Does melatonin improve sleep in older people? A randomised crossover trial

Abstract Study objective: to determine whether melatonin will improve quality of sleep in healthy older people with age-related sleep maintenance problems. Design: a double blind randomised placebo controlled crossover trial in healthy older volunteers. Setting: a largely urban population, Auckland, New Zealand. Participants: participants were part of the larger Possible Role of Melatonin in Sleep of Elders study. People 65 years or more of age were recruited through widespread advertising. We screened 414 potential participants by mail using the Pittsburgh Sleep Quality Index, and selected 194 for clinic interview. Exclusions included depression, cognitive impairment, hypnosedative medications, sleep phase abnormalities, medical and/or environmental problems that might impair sleep. Twenty normal and 20 problem sleepers were randomly allocated for this study from a larger sample of 60 normal and 60 problem sleepers. Measurements and results: 24-hour urine 6-sulphatoxymelatonin was measured to estimate melatonin secretion in each participant. Five milligrams of melatonin, or matching placebo were each taken at bedtime for 4 weeks, separated by a 4-week washout period. Sleep quality was measured using sleep diaries, the Leeds Sleep Evaluation Questionnaire, and actigraphy. There was a significant difference between the groups in self-reported sleep quality indicators at entry, but no difference in melatonin secretion. Melatonin did not significantly improve any sleep parameter measured in either group. Conclusion: 5 mg of fast release melatonin taken at bedtime does not improve the quality of sleep in older people with age-related sleep maintenance problems

Testosterone in advance age: a New Zealand longitudinal cohort study: life and living in advanced age (te puāwaitanga o ngā 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\u27s 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: β=0.41, p=0.017, coefficient of determination (R2)=0.10 and disability (NEADL) (β=-1.27, p=0.017, R2=0.11), low haemoglobin (β=-7.38, p=0.0016, R2=0.05), high fasting glucose (β=0.38, p=0.038, R2=0.04) and high C reactive protein (CRP) (β=3.57, p=0.01, R2=0.06). Low fT levels were associated with frailty (β=0.39, p=0.024, R2=0.09) but not baseline NEADL (β=-1.29, p=0.09, R2=0.09). Low fT was associated with low haemoglobin (β=-7.83, p=0.0008, R2=0.05) and high CRP (β=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

The relative importance of COVID‐19 pandemic impacts on biodiversity conservation globally

Abstract: The COVID‐19 pandemic has had an enormous impact on almost all aspects of human society and endeavor; the natural world and its conservation have not been spared. Through a process of expert consultation, we identified and categorized, into 19 themes and 70 subthemes, the ways in which biodiversity and its conservation have been or could be affected by the pandemic globally. Nearly 60% of the effects have been broadly negative. Subsequently, we created a compendium of all themes and subthemes, each with explanatory text, and in August 2020 a diverse group of experienced conservationists with expertise from across sectors and geographies assessed each subtheme for its likely impact on biodiversity conservation globally. The 9 subthemes ranked highest all have a negative impact. These were, in rank order, governments sidelining the environment during their economic recovery, reduced wildlife‐based tourism income, increased habitat destruction, reduced government funding, increased plastic and other solid waste pollution, weakening of nature‐friendly regulations and their enforcement, increased illegal harvest of wild animals, reduced philanthropy, and threats to survival of conservation organizations. In combination, these impacts present a worrying future of increased threats to biodiversity conservation but reduced capacity to counter them. The highest ranking positive impact, at 10, was the beneficial impact of wildlife‐trade restrictions. More optimistically, among impacts ranked 11‐20, 6 were positive and 4 were negative. We hope our assessment will draw attention to the impacts of the pandemic and, thus, improve the conservation community's ability to respond to such threats in the future

Life and living in advanced age: a cohort study in New Zealand - Te Puāwaitanga o Nga Tapuwae Kia Ora Tonu, LiLACS NZ: Study protocol

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 Māori, 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 Māori and non-Māori in New Zealand

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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

Likelihood of residential aged care use in later life: a simple approach to estimation with international comparison

Abstract Objectives: In New Zealand (NZ), place of death among decedents aged 65+ years has been reported as residential aged care (RAC, 38%), acute hospital (34%) or elsewhere (28%). However, lifetime risk of use of RAC (or nursing homes) is unknown. A simple method of estimation is demonstrated for NZ and Australia, with comparisons to other countries. Methods: Deaths of RAC residents in acute hospitals were estimated for NZ from four separate studies and added to deaths occurring in RAC, to derive the likelihood of using RAC after age 65 years. Academic and other sources were searched for comparative reports. Results: An estimated 18% of RAC residents died in acute hospital in NZ. When added to those who died in RAC, the proportion using RAC for late‐life care was estimated at over 47% (66% if aged 85+ years). Of 12 US reports, the median report was 41%. Elsewhere, Finland was 47%, UK 28%, Australia 34% to 53%, and Germany 22% & 26%. Conclusions: Simple estimation using existing data demonstrates that RAC in late life is common. Implications: Late‐life care services will continue to evolve. Monitoring RAC utilisation is necessary for informed debate about palliative care provision in RAC, use of hospital by RAC residents and for planning and policy setting