Somatotrope GHRH/GH/IGF-1 axis at the crossroads between immunosenescence and frailty.

Immunosenescence, characterized by complex modifications of immunity with age, could be related to frailty syndrome in elderly individuals, leading to an inadequate response to minimal aggression. Functional decline (i.e., the loss of ability to perform activities of daily living) is related to frailty and decreased physiological reserves and is a frequent outcome of hospitalization in older patients. Links between immunosenescence and frailty have been explored and 20 immunological parameters, including insulin-like growth factor-1 (IGF-1), thymopoeisis, and telomere length, were shown to be affected in elderly patients with functional decline. A strong relationship between IGF-1 and thymic ouput was evidenced. IGF-1, a mediator of growth hormone (GH), was subsequently shown to induce interleukin-7 secretion in cultured primary human thymic epithelial cells. We are exploring the stress hypothesis in which an acute stressor is used as the discriminator of frailty susceptibility. GH can counteract the deleterious immunosuppressive effects of stress-induced steroids. Under nonstress conditions, the immunosenescent system preserves physiological responses, while under stress conditions, the combination of immunosenescence and a defect in the somatotrope axis might lead to functional decline.

[Do the structure and functioning of the elderly's social network influence functional health: a preliminary study]. / La santé fonctionnelle des aînés est-elle influencée par la structure et le fonctionnement de leur réseau social : étude exploratoire.

We examined structural and functional characteristics of social networks related to health and well-being among community-dwelling older adults. A survey was performed in Brussels, using an original name-generating network inventory, to explore the structure and types of social ties (e.g. children, friends, neighbors) which forms the elderly's network. Different kinds of support (instrumental, emotional, social) were assessed due to the multiple contents of social exchanges between the elderly and their network's members. Our results highlighted some important social network resources. Especially, social participation, contacts with friends of the same age and reciprocity of social relationships are likely to promote functional health and well-being in later life. We discuss our findings in relation to major social network's typologies referring to older adults.

Changes in the clinical features of older patients admitted from the emergency department.

Demographic changes and healthcare reforms may impact the profile of hospitalized older persons. In this study, we sought to compare the characteristics of two prospective cohorts recruited at a ten-year interval (1999, n=253-2009, n=355). They included older patients (≥75 years) admitted through the emergency department for at least 48 h in acute non-geriatric wards in the same university hospital. The exclusion criteria were patients who were admitted directly to the intensive care unit, who were dependent for all 6 Activities of Daily Living (ADL), who had recently suffered from a major stroke, or whose with a life expectancy of less than 3 months. Median age was higher in 2009 than in 1999 (83 vs. 81; p=0.020), with a higher proportion of those aged 85 years and over (p=0.026). Patients in the 2009 cohort were less likely to live in a nursing home (p=0.018), more dependent for the basic ADL (p<0.001), more independent for the instrumental ADL (p<0.001). They were more likely to have fallen in the previous year (p<0.001). They took more medications (p<0.001). Their length-of-stay was shorter (p<0.001), but they were more likely to be discharged to a rehabilitation center (p<0.001). They underwent more early re-admissions (p=0.020) and similar 3-month functional decline (p=0.614). In conclusion, within a decade, the social, functional and medical characteristics of older patients admitted to hospital have changed significantly. In view of the high consumption of in-patient services by this population, hospitals must adapt to these rapid changes.

The prevalence of sarcopenia in very old individuals according to the European consensus definition: insights from the BELFRAIL study.

BACKGROUND: the prevalence of sarcopenia varies widely between studies. The objective of this study was to assess the prevalence of sarcopenia in a representative sample of persons aged 80 years and older according to the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm and the proposed cut-off values. A secondary aim was to investigate the relationship between different individual criteria and low physical performance capacity. METHODS: baseline data of the prospective BELFRAIL study (BFC80+) were analysed. Sarcopenia status was determined according to the EWGSOP guidelines. The skeletal muscle mass index (SMI) was assessed according to bioelectrical impedance. Muscle strength and muscle performance were evaluated according to grip strength and the modified short physical performance battery (SPPBm). A logistic regression analysis was performed. RESULTS: according to the EWGSOP algorithm, 12.5% of the participants were classified in the sarcopenia group. Sixty percent of the female participants had muscle strength values below the cut-off and 70% had low SPPBm values. In males, these prevalence values were 49.5% for grip strength and 39.7% for SPPB. The logistic regression analysis showed that low SPPBm was associated with grip strength (OR: 0.88, 95% CI: 0.84-0.92) independent of SMI. CONCLUSION: in a population-based sample of the very old the prevalence of sarcopenia according to the EWGSOP algorithm is similar to the prevalence of sarcopenia with SMI as a single criterion. A large number of participants with a sufficient SMI value showed low muscle strength and/or a poor SPPBm score. A low SPPBm was associated with grip strength but not with SMI.

Health outcomes of older patients colonized by multi-drug resistant bacteria (MDRB): a one-year follow-up study.

The objective of this study was to examine whether asymptomatic colonization with MDRB would affect outcomes in older patients one year after hospitalization in a geriatric ward. Patient samples were analyzed to identify specific MDRBs, including methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing Enterobaceriaceae (ESBLE), and vancomycin-resistant enterococci (VRE). Among 337 patients screened at hospital admission, 62 (18%) carried one or more MDRB isolates (MRSA: n=23; ESBLE: n=39; VRE: n=2). At 12 months after admission, 320 patients were interviewed by telephone (17 patients lost to follow up) to assess all-cause mortality, nursing home admissions, functional decline, and hospital readmissions. All-cause mortality rates were similar in MDRB carriers (34%; n=61) and non-carriers (30%; n=259) (P=0.512). Nursing home admission, functional decline, and hospital readmission did not differ between the two groups. In this population, predictors of mortality were: male gender (P=0.002), cognitive disorders at admission (P=0.028), low pre-albumin level at admission (P=0.048), a high level of co-morbidities (P=0.002), and a history of an acute condition in the three months prior to initial hospital admission (P=0.024). In conclusion, in this cohort of older patients, asymptomatic MDRB colonization was not significantly associated with adverse health outcomes at a one-year follow-up after hospitalization. The potential limitations of the study were the small sample size, relatively high mortality rate, and lack of MDRB reassessment during the follow-up.

[The Get-up early test, elaboration process of a new screening tool for psychomotor disadaptation syndrome]. / Élaboration d'un test de dépistage du syndrome de désadaptation psychomotrice : le Get-up early test.

Major features of the psychomotor disadaptation syndrome (SDPM) include motor skill dysfunctions with alteration of postural capabilities, walking abilities and psychomotric automatisms. Mini motor test (TMM) is the gold standard used by skilled physiotherapists in order to assess the syndrome. The aim of this article is to present the elaboration process of a new SDPM screening tool, called the Get-up early test. The test was firstly elaborated through consensus of nine experts in the geriatric field. This first 5-items version had poor inter-rater reproducibility and was therefore modified in a new 4-item version. This new version had substantial inter-rater concordance. Compared to the TMM as gold standard, in two different settings (acute ward and nursing home), with a cut-off value≥1/4, diagnostic performance was good (sensibility: 0.73 and specificity 0.88; area under curve: 0.823). The last step was to implement the screening tool in three Mobile geriatric units and we report here their experience. The Get-up early test may be suggested as a new screening tool in order to detect SDPM before more in-depth comprehensive geriatric assessment, and to early adapt the care plan.

Multidrug-resistant bacteria colonization amongst patients newly admitted to a geriatric unit: a prospective cohort study.

OBJECTIVES: To determine prevalence, incidence and risk factors of colonization by extended-spectrum ß-lactamase-producing Enterobacteriacae (ESBLE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) in aged subjects admitted to an acute geriatric unit at a teaching hospital. METHODS: During 12 months, 337 patients were screened by nasal, oropharyngeal, groin, axillary and rectal swabs upon admission and at discharge. RESULTS: The prevalence of ESBLE, MRSA and VRE carriage upon admission was 11.6%, 7.5% and 0.6%, respectively. The incidence density of ESBLE and MRSA carriage was respectively of 1.77 and 2.40 new cases for 1000 patient-days. No cases of VRE acquisition were found. Risk factors for ESBLE colonization on admission were: multiple contacts with the hospital within the previous year, chronic catheter use and a high level of dependency. For MRSA, risk factors were: chronic wounds, anti-acid use and a high level of dependency. CONCLUSION: This study shows a high prevalence of asymptomatic colonization of ESBL-producing Escherichia coli in patients admitted to an acute geriatric ward, as high as MRSA carriage. A low functional status is a common risk factor both for ESBLE and for MRSA colonization and it highlights the need to reinforce infection control measures.

Transcriptomic biomarkers of the response of hospitalized geriatric patients admitted with heart failure. Comparison to hospitalized geriatric patients with infectious diseases or hip fracture.

The abundance of a preselection of transcripts involved in inflammation, immunosenescence and stress response was compared between PBMC of healthy aged donors and aged patients in acute phase of heart failure and at recovery. This study identified 22 transcripts differentially abundant in acute phase of heart failure versus healthy aged subjects. Transcripts involved in inflammation and oxidative stress were more abundant. Those associated with T-cell functions were less abundant. The results were compared to two other major acute geriatric issues: infectious diseases and hip fracture. In acute phase, compared to healthy aged subjects, the abundance of 15/22 transcripts was also altered in both geriatric infectious diseases and hip fracture. Many variations had not vanished at the recovery phase. The abundance of CD28, CD69, LCK, HMOX1, TNFRSF1A transcripts, known to be altered in healthy aged versus healthy young subjects, was further affected in acute phase of the three geriatric diseases considered. The transcript levels of BCL2, CASP8, CCL5, DDIT3, EGR3, IL10RB, IL1R2, SERPINB2 and TIMP1 were affected in all three pathological conditions compared to healthy aged, but not versus healthy young subjects. In conclusion, this work provides critical targets for therapeutic research on geriatric heart failure, infectious diseases and hip fracture.

Clinical profiles of patients colonized or infected with extended-spectrum beta-lactamase producing Enterobacteriaceae isolates: a 20 month retrospective study at a Belgian University Hospital.

BACKGROUND: Description of the clinical pictures of patients colonized or infected by ESBL-producing Enterobacteriaceae isolates and admitted to hospital are rather scarce in Europe. However, a better delineation of the clinical patterns associated with the carriage of ESBL-producing isolates may allow healthcare providers to identify more rapidly at risk patients. This matter is of particular concern because of the growing proportion of ESBL-producing Enterobacteriaceae species isolates worldwide. METHODS: We undertook a descriptive analysis of 114 consecutive patients in whom ESBL-producing Enterobacteriaceae isolates were collected from clinical specimens over a 20-month period. Clinical data were obtained through retrospective analysis of medical record charts. Microbiological cultures were carried out by standard laboratory methods. RESULTS: The proportion of ESBL-producing Enterobacteriaceae strains after exclusion of duplicate isolates was 4.5% and the incidence rate was 4.3 cases/1000 patients admitted. Healthcare-associated acquisition was important (n = 104) while community-acquisition was less frequently found (n = 10). Among the former group, two-thirds of the patients were aged over 65 years and 24% of these were living in nursing homes. Sixty-eight (65%) of the patients with healthcare-associated ESBL, were considered clinically infected. In this group, the number and severity of co-morbidities was high, particularly including diabetes mellitus and chronic renal insufficiency. Other known risk factors for ESBL colonization or infection such as prior antibiotic exposure, urinary catheter or previous hospitalisation were also often found. The four main diagnostic categories were: urinary tract infections, lower respiratory tract infections, septicaemia and intra-abdominal infections. For hospitalized patients, the median hospital length of stay was 23 days and the average mortality rate during hospitalization was 13% (Confidence Interval 95%: 7-19). Escherichia coli, by far, accounted as the most common ESBL-producing Enterobacteriaceae species (77/114; [68%]) while CTX-M-1 group was by far the most prevalent ESBL enzyme (n = 56). CONCLUSION: In this retrospective study, the clinical profiles of patients carrying healthcare-associated ESBL-producing Enterobacteriacae is characterized by a high prevalence rate of several major co-morbidities and potential known risk factors. Both, the length of hospital stay and overall hospital mortality rates were particularly high. A prospective case-control matched study should be designed and performed in order to control for possible inclusion bias.

Serum IL-6 and IGF-1 improve clinical prediction of functional decline after hospitalization in older patients.

BACKGROUND AND AIMS: Although inflammatory and hormonal markers have been associated with further functional adverse outcomes in community- dwelling seniors, these markers have not been studied from this perspective in acutely ill older patients. This prospective study was designed to determine whether biological markers can improve the predictive value of a clinical screening tool to assess the risk of functional decline in hospitalized older patients. METHODS: Patients aged 75 years and over admitted for hip fracture, acute heart failure or infection (n=118) were recruited. The clinical screening tool SHERPA was filled in on admission, with concomitant measurement of interleukin-6 (IL-6), insulin-like growth factor 1 (IGF-1), C-reactive protein (CRP), white blood cells, urea, albumin, pre-albumin and total cholesterol. Functional decline was defined as a decrease of one point in the activities of daily living scale between pre-admission and 3-month post-discharge status. We compared the discrimination calibration of SHERPA vs SHERPA+, a logistic regression model including SHERPA and selected biomarkers. RESULTS: Three months after discharge, functional decline had occurred in 46 patients. IL-6 and IGF-1 were selected, since their levels were significantly different between decliners and non-decliners, and were included in the new logistic regression model SHERPA+. Areas under the ROC curve [95% CI] for functional decline prediction were 0.73 [0.63-0.81] for SHERPA vs 0.79 [0.69-0.86] for SHERPA+ (p=0.14). However, SHERPA+ was better calibrated, as the average predicted risk of functional decline within subgroups matched the proportion which actually underwent functional decline (Brier score=0.185). Since functional decline was higher in patients with hip fracture, the SHERPA+ model was challenged by including the diagnosis. Only SHERPA, IGF-1 and diagnosis were significantly associated with functional decline. CONCLUSIONS: Selected biological markers may marginally improve the clinical prediction of post-discharge functional decline in hospitalized patients, and may allow to stratify them appropriately. The predictive value of these biomarkers is not fully independent of disease status. Further studies are needed to confirm these results in a cohort representative of older patients admitted through the emergency department.

Differentially abundant transcripts in PBMC of hospitalized geriatric patients with hip fracture compared to healthy aged controls.

The abundance of a selection of transcript species involved in inflammation, immunosenescence and stress response was compared between PBMC of 35 geriatric patients with hip fracture in acute phase (days 2-4 after hospitalization) or convalescence phase (days 7-10) and 28 healthy aged controls. Twenty-nine differentially abundant transcripts were identified in acute phase versus healthy ageing. Twelve of these transcripts remained differentially abundant in convalescence phase, and 22 were similarly differentially abundant in acute phase of geriatric infectious diseases. Seven of these 22 transcripts were previously identified as differentially abundant in PBMC of healthy aged versus healthy young controls, with further alteration for CD28, CD69, LCK, CTSD, HMOX1, and TNFRSF1A in acute phase after geriatric hip fracture and infectious diseases. The next question is whether these alterations are common to other geriatric diseases and/or preexist before the clinical onset of the diseases.

Transcriptomic biomarkers of the response of hospitalized geriatric patients with infectious diseases.

BACKGROUND: Infectious diseases are significant causes of morbidity and mortality among elderly populations. However, the relationship between oxidative stress, immune function and inflammatory response in acute phase of the infectious disease is poorly understood. RESULTS: Herein the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of 28 healthy aged probands and 39 aged patients in acute phase of infectious disease (day 2-4 after hospitalization) or in convalescence phase (day 7-10). This study provides a list of 24 differentially abundant transcript species in the acute phase versus healthy aged. For instance, transcripts associated with inflammatory and anti-inflammatory reactions (TNFRSF1A, IL1R1, IL1R2, IL10RB) and with oxidative stress (HMOX1, GPX1, SOD2, PRDX6) were more abundant while those associated with T-cell functions (CD28, CD69, LCK) were less abundant in acute phase. The abundance of seven of these transcripts (CD28, CD69, LCK, CTSD, HMOX1, TNFRSF1A and PRDX6) was already known to be altered in healthy aged probands compared to healthy young ones and was further affected in aged patients in acute phase, compromising an efficient response. CONCLUSION: This work provides insights of the state of acute phase response to infections in elderly patients and could explain further the lack of appropriate response in the elderly compared to younger persons.

Transcriptomic biomarkers of human ageing in peripheral blood mononuclear cell total RNA.

Age-related changes of gene expression contribute to the physiological alteration observed with human ageing. Herein, the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of healthy young to middle-age probands (35.0 +/- 6.5 year old) and healthy old probands (82.5 +/- 6.8 year old). This study provides a list of 16 differentially abundant transcripts species in the healthy old probands. Thus, these changes of abundance can be considered as easily accessible biomarkers of ageing. Some of these differential abundances like CD28, CD69, LCK (decreased abundance in old subjects), CD86, Cathepsin D, H and S (increased abundance in old subjects) might explain biochemical and cytochemical changes observed at the protein level in the immune system and thus might correspond to regulatory processes affecting the ageing process. Indeed these changes reflect the low-grade pro-inflammatory status observed in old persons and suggest a hypo-responsiveness of T-cells together with an increase in antigen presentation potential. In addition, among the differentially abundant transcripts were transcripts involved in the oxidative stress response HMOX1 and HSPA6 mRNAs were found as more abundant in PBMC from elderly subjects.

Caring, employment and health among adults of working age: evidence from Britain and Belgium.

BACKGROUND: For those of working age, results are inconclusive when exploring the health impact of providing care. Moreover, population data is lacking and the impact of welfare policies on the caregivers' health has not been yet analysed. METHODS: Associations between general health and care giving, adjusting for differences in employment and socio-economic position, were explored for working age adults using logistic regression models. Data came from the 2001 British census (n = 1,361,222, 5% sample) and from the 2001 Belgian census (n = 4,368,637). The final model was stratified by employment status, given the significant interaction between caregiving and employment status. RESULTS: In both countries, when compared with those providing no care, men and women providing >or=20 h of care per week had an increased risk of poor health. This increased risk was attenuated after adjustment for socio-economic position and particularly after adjustment for differences in employment status. However after stratifying by employment status, a dose response relationship between time spent caring and poor health was observed for the employed and unemployed, but not for the economically inactive. CONCLUSIONS: Despite contrasting welfare systems, employment status plays an important role in the association between caring and health in both countries. For the economically active, providing more care increases the risk of poor health. Whilst formal employment may be good for general health, having to informally care whilst in formal employment may have a detrimental health impact.

Combined effects of functionally-oriented exercise regimens and nutritional supplementation on both the institutionalised and free-living frail elderly (double-blind, randomised clinical trial).

BACKGROUND: Consistently swelling proportion of the frail elderly within a modern society challenges the overstrained public health sector to provide both adequate medical care and comprehensive assistance in their multiple functional deficits of daily living. Easy-to-apply and task-specific ways of addressing this issue are being sought out, with a view to proposing systemic solutions for nationwide application. METHODS: The present randomised, double-blind, placebo-controlled, 7-week clinical trial aimed to determine whether specifically structured, intensive exercise regimens, combined with nutritional supplementation, might improve and help sustain individual muscle strength and mobility, and possibly enhance individual functional capabilities in an on-going quest for active prevention of care-dependency. Ninety-one frail elderly (F 71 M 20; mean age 79 years) were recruited from both nursing home residents and community dwellers and randomly split into four groups: Group I - progressive resistance exercises (PRE) + functionally-oriented exercises (FOE) + nutritional supplementation (NS), Group II - PRE + FOE + placebo, Group III--standard exercises (SE) + FOE + NS, Group IV - SE + FOE + placebo. Each group pursued a 45 min. exercise session 5 times weekly. The subjects' strength with regard to four muscle groups, i.e. hip and knee extensors and flexons, was assessed at 80% (1 RM) weekly, whereas their balance and mobility at baseline and at the end of the study. RESULTS: The study was completed by 80 subjects. Despite its relatively short duration significant differences in muscle strength were noted both in Group I and Group II (p = 0.01; p = 0.04; respectively), although this did not translate directly into perceptible improvement in individual mobility. Notable improvements in individual mobility were reported in Group III and Group IV (p = 0.002), although without positive impact on individual muscle strength. CONCLUSION: Comprehensively structured, high-intensity regimen made up of diverse exercise types, i.e. functionally-oriented, progressive resistance and standard ones, preferably if combined with nutritional supplementation in adequate volume, demonstrates clear potential for appreciably improving overall functional status in the frail elderly in terms of individual walking capacity and muscle strength. TRIAL REGISTRATION: Central Register of Clinical Trials, Poland--CEBK180/2000.

Appropriate prescribing in elderly people: how well can it be measured and optimised?

Prescription of medicines is a fundamental component of the care of elderly people, and optimisation of drug prescribing for this group of patients has become an important public-health issue worldwide. Several characteristics of ageing and geriatric medicine affect medication prescribing for elderly people and render the selection of appropriate pharmacotherapy a challenging and complex process. In the first paper in this series we aim to define and categorise appropriate prescribing in elderly people, critically review the instruments that are available to measure it and discuss their predictive validity, critically review recent randomised controlled intervention studies that assessed the effect of optimisation strategies on the appropriateness of prescribing in elderly people, and suggest directions for future research and practice.

Effect of a collaborative approach on the quality of prescribing for geriatric inpatients: a randomized, controlled trial.

OBJECTIVES: To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management (GEM) care on the appropriateness of prescribing. DESIGN: Randomized, controlled trial, with the patient as unit of randomization. SETTING: Acute GEM unit. PARTICIPANTS: Two hundred three patients aged 70 and older. INTERVENTION: Pharmaceutical care provided from admission to discharge by a specialist clinical pharmacist who had direct contacts with the GEM team and patients. MEASUREMENTS: Appropriateness of prescribing on admission, at discharge, and 3 months after discharge, using the Medication Appropriateness Index (MAI), Beers criteria, and Assessing Care of Vulnerable Elders (ACOVE) underuse criteria and mortality, readmission, and emergency visits up to 12 months after discharge. RESULTS: Intervention patients were significantly more likely than control patients to have an improvement in the MAI and in the ACOVE underuse criteria from admission to discharge (odds ratio (OR)=9.1, 95% confidence interval (CI)=4.2-21.6 and OR=6.1, 95% CI=2.2-17.0, respectively). The control and intervention groups had comparable improvements in the Beers criteria. CONCLUSION: Pharmaceutical care provided in the context of acute GEM care improved the appropriate use of medicines during the hospital stay and after discharge. This is an important finding, because only limited data exist on the effect of various strategies to improve medication use in elderly inpatients. The present approach has the potential to minimize risk and improve patient outcomes.