Exploring patterns of response across the lifespan: the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study

Abstract Background With declining rates of participation in epidemiological studies there is an important need to attempt to understand what factors might affect response. This study examines the pattern of response at different adult ages within a contemporary cross-sectional population-based cohort, the Cambridge Centre for Ageing and Neuroscience (Cam-CAN). Methods Using logistic regression, we investigated associations between age, gender and Townsend deprivation level for both participants and non-participants. Weighted estimates of the odds ratios with confidence intervals for each demographic characteristic were calculated. Reasons given for refusal were grouped into three broad categories: ‘active’, ‘passive’ and illness preventing interview. Results An association of age and participation was found, with individuals in middle age groups more likely to participate (age group 48–57 OR: 1.8, 95% CI: 1.5–2.2 and age group 58–67 OR: 2.1, 95% CI: 1.7–2.4). Overall, there was no difference in participation between men and women. An association with deprivation was found, with those living in the most deprived areas being the least willing to participate (fifth quintile OR: 0.6, 95% CI: 0.5–0.7). An interaction between age and gender was found whereby younger women and older men were more likely to agree to participate (p = 0.01). Conclusion Our findings highlight some of the factors affecting recruitment into epidemiological studies in the UK and suggest that targeted age-specific recruitment strategies might be needed to increase participation rates in future cohort investigations

Who Lives Where and Does It Matter? Changes in the Health Profiles of Older People Living in Long Term Care and the Community over Two Decades in a High Income Country.

BACKGROUND: There have been fundamental shifts in the attitude towards, access to and nature of long term care in high income countries. The proportion and profile of the older population living in such settings varies according to social, cultural, and economic characteristics as well as governmental policies. Changes in the profiles of people in different settings are important for policy makers and care providers. Although details will differ, how change occurs across time is important to all, including lower and middle income countries developing policies themselves. Here change is examined across two decades in England. METHODS AND FINDINGS: Using the two Cognitive Function and Ageing Studies (CFAS I: 77% response, CFAS II: 56% response), two population based studies of older people carried out in the same areas conducted two decades apart, the study diagnosis of dementia using the Automated Geriatric Examination for Computer Assisted Taxonomy, health and wellbeing were examined, focusing on long term care. The proportion of individuals with three or more health conditions increased for everyone living in long term care between CFAS I (47.6%, 95% CI: 42.3-53.1) and CFAS II (62.7%, 95% CI: 54.8-70.0) and was consistently higher in those without dementia compared to those with dementia in both studies. Functional impairment measured by activities of daily living increased in assisted living facilities from 48% (95% CI: 44%-52%) to 67% (95% CI: 62%-71%). CONCLUSIONS: Health profiles of residents in long term care have changed dramatically over time. Dementia prevalence and reporting multiple health conditions have increased. Receiving care in the community puts pressure on unpaid carers and formal services; these results have implications for policies about supporting people at home as well as for service provision within long term care including quality of care, health management, cost, and the development of a skilled, caring, and informed workforce.CFAS II has been funded through a grant from the Medical Research Council (grant number G0601022). CFAS I was also funded through the Medical Research Council (grant number G9901400).This is the final version of the article. It first appeared from PLOS at http://dx.doi.org/10.1371/journal.pone.0161705

The contribution of multiple long-term conditions to widening inequalities in disability-free life expectancy over two decades: Longitudinal analysis of two cohorts using the Cognitive Function and Ageing Studies.

BACKGROUND: : Disability-free life expectancy (DFLE) inequalities by socioeconomic deprivation are widening, alongside rising prevalence of multiple long-term conditions (MLTCs). We use longitudinal data to assess whether MLTCs contribute to the widening DFLE inequalities by socioeconomic deprivation. METHODS: : The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those ≥65 years, conducted in three areas in England. Baseline occurred in 1991 (CFAS I, n=7635) and 2011 (CFAS II, n=7762) with two-year follow-up. We defined disability as difficulty in activities of daily living, MLTCs as the presence of at least two of nine health conditions, and socioeconomic deprivation by area-level deprivation tertiles. DFLE and transitions between disability states and death were estimated from multistate models. FINDINGS: : For people with MLTCs, inequalities in DFLE at age 65 between the most and least affluent widened to around 2.5 years (men:2.4 years, 95% confidence interval (95%CI) 0.4-4.4; women:2.6 years, 95%CI 0.7-4.5) by 2011. Incident disability reduced for the most affluent women (Relative Risk Ratio (RRR):0.6, 95%CI 0.4-0.9), and mortality with disability reduced for least affluent men (RRR:0.6, 95%CI 0.5-0.8). MLTCs prevalence increased only for least affluent men (1991: 58.8%, 2011: 66.9%) and women (1991: 60.9%, 2011: 69.1%). However, DFLE inequalities were as large in people without MLTCs (men:2.4 years, 95%CI 0.3-4.5; women:3.1 years, 95% CI 0.8-5.4). INTERPRETATION: : Widening DFLE inequalities were not solely due to MLTCs. Reduced disability incidence with MLTCs is possible but was only achieved in the most affluent

Healthy ageing for all? Comparisons of socioeconomic inequalities in health expectancies over two decades in the Cognitive Function and Ageing Studies I and II

Background: Despite increasing life expectancy (LE), cross-sectional data show widening inequalities in disability-free LE (DFLE) by socioeconomic status (SES) in many countries. We use longitudinal data to better understand trends in DFLE and years independent (IndLE) by SES, and how underlying transitions contribute. Methods: The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those aged ≥65 years in three English centres (Newcastle, Nottingham, Cambridgeshire), with baseline around 1991 (CFAS I, n = 7635) and 2011 (CFAS II, n = 7762) and 2-year follow-up. We defined disability as difficulty in activities of daily living (ADL), dependency by combining ADLs and cognition reflecting care required, and SES by area-level deprivation. Transitions between disability or dependency states and death were estimated from multistate models. Results: Between 1991 and 2011, gains in DFLE at age 65 were greatest for the most advantaged men and women [men: 4.7 years, 95% confidence interval (95% CI) 3.3-6.2; women: 2.8 years, 95% CI 1.3-4.3]. Gains were due to the most advantaged women having a reduced risk of incident disability [relative risk ratio (RRR):0.7, 95% CI 0.5-0.8], whereas the most advantaged men had a greater likelihood of recovery (RRR: 1.8, 95% CI 1.0-3.2) and reduced disability-free mortality risk (RRR: 0.4, 95% CI 0.3-0.6]. Risk of death from disability decreased for least advantaged men (RRR: 0.7, 95% CI 0.6-0.9); least advantaged women showed little improvement in transitions. IndLE patterns across time were similar. Conclusions: Prevention should target the most disadvantaged areas, to narrow inequalities, with clear indication from the most advantaged that reduction in poor transitions is achievable

A Retrospective Survey of HIV Drug Resistance Among Patients 1 Year After Initiation of Antiretroviral Therapy at 4 Clinics in Malawi

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention

Thermal physiology of three sympatric small mammals from southern Africa

Please read abstract in the article.ThE National Research Foundationhttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-79982020-01-01hj2018Mammal Research InstituteZoology and Entomolog

The influence of photoperiod on the reproductive physiology of the greater red musk shrew (Crocidura flavescens)

Photoperiodism involves the use of both absolute measures of day length and the direction in which day length is changing as a cue for regulating seasonal changes in physiology and behaviour so that birth and lactation coincide with optimal resource availability, increasing offspring survival. Induced ovulation and opportunistic breeding is often found in species that are predominantly solitary and territorial. In this study, the photoperiodic reproductive responses of male greater red musk shrews (Crocidura flavescens (I. Geoffroy Saint-Hilaire, 1827)) were investigated in the laboratory. The presence of spermatozoa regardless of the light cycle, suggest that although the shrews are photoresponsive, they may be capable of breeding throughout the year. Significantly greater testicular volume and seminiferous tubule diameter following exposure to a short day-light cycle suggests that these animals may have breeding peaks that correspond to short days. The presence of epidermal spines on the penis indicates that the shrew is likely also an induced ovulator. Flexible breeding patterns combined with induced ovulation affords this solitary species the greatest chance of reproductive success.National Research Foundation (NRF; GUN 64756).http://www.nrcresearchpress.com/journal/cjzhb2016Zoology and Entomolog

Forum Report: Issues in the Evaluation of Diagnostic Tests, Use of Historical Controls, and Merits of the Current Multicenter Collaborative Groups

This forum report contains conclusions about 3 different issues relevant to conducting clinical trials in deep mycoses. (1) Trials of diagnostic tests for deep mycoses must define the population appropriate for testing and the clinical question being asked. The unanswered question for the serum Aspergillus galactomannan assay is whether knowledge of results can change use of empirical therapy to treat febrile patients at high risk of invasive aspergillosis. (2) Use of historical controls is suboptimal but offers a pragmatic solution for studying rare mycoses; use of contemporaneous controls, matched for critical variables and evaluated by a blinded data review committee using detailed criteria, appears optimal. (3) Established groups of independent investigators, such as the European Organization for Research on Treatment of Cancer's Invasive Fungal Infections Group and National Institute of Allergy and Infectious Diseases's Bacteriology and Mycology Study Group, provide a pool of experienced investigators, defined operating rules, impartiality, and specialized expertise. Considering the enormous investment required for adequately powered efficacy trials of antifungal agents and the importance of these trials to guide clinical practice, use of collaborative groups outweighs the extra administrative time that is sometimes require

Forum Report: Issues in the Design of Trials of Drugs for the Treatment of Invasive Aspergillosis

A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable” in addition to "proven” aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable” aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practic

Forum Report: Issues in Clinical Trials of Empirical Antifungal Therapy in Treating Febrile Neutropenic Patients

There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of feve