, p=0.01, R2=0.06). Low fT levels were associated with frailty (ß=0.39, p=0.024, R2=0.09) but not baseline NEADL (ß=-1.29, p=0.09, R2=0.09). Low fT was associated with low haemoglobin (ß=-7.83, p=0.0008, R2=0.05) and high CRP (ß=2.86, p=0.04, R2=0.05). Relationships between baseline TT and fT, and 24-month outcomes of disability and frailty were not significant. CONCLUSIONS: In men over 80 years, we confirm an association between T levels and baseline frailty scores. The new finding of association between T levels and disability is potentially relevant to debates on T supplementation in older men, though, as associations were not present at 24 months, further work is needed.

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12.

BACKGROUND: Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants. OBJECTIVE: To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation. METHODS: 3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV1 were tested in cases. We followed-up signals of interest (p<10(-5)) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays. RESULTS: Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10(-6)). In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10(-6)). We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5. No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10(-7)). CONCLUSIONS: This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study.

Medication use and potentially inappropriate medications in those with limited prognosis living in residential aged care.

AIM: To compare the prevalence in residential aged care (RAC) of preventative and potentially inappropriate medications (PIMs) in those who died within 12 months versus those alive after 12 months. METHODS: Firstly, a cross-sectional survey of 6196 people living in RAC in Auckland. Secondly, a research physician searched electronic hospital records in one District Health Board for a sub-sample (n = 222) of these residents. Classes of medications and dates of death were obtained from the Ministry of Health databases. Those who died versus those alive at 12 months were compared. RESULTS: Over half of the 6196 participants received antihypertensives and/or antiplatelet agents. Cardiovascular preventative medications were significantly more common in those who died within 12 months. Seventy percent in high-level care received psychotropics. PIMs were commonly used. CONCLUSIONS: Use of preventative medications is common in RAC, especially during the last year of life. Psychotropics are very commonly used, despite being potentially inappropriate.

Residential aged care: the de facto hospice for New Zealand's older people.

AIM: To describe short-term mortality among residential aged care (RAC) residents in Auckland, New Zealand. METHOD: Prospective follow-up, 6828 residents (median age 86 years, 69.8% women) from census-type survey (10/9/2008); 152 facilities. Mortality data from central sources. RESULTS: Eight hundred and sixty-one (12.6%) died by 6 months. Survival related to RAC length of stay before the survey: those resident <1 month (subgroup, n = 380) having 80.0% survival, 1-6 months 83.2% and >6 months 87.4% (P < 0.0001). In those admitted to private hospital from acute hospital (n = 104 of the subgroup of 380), 6-month mortality was 36.5% (P < 0.0001 vs other 'short stayers'). Significant mortality predictors were: private hospital admission from acute hospital (hazard ratio (HR) = 2.02), unscheduled GP visit during the prior 2 weeks (HR = 1.90), personal care disability (HR = 1.90) and acute hospital admission number during the previous 2 years (≥3; HR = 5.40). CONCLUSIONS: RAC mortality (especially post admission) is high. Training and resource in the sector should reflect this.

Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels.

The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17 × 10(-7)), which was also observed in a COPD population (combined P=5.04 × 10(-12)). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects. In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases.

Life and living in advanced age: a cohort study in New Zealand--e Puawaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: study protocol.

BACKGROUND: The number of people of advanced age (85 years and older) is increasing and health systems may be challenged by increasing health-related needs. Recent overseas evidence suggests relatively high levels of wellbeing in this group, however little is known about people of advanced age, particularly the indigenous Maori, in Aotearoa, New Zealand. This paper outlines the methods of the study Life and Living in Advanced Age: A Cohort Study in New Zealand. The study aimed to establish predictors of successful advanced ageing and understand the relative importance of health, frailty, cultural, social & economic factors to successful ageing for Maori and non-Maori in New Zealand. METHODS/DESIGN: A total population cohort study of those of advanced age. Two cohorts of equal size, Maori aged 80-90 and non-Maori aged 85, oversampling to enable sufficient power, were enrolled. A defined geographic region, living in the Bay of Plenty and Lakes District Health Board areas of New Zealand, defined the sampling frame. Runanga (Maori tribal organisations) and Primary Health Organisations were subcontracted to recruit on behalf of the University. Measures--a comprehensive interview schedule was piloted and administered by a trained interviewer using standardised techniques. Socio-demographic and personal history included tribal affiliation for Maori and participation in cultural practices; physical and psychological health status used standardised validated research tools; health behaviours included smoking, alcohol use and nutrition risk; and environmental data included local amenities, type of housing and neighbourhood. Social network structures and social support exchanges are recorded. Measures of physical function; gait speed, leg strength and balance, were completed. Everyday interests and activities, views on ageing and financial interests complete the interview. A physical assessment by a trained nurse included electrocardiograph, blood pressure, hearing and vision, anthropometric measures, respiratory function testing and blood samples. DISCUSSION: A longitudinal study of people of advanced age is underway in New Zealand. The health status of a population based sample of older people will be established and predictors of successful ageing determined.

The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokers.

BACKGROUND: We have previously shown evidence that polymorphisms within genes controlling leukotriene B4 (LTB4) production (ALOX5AP and LTA4H) are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB4 in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB4 (LTB4R1 and LTB4R2) influence baseline lung function and COPD susceptibility/severity in smokers. METHODS: Eight ALOX5AP, six LTA4H and six LTB4R single nucleotide polymorphisms (SNPs) were genotyped in a UK Smoking Cohort (n = 992). Association with baseline lung function (FEV1 and FEV1/FVC ratio) was determined by linear regression. Logistic regression was used to compare smoking controls (n = 176) with spirometry-defined COPD cases (n = 599) and to more severe COPD cases (GOLD stage 3 and 4, n = 389). RESULTS: No association with ALOX5AP, LTA4H or LTB4R survived correction for multiple testing. However, we showed modest association with LTA4H rs1978331C (intron 11) with increased FEV1 (p = 0.029) and with increased FEV1/FVC ratio (p = 0.020). CONCLUSIONS: These data suggest that polymorphisms spanning ALOX5AP, LTA4H and the LTB4R locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for LTA4H rs1978331C (intron 11) in determining baseline FEV1 and FEV1/FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.

Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment in intermediate-frail and frail elderly men?

CONTEXT: Short-term testosterone (T) treatment in frail elderly men improves muscle mass and strength. It is unclear whether these effects can be maintained post treatment. OBJECTIVE: To assess the durability of androgen effects in frail men. DESIGN AND SETTING: Single center, randomized, double-blind, placebo-controlled trial to investigate the effects of 6 months T (25-75 mg daily) on muscle strength, body composition, physical function, and quality of life (QoL). Participants were assessed at the end of treatment (6 months) and 6 months after treatment cessation (12 months). PARTICIPANTS: 274 intermediate-frail and frail elderly men aged 65-90 years with low T levels. RESULTS: Mean T increased from 11.1 (3.1) nmol/liter at baseline to 18.4 (3.5) nmol/liter at 6 months, then declined to 10.5 (3.7) nmol/L at 12 months, in the T-treated group. Isometric knee extension peak torque increased in the T-treated group compared with placebo to give an adjusted mean difference (95% CI) between groups of 8.1 (-0.2 to 16.5) Nm at 6 months. Lean mass increased in the T-treated group giving a difference between groups of 1.2 (0.8 to 1.7) kg at 6 months. Somatic and sexual symptoms improved during treatment. None of these differences between groups remained at 12 months. Prostate specific antigen (PSA) levels and haematocrit increased slightly during treatment but returned to baseline by 12 months. CONCLUSION: The effects of 6-month T treatment on muscle strength, lean mass, and QoL in frail men are not maintained at 6 months post treatment.

PLAUR polymorphisms and lung function in UK smokers.

BACKGROUND: We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene. In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers. METHODS: 25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992). Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV(1), FEV(1)/FVC) in all smokers. Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression. RESULTS: Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV(1) respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV(1)/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent. Interestingly, several of these associations were driven by male smokers not females. CONCLUSION: This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers. However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers. PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling.

Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

Pulmonary rehabilitation programmes in the UK: a national representative survey.

BACKGROUND: Respiratory disease is a common cause of disability in middle and late life. Pulmonary rehabilitation programmes improve exercise capacity and quality of life in patients with chronic lung diseases. However, currently, in the UK the availability of pulmonary rehabilitation programmes and their characteristics are unknown. METHODS: We surveyed pulmonary rehabilitation programmes in terms of number, size, duration, content of educational and exercise programme, and staffing. We mailed a 17-item questionnaire previously used in Canadian study to 190 physiotherapy departments within acute hospitals in UK. RESULTS: One hundred and seventy-one (90%) responses were received. Sixty-eight centres (40%) run a pulmonary rehabilitation programme (99% outpatient). Mean age of subjects was > or = 70 in only seven centres (10%), though most cited no upper age limit. Ninety-nine per cent of centres incorporated exercise training. Programmes recruited a median group size of 10 patients (range 4-17) at a given time with a median duration of eight weeks (range 5-24) weeks. Most (71%) run twice per week with a duration of 2 hours (63%). Only half offered smoking cessation support, and a minority gave advice on coping with disease, travel and sexual matters. CONCLUSION: Around 40% of surveyed hospitals run a pulmonary rehabilitation programme and most of the programmes are similar in their format, content and staffing. Despite the high prevalence of chronic obstructive pulmonary disease (COPD)-related disability in old age most programmes chiefly included younger subjects. This may reflect lack of referral. Greater awareness and expansion of availability of programmes is indicated.