Michael P. Gardner

Comprehensive geriatric assessment for older adults admitted to hospital

BACKGROUNDnComprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary diagnostic process to determine the medical, psychological and functional capabilities of a frail elderly person in order to develop a co-ordinated and integrated plan for treatment and long-term follow up.nnnOBJECTIVESnWe sought to evaluate the effectiveness of CGA in hospital for older adults admitted as an emergency.nnnSEARCH STRATEGYnWe searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), the Database of Abstracts of Reviews of Effects (DARE), MEDLINE, EMBASE, CINAHL and AARP Ageline, and handsearched high-yield journals.nnnSELECTION CRITERIAnWe searched for randomised controlled trials comparing CGA (whether by mobile teams or in designated wards) to usual care.nnnDATA COLLECTION AND ANALYSISnTwo review authors initially assessed eligibility and trial quality and extracted published data.nnnMAIN RESULTSnTwenty-two trials evaluating 10,315 participants in six countries were identified. Patients in receipt of CGA were more likely to be alive and in their own homes at up to six months (OR 1.25, 95% CI 1.11 to 1.42, P = 0.0002) and at the end of scheduled follow up (median 12 months) (OR 1.16, 95% CI 1.05 to 1.28, P = 0.003) when compared to general medical care. In addition, patients were less likely to be institutionalised (OR 0.79, 95% CI 0.69 to 0.88, P < 0.0001). They were less likely to suffer death or deterioration (OR 0.76, 95% CI 0.64 to 0.90, P = 0.001), and were more likely to experience improved cognition in the CGA group (OR 1.11, 95% CI 0.20 to 2.01, P = 0.02). Subgroup interaction in the primary outcomes suggests that the effects of CGA are primarily the result of CGA wards.nnnAUTHORS CONCLUSIONSnComprehensive geriatric assessment increases a patients likelihood of being alive and in their own home at up to 12 months.

Gender and telomere length: Systematic review and meta-analysis

BACKGROUNDnIt is widely believed that females have longer telomeres than males, although results from studies have been contradictory.nnnMETHODSnWe carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression.nnnRESULTSnMeta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error.nnnCONCLUSIONSnTelomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.

The viable cryopreserved allograft aortic valve.

One hundred and twenty‐four patients underwent aortic valve replacement with a nonviable 4°C refrigerated aortic allograft valve. One hundred and eighty‐four patients underwent aortic valve replacement with a viable cryopreserved aortic allograft valve in a later era. The longest follow‐up was 16 years for the group with the nonviable valve and 11 years for the group with the viable valves. Within this time frame, reoperation was required in 23 patients with nonviable valves for leaflet perloration or rupture whereas no patients in the group with viable valves developed this complication (p < 0.0001). The prevalence of endocarditis and thromboembolism was very low in both groups. Viability of leaflet tissue is associated with an important improvement in durability over nonviable allograft valves. Consequently, long‐term follow‐up results of allograft valves might be best expressed in terms of viability. The current evidence suggests that the viable cells are donor in origin. The viable cryopreserved aortic allograft valve offers significant advantages over current nonviable allograft valves, mechanical valves, and bioprostheses.

Why Does HIV Infection Not Lead to Disseminated Strongyloidiasis

We investigated the hypothesis that host immunosuppression due to advancing human immunodeficiency virus (HIV) disease favors the direct development of infective larvae of Strongyloides stercoralis, which may facilitate hyperinfection and, hence, disseminated strongyloidiasis. To do this, we sought correlations between the immune status of the subjects and the development of S. stercoralis infections. Among 35 adults, there were significant negative rank correlations between CD4+ cell counts and the proportions of free-living male and female worms. Thus, in individuals with preserved immune function, direct development of S. stercoralis is favored, whereas, in individuals with lesser immune function, indirect development is relatively more common. These results may explain the notable absence of disseminated strongyloidiasis in advanced HIV disease. Because disseminated infection requires the direct development of infective larvae in the gut, the observed favoring of indirect development in individuals immunosuppressed by advancing HIV disease is not consistent with the promotion of disseminated infection.

The effect of the host immune response on the parasitic nematode Strongyloides ratti

The host immune response has profound effects on parasitic nematode infections. Here we have investigated how a range of infection parameters are affected by host immune responses and by their suppression and enhancement. The infection parameters considered were the number of parasitic females, their size, per capita fecundity and intestinal position. We found that in immunosuppressive treatments worms persist in the gut, sometimes with a greater per capita fecundity, maintain their size and have a more anterior gut position, compared with worms from control animals. In immunization treatments there are fewer worms in the gut, sometimes with a lower per capita fecundity and they are shorter and have a more posterior gut position, compared with worms from control animals. Worms from animals immunosuppressed by corticosteroid treatment reverse their changes in size and gut position. This description of these phenomena pave the way for a molecular biological analysis of how these changes in infection parameters are brought about by the host immune response.

Variation in Caenorhabditis elegans dauer larva formation

Dauer larvae of Caenorhabditis elegans are formed when young larvae experience conditions of low food availability and high conspecific population density; non‐dauer, third stage larvae are formed in conditions of plenty. This developmental response to environmental conditions is an example of phenotypic plasticity; that is, an environmentally induced change in phenotype and, as such, a manifestation of a genotype–environment interaction. Extensive variation was found in reaction norms of phenotypic plasticity of dauer formation among wild lines of C. elegans. Recombinant‐inbred lines were constructed from parental lines with very different reaction norms of dauer formation. These recombinant‐inbred lines had a wide range of reaction norms, of a range greater than that set by the parental lines. The natural variation in reaction norms of dauer formation in C. elegans is, presumably, an adaptation to enhance fitness under the lines different natural prevailing conditions. The genetic basis of this variation, as well as its phenotypic consequences, are now ripe for further investigation.

A study of the cells in the explanted viable cryopreserved allograft valve.

From June 1975 to December 1987, 231 patients underwent aortic valve replacement with a viable cryopreserved allograft aortic valve. Throughout this era, a uniform procurement and preservation was used to maintain leaflet fibroblast viability. The allograft valve was obtained from coronors autopsies within 24 hours of death, and more recently from organ donors, incubated for 24 hours in low dose antibiotic solution followed immediately by cryopreservation (mean time interval 39 hours after donor death). Viability was ensured by monitoring glucose utilization of the aortic and pulmonary valves and by demonstrating fibroblast growth in tissue cultured from the pulmonary valve. A uniform protocol for valve preparation was used during the entire experience.

Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis.

Summary The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.

Extraordinary plasticity in aging in Strongyloides ratti implies a gene-regulatory mechanism of lifespan evolution.

Aging evolves as the result of weakened selection against late‐acting deleterious alleles due, for example, to extrinsic mortality. Comparative studies of aging support this evolutionary theory, but details of the genetic mechanisms by which lifespan evolves remain unclear. We have studied aging in an unusual nematode, Strongyloides ratti, to gain insight into the nature of these mechanisms, in this first detailed examination of aging in a parasitic nematode. S. ratti has distinct parasitic and free‐living adults, living in the rat small intestine and the soil, respectively. We have observed reproductive and demographic aging in parasitic adults, with a maximum lifespan of 403 days. By contrast the maximum lifespan of free‐living adults is only 5 days. Thus, the two adults of S. ratti have evolved strikingly different rates of aging. Parasitic nematode species are frequently longer‐lived than free‐living species, presumably reflecting different extrinsic mortality rates in their respective niches. Parasitic and free‐living female S. ratti are morphologically different, yet genetically identical. Thus, the 80‐fold difference in their lifespans, the greatest plasticity in aging yet reported, must largely reflect evolved differences in gene expression. This suggests that interspecific differences in lifespan may evolve via similar mechanisms.

Diurnal cortisol patterns are associated with physical performance in the Caerphilly Prospective Study

Background Cross-sectional studies have suggested that elevated cortisol is associated with worse physical performance, a surrogate of ageing. We examined the relationship between repeat cortisol measures over 20 years and physical performance in later life. Methods Middle-aged men (45–59 years) were recruited between 1979 and 1983 (Phase 1) from the Caerphilly Prospective Study (CaPS) and re-examined 20 years later at 65–83 years of age (Phase 5). Participants included 750 and 898 subjects with either Phase 1 and/or Phase 5 data on exposure and outcomes. Outcome measures were walking speed and balance time and exposures included morning fasting serum cortisol (Phase 1) and four salivary samples on 2 consecutive days (Phase 5). Results Faster walking speed was associated with higher morning cortisol at Phase 1 [coefficient per standard deviation (SD) increase 0.68, 95% confidence interval (95% CI) 0.09–1.27; Pu2009=u20090.02] though this was attenuated after adjustment for covariates (coefficient per SD increase 0.45; 95% CI –0.16 to 1.07; Pu2009=u20090.15). Higher night-time cortisol at Phase 5 was associated with slower speed (coefficient per SD increase –1.06; 95% CI –1.60 to –0.52; Pu2009<u20090.001) and poorer balance (odds ratio of top tertile vs bottom 2.49; 95% CI 1.63–3.81; Pu2009<u20090.001). Worst performance was seen for men with a poor morning response (Phase 1) and less nocturnal decline (Phase 5). Conclusions Dysregulation of the hypothalamic pituitary adrenal (HPA) axis is associated with worse physical performance in later life. This may reflect a causal effect of the HPA axis on ageing or that ageing itself is associated with reduced HPA reactivity.