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Background: Hypoglycemia, especially at old age, can lead to several major problems, such as falls and cognitive deficits. The aim of our study was to detect hypoglycemia in older persons with and without diabetes mellitus type 2 (T2DM).Methods: The frequency and duration of hypoglycemia/hyperglycemia was studied in ambulatory geriatric (>75 years), non-diabetic persons (Group 1, n=10), using real time Continuous Glucose Monitoring (CGM, Dexcom G6), and in age- and sex-matched cognitively-healthy, T2DM patients having HbA1c levels < 9.0% (Group 2, n=10). The device was used during 20 days per person, who was blinded for the values on the receiver (except in case of severe hypo- or hyperglycemia). Data were stored for further analysis on the Dexcom Clarity Portal.Results: Hypoglycemia occurred frequently in older persons without T2DM, despite absence of hypoglycemia-inducing medication. In this group, people had 0.50% (median value) of the time glycemic values below 70 mg/dL, most of the episodes happened during nighttime. Conclusions: Our study demonstrates that hypoglycemia occurs frequently in non-diabetic older persons. Further studies are needed to determine whether this could be part of the normal aging process, and to determine if hypoglycemia might contribute to cognitive deterioration.

One of the most debilitating consequences of aging is the progressive decline in immune function, known as immunosenescence. This phenomenon is characterized by a shift in T-cell pheno-types, with a manifest decrease of naive T-cells—dealing with newly encountered antigens—and a concomitant accumulation of senescent and regulatory T-cells, leading to a greater risk of morbidity and mortality in older subjects. Additionally, with aging, several studies have unequivocally revealed an increase in the prevalence of onchocerciasis infection. Most lymphatic complications, skin and eye lesions due to onchocerciasis are more frequent among the elderly population. While the reasons for increased susceptibility to onchocerciasis with age are likely to be multi-factorial, age-associated immune dysfunction could play a key role in the onset and progression of the disease. On the other hand, there is a growing consensus that infection with onchocerciasis may evoke deleterious effects on the host’s immunity and exacerbate immune dysfunction. Indeed, Onchocerca volvulus has been reported to counteract the immune responses of the host through molecular mimicry by impairing T-cell activation and interfering with the processing of antigens. Moreover, reports indicate impaired cellular and humoral immune responses even to non-parasite antigens in onchocerciasis patients. This diminished protective response may intensify the immunosenescence outcomes, with a consequent vulnerability of those affected to additional diseases. Taken together, this review is aimed at contributing to a better understanding of the immunological and potential pathological mechanisms of onchocerciasis in the older population., SCOPUS: re.j, info:eu-repo/semantics/published

Background Orthostatic hypotension (OH) in geriatric patients frequently involves a component of autonomic failure (AF). The combination of OH with nocturnal hypertension (NHT) is indicative of AF, which is described as pure (PAF), when neurologic symptoms are absent, or as multisystem atrophy (MSA), when combined with motor disturbance (Parkinsonism or Parkinson disease). Case presentation An 87-year-old man presented with long-lasting OH. He frequently fell, causing several fractures, and he developed heart failure. Blood pressure (BP) registration revealed a reversal of the day-night rhythm with NHT. An 18-FDG PET brain CT scan showed cerebellar hypometabolism, indicating MSA. Conclusions This case demonstrates the use of continuous BP registration in geriatric patients with OH for diagnosing NHT. It illustrates the usefulness of 18-FDG PET brain CT scan to specify the nature of the AF. The case also illustrates the difficulty of managing the combination of OH and NHT.

OBJECTIVES: Antihypertensive drugs (AHTD) and statins have been shown to have effects beyond their primarily designed purpose; here we investigate their possible effect on muscle performance and strength in older adults following a physical exercise programme. DESIGN: The Senior PRoject INtensive Training (SPRINT) study is a randomised, controlled clinical trial designed to evaluate the effects of physical exercise on the immune system and muscle performance in older adults. PARTICIPANTS: In this secondary analysis, we included 179 independent participants (aged 65 years and above). We applied further categorisation based on medication use: AHTD (including, angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARB], β-blockers, and other AHTD) and statins. INTERVENTION: Participants were allocated randomly to one of the three exercise protocols: intensive strength training 3 times/week (3 × 10 repetitions at 80% of one-repetition maximum), strength endurance training (2 × 30 repetitions at 40% of one-repetition maximum), or control (passive stretching exercise) for 6 weeks. MEASUREMENTS: The change in maximal hand grip strength (GS), muscle fatigue resistance (FR), Muscle Strength Index (MSI), the 6-min walk test (6MWT), and Timed Up and Go Test (TUG) were assessed before and after 6 weeks of training. RESULTS: After 6 weeks, muscle strength (MSI and TUG) improved significantly in all training groups compared to baseline, independently of AHTD use. Moreover, AHTD had no effect on exercise improvements, with no significant differences between medication groups, except for TUG in ARB users, which exhibited a significantly lower performance. On the other hand, statin users presented a significantly longer FR time, indicating better performance compared to non-users. Finally, medication did not affect the participants' commitment to the training programme. CONCLUSION: Our study showed that statins and ARB usage might affect participant's response to strength training. Nevertheless, 6 weeks of training significantly improved muscle strength and performance irrespective of AHTD or statin use.

Heat shock proteins (HSPs) play an essential role in protecting proteins from denaturation and are implicated in diverse pathophysiological conditions like cardiovascular diseases, cancer, infections, and neurodegenerative diseases. Scientific evidence indicates that if HSP expression falls below a certain level, cells become sensitive to oxidative damage that accelerates protein aggregation diseases. On the other hand, persistently enhanced levels of HSP can lead to inflammatory and oncogenic changes. To date, although techniques for measuring HSPs exist, these assays are limited for use in specific sample types or are time consuming. Therefore, in the present study, we developed a single-molecule assay digital ELISA technology (Single Molecule Array—SIMOA) for the measurement of HSPs, which is time effective and can be adapted to measure multiple analytes simultaneously from a single sample. This technique combines two distinct HSP-specific antibodies that recognize different epitopes on the HSP molecule. A recombinant human HSP protein was used as the standard material. The assay performance characteristics were evaluated by repeated testing of samples spiked with HSP peptide at different levels. The limit of detection was 0.16 and 2 ng/mL for HSP27 and HSP70, respectively. The inter- and intra-assay coefficients of variation were less than 20% in all tested conditions for both HSPs. The HSP levels assayed after serial dilution of samples portrayed dilutional linearity (on average 109%, R2 = 0.998, p < 0.001, for HSP27 and 93%, R2 = 0.994, p < 0.001, for HSP70). A high linear response was also demonstrated with admixtures of plasma exhibiting relatively very low and high levels of HSP70 (R2 = 0.982, p < 0.001). Analyte spike recovery varied between 57% and 95%. Moreover, the relative HSP values obtained using Western blotting correlated significantly with HSP values obtained with the newly developed SIMOA assay (r = 0.815, p < 0.001 and r = 0,895, p < 0.001 for HSP70 and HSP27, respectively), indicating that our method is reliable. In conclusion, the assay demonstrates analytical performance for the accurate assessment of HSPs in various sample types and offers the advantage of a huge range of dilution linearity, indicating that samples with HSP concentration highly above the calibration range can be diluted into range without affecting the precision of the assay.

Ageing is characterized by a low-grade chronic inflammation marked by elevated circulating levels of inflammatory mediators. This chronic inflammation occurring in the absence of obvious infection has been coined as inflammageing and represents a risk factor for morbidity and mortality in the geriatric population. Also, with ageing, important perturbations in the gut microbiota have been underlined and a growing body of literature has implicated age-related gut dysbiosis as contributing to a global inflammatory state in the elderly. Notwithstanding, very little attention has been given to how gut microbiota impact inflammageing. Here, we investigate the available evidence regarding the association between inflammageing and gut microbiota during ageing. PubMed, Web of Science and Scopus were systematically screened, and seven relevant articles in animals or humans were retrieved. The animal studies reported that Parabacteroides, Mucispirillum, Clostridium and Sarcina positively associate with the pro-inflammatory MCP-1 while Akkermansia, Oscillospira, Blautia and Lactobacillus negatively correlate with MCP-1. Furthermore, "aged"-type microbiota were associated with increased levels of IL6, IL-10, Th1, Th2, Treg, TNF-α, TGF-β, p16, SAMHD1, Eotaxin, and RANTES; activation of TLR2, NF-κB and mTOR; and with decreased levels of cyclin E and CDK2. On the other hand, the study on humans demonstrated that bacteria of the phylum Proteobacteria exhibited a positive correlation with IL-6 and IL-8, while Ruminococcus lactaris et rel. portrayed a negative correlation with IL-8. We conclude that changes in "aged"-type gut microbiota are associated with inflammageing., info:eu-repo/semantics/published

Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76–83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition., SCOPUS: ar.j, info:eu-repo/semantics/published

The current serological test for human onchocerciasis relies on IgG4 reactivity against the parasite Ov-16 antigen, with reported sensitivities of only 60–80%. As control programs move from control to elimination, it is imperative to identify novel molecules that could improve the serodiagnosis reliability of this disease. In this study we compared the sensitivity of total IgG against OvMANE1—a chimeric antigen previously identified as a potential biomarker of human onchocerciasis—with that of an Ov-16 antibody test to detect an Onchocerca volvulus infection in persons presenting with microfilaria in skin snips. One hundred and ninety serum samples were obtained from persons with epilepsy in an onchocerciasis-endemic area at Ituri in the Democratic Republic of Congo where ivermectin has never been distributed. Fifty-nine (31.1%) samples were from individuals with a positive skin snip test; 41 (69.5%) of these 59 samples were positive with the OvMANE1 test and 41 (69.5%) with the Ov-16 test; 30 (50.8%) samples were positive for both tests and in 52 (88.1%) at least one of the tests was positive. Testing the 131 sera from persons with a negative skin snip result revealed that 63 (48.1%) were positive exclusively with the OvMANE1 test, 13 (9.9%) exclusively with the Ov-16 test and 25 (19.1%) with both tests. Nine European samples from individuals without past travel history in onchocerciasis endemic zones and 15 samples from Rwanda, a hypoendemic country for onchocerciasis were all negative for the OvMANE1 and Ov-16 tests. However, the specificity of both tests was difficult to determine due to the lack of a gold standard for antibody tests. In conclusion, the tandem use of OvMANE1 and Ov-16 tests improves the sensitivity of detecting Onchocerca volvulus seropositive individuals but, the OvMANE1 test needs to be further evaluated on samples from a population infected with other helminths to cautiously address its specificity.

Usual walking speed (WS) is a relatively easy and reproducible tool for detecting mobility impairment. For some reasons, however, geriatric patients might not be able to perform walking tests. Therefore, a subjective assessment could be an alternative method to screen for mobility impairment. In the present paper, we explore the use of the mobility item from the Mini Nutritional Assessment-short form (MNA-sf) to assess mobility and its congruence with walking speed in hospitalized and ambulatory patients. We analyzed retrospective data from 357 patients and found a highly significant correlation between WS and the MNA-sf mobility item. After dichotomization of the MNA-sf mobility score (mobility impairment ≤1 and no impairment >1), AUC for ROC curves showed that the mobility item derived from the MNA-sf reflects fairly well the mobility of geriatric hospitalized patients (AUC = 0.773), while it performs better in ambulatory patients (AUC = 0.838)., SCOPUS: ar.j, info:eu-repo/semantics/published

Background A chronic low-grade inflammatory profile (CLIP) is associated with sarcopenia in older adults. Protein and Vitamin (Vit)D have immune-modulatory potential, but evidence for effects of nutritional supplementation on CLIP is limited. Aim To investigate whether 13 weeks of nutritional supplementation of VitD and leucine-enriched whey protein affected CLIP in subjects enrolled in the PROVIDE-study, as a secondary analysis. Methods Sarcopenic adults (low skeletal muscle mass) aged ≥ 65 years with mobility limitations (Short Physical Performance Battery 4–9) and a body mass index of 20–30 kg/m2 were randomly allocated to two daily servings of active (n = 137, including 20 g of whey protein, 3 g of leucine and 800 IU VitD) or isocaloric control product (n = 151) for a double-blind period of 13 weeks. At baseline and after 13 weeks, circulating interleukin (IL)-8, IL-1 receptor antagonist (RA), soluble tumor-necrosis-factor receptor (sTNFR)1, IL-6, high-sensitivity C-reactive protein, pre-albumin and 25-hydroxyvitamin(OH)D were measured. Data-analysis included repeated measures analysis of covariance (corrected for dietary VitD intake) and linear regression. Results IL-6 and IL-1Ra serum levels showed overall increases after 13 weeks (p = 0.006 and p

Background Ageing-related low-grade inflammation is suggested to aggravate sarcopenia and frailty. This systematic review investigates the influence that drugs with anti-inflammatory effects (AIDs) have on inflammation and skeletal muscle. Methods PubMed and Web of Science were systematically screened for articles reporting the effects of AIDs on inflammation on one hand and on muscle mass and/or performance on the other. Results Twenty-eight articles were included. These articles were heterogeneous in terms of the subjects studied, intervention components, setting, and outcome measures. Articles on older humans with acute inflammation showed evidence that celecoxib and piroxicam could reduce inflammation and improve performance and that ibuprofen improves exercise-induced muscle hypertrophy and gains in strength. In younger humans, only the effects of AIDs combined with exercise were investigated; no significant benefits of non-selective COX-inhibitors were reported, but improved strength gains with etanercept and reduced muscle soreness with celecoxib were noted. Indomethacin increased acute exercise-induced inflammation and reduced satellite cell differentiation in exercising muscle. Most articles did not systematically report occurrences of side effects. Conclusions Although AIDs showed significant reduction in inflammation-induced muscle weakness in older hospitalised patients with acute inflammation, robust evidence is still lacking. When combined with exercise, AIDs presented a protective effect against age-related loss of muscle mass, thus enhancing muscle mass and performance. The mechanism regulating muscle strength and its mass seems to differ between individuals of old and young age. However, the effects seem drug-specific and dose-dependent and appear to be influenced by subjects' trainability and the clinical context. In addition, the balance between benefits and harm remains unclear.

Within the Active Ageing context (WHO), enhancing older peoples’ quality of life by focusing on their participation is essential. Although Active Ageing is relevant in nursing homes, the nursing home residents’ autonomy and participation on organizational level are often restricted. New ways to structurally enhance their participation must be found. This article discusses possible contributions of participatory action research as structural method in a new Active Ageing-envisioned nursing home, enabling residents’ participation and focuses on the practicalities of its implementation process. During an implementation project in the nursing home, participatory action research was introduced in the nursing home as weekly activity where residents assembled to observe the nursing home operation, identify problems and make suggestions for improvement. Based on the researchers’ experiences, implementing participatory action research needs a preparation and adaptation period for the nursing home staff, the participatory action research moderators and the residents to cope with the experienced challenges. Nevertheless, participatory action research appeared feasible and can bring added value to residents’ living conditions. This article contributes to the development of the participatory action research theory and the Active Ageing implementation in nursing home, since it shows the possibilities, challenges and assets of participatory action research towards a more frail population in the nursing home environment. Participatory action research might in turn lead to the realization of Active Ageing nursing home who endeavours to optimize residents’ quality of life.

Background: Inadequate nutritional intake and altered response of aging muscles to anabolic stimuli from nutrients contribute to the development of sarcopenia. Nutritional interventions show inconsistent results in sarcopenic older adults, which might be influenced by their basal nutritional status. Objective: To test if baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations and dietary protein intake influenced changes in muscle mass and function in older adults who received nutritional intervention. Methods and design: Post-hoc analysis was performed in the PROVIDE study that was a randomized controlled, double blind trial among 380 sarcopenic older adults. This study showed that those who received a vitamin D and leucine-enriched whey protein medical nutrition drink for 13 weeks gained more appendicular muscle mass (aMM), and improved lower-extremity function as assessed by the chair stand test compared with controls. To define low and high groups, a baseline serum concentration of 50 nmol/L 25(OH)D and baseline dietary protein intake of 1.0 g/kg/d were used as cut offs. Results: At baseline, participants with lower 25(OH)D concentrations showed lower muscle mass, strength and function compared with participants with a high 25(OH)D, while the group with lower protein intake (g/kg/day) had more muscle mass at baseline compared with the participants with higher protein intake. Participants with higher baseline 25(OH)D concentrations and dietary protein intake had, independent of other determinants, greater gain in appendicular muscle mass, skeletal muscle index (aMM/h(2)), and relative appendicular muscle mass (aMM/body weight x 100%) in response to the nutritional intervention. There was no effect modification of baseline 25(OH)D status or protein intake on change in chair-stand test. Conclusions: Sufficient baseline levels of 25(OH)D and protein intake may be required to increase muscle mass as a result of intervention with a vitamin D and protein supplement in sarcopenic older adults. This suggests that current cut-offs in the recommendations for vitamin D and protein intake could be considered the "minimum" for adults with sarcopenia to respond adequately to nutrition strategies aimed at attenuating muscle loss. (C) 2017 The Author(s). Published by Elsevier Ltd.

BACKGROUND AND PURPOSE:: Although physical activity (PA) is an important tool to counter osteoporosis, too few older patients with osteoporosis (OPWO) engage in PA. Little is known about specific motivators for and barriers to PA in OPWO, hindering the development of targeted PA promotion campaigns for these persons. Therefore, the main objective of this study was to identify motivators for and barriers to PA specifically in OPWO. METHODS:: This qualitative study identified specific motivators for and barriers to PA in OPWO through 2 different methods: focus groups with professionals and in-depth interviews with OPWO. RESULTS:: The OPWO tended to give a broad interpretation of what they considered as PA (practicing sports, physical work, and performing household activities), whereas the professionals seemed to mainly focus on (therapeutic) exercise as PA. Fifteen different motivators and 18 barriers have been identified. Among others, health improvement, social contact, habit, feeling good, and receiving medical advice from a medical doctor were motivators. Pain, fear of falling, bad weather, lack of interest, and caring for an ill partner were barriers to PA. For some older respondents, osteoporosis acted as a trigger for PA, and for others it was a barrier. CONCLUSIONS:: This study emphasizes the importance for health care professionals to give personalized PA advice regarding the nature and frequency of PA that is safe and beneficial for osteoporosis. It stands to reason that the information about PA needs to be clear and consistent. Furthermore, it is quintessential to mention that it can take some time to adapt to physical exercise and to experience the beneficial effects, because pain sensations during the first PA sessions can be perceived as barriers to OPWO. Misconceptions or barriers to PA should be countered by assessing motivators for and barriers to PA by the health care professional together with the older client so that barriers can be eliminated and motivators can be strengthened. Physical activity education should involve not only the OPWO but also their relatives, friends, and important peers. Different social aspects of PA and the encouragements from peers are stimulating for older adults to initiate and to continue PA. The results of our study can constitute a starting point for further research to identify the motivators for and barriers to PA with the highest impact on PA behavior in OPWO, thus enabling evidence-based PA promotion campaigns for this patient group. Language: en

Background:Mild cognitive impairment (MCI) is characterized by subjective and objective memory impairments in the absence of manifest functional decline. Mild changes in activities of daily living (ADL) can be present and probably predict conversion to dementia. A new advanced (a)-ADL tool was developed, evaluating high-level activities and, taking each participant as their own reference, distinguishing a global Disability Index (a-ADL-DI), a Cognitive Disability Index (a-ADL-CDI), and a Physical Disability Index (a-ADL-PDI), based on the number of activities performed and the severity and causes of the functional problem. This study evaluates the discriminative validity of the a-ADL in MCI.Method:Based upon clinical evaluation and a set of global, cognitive, mood, and functional assessments, 150 community-dwelling participants (average age 80.3 years (SD 5; 66–91)) were included and diagnosed as (1) cognitively healthy participants (n = 50); (2) patients with a-MCI (n = 48), or (3) mild to moderate AD (n = 52). The a-ADL tool was not a part of the clinical evaluation.Results:The a-ADL-DI and the a-ADL-CDI showed a sensitivity and specificity ranging from 70% to 94.2%, Positive Predictive Value ranging from 70% till 93.8%, and Negative Predictive Value from 64.4% and 93.8%, an area under the curve (AUC) ranging from 0.791 to 0.960. Functional decline related to physical deficits, as assessed by the a-ADL-PDI, did not discriminate between the different groups.Conclusion:The a-ADL tool has a good ability to distinguish normal and pathological cognitive aging. Its discriminative power for underlying causes of limitations may be an advantage.

BACKGROUND: Muscle fatigue, a prominent symptom in older patients, can be assessed by sustained maximal handgrip testing. The force decline during sustained maximal contraction is described for young adults, but data for elderly persons are scarce. The aim of this study was to investigate force-time characteristics during a sustained maximal handgrip effort according to age and clinical condition. METHODS AND MATERIALS: Force-time data were continuously recorded during sustained maximal grip effort in 91 elderly patients (aged 83±5years), 100 elderly controls (aged 74±5years) and 100 young controls (aged 23±3years). The force-time curve was divided in 4 parts per 25% strength drop observed. Time (representing fatigue resistance (FR)) was measured during which grip strength (GS) dropped to 75% (FR75), 50% (FR50), 25% (FR25) of its maximum and to exhaustion (FRexhaustion). Grip work ((GW), the area under the force-time curve) was measured for the 4 parts as well as for the first 20 and 30s of the fatigue protocol test. Strength decay (GWdecay), defined as the difference between the area under the curve (% GW) and a theoretical maximal area under the curve (assuming there's no strength drop), was also studied. In the elderly participants, relationships (controlling for age and sex) of GS, FR and GW with circulating IL-6 and TNF-α were analyzed. RESULTS: FRexhaustion was similar for all groups, whereas the duration of each of the 4 parts was significantly different between the 3 groups. FR75 was shortest in old patients (p=0.004), FR75-50 was almost twice as long in old community-dwelling compared to old patients and young controls (p

BACKGROUND: Literature reports on the effects of resistance training on heat shock protein70 (Hsp70) adaptation in older subjects are scarce. Moreover, the optimum training load required to obtain a beneficial adaptation profile is lacking. Therefore, the aim of this study was to determine the effects of resistance training at various external loads on extracellular Hsp70 (eHsp70) resting levels in older humans. METHODS: Fifty-six community-dwelling older (68±5years) volunteers were randomized to 12weeks of resistance training (3×/week) at either high-resistance (HIGH, 8 males, 10 females, 2×10-15 repetitions at 80% 1RM), low resistance (LOW, 9 Males, 10 Females, 1×80-100 repetitions at 20% 1RM), or mixed low resistance (LOW+, 9 Males, 10 Females, 1×60 repetitions at 20% 1RM followed by 1×10-20 repetitions at 40% 1RM). Serum was available from 48 out of the 56 participants at baseline and after 12weeks for determination of eHsp70. Mid-thigh muscle volume (computed tomography), muscle strength (1RM & Biodex dynamometer) and physical functioning (including 6min walk distance [6MWD]) were assessed. RESULTS: There was a sex-related dichotomy in the heat shock response to high external load training. We observed a significant decrease in eHsp70 concentration in the HIGH group for female, but not male, subjects. At baseline, men had a larger muscle volume, leg press and leg extension 1RM compared to women (all p

Introduction: Inflammation is related to muscle wasting in elderly persons. Since surgery is accompanied by an important inflammatory response, the degree of muscle wasting and related symptoms such as weakness and tiredness might exacerbate very rapidly in elderly surgery patients. Methods: PubMed and Web of Science were systematically screened for articles reporting the influence of surgery-induced inflammation on muscle performance and/or fatigue in elderly patients. Studies reporting surgery-induced inflammation and changes in muscle performance and/or fatigue, but without analyzing their association were excluded. Although 5 relevant articles were identified including older patients (highest ages reported were 71-92 years), none focused exclusively on elderly patients. Only 2 studies assessed muscle performance, and in none muscle mass was evaluated. Overall, we found evidence that in elderly patients higher surgery-induced inflammation was significantly related to worse muscle performance and fatigue in the first postoperative days as well as after more than one month (especially for fatigue) following the intervention. Pre-operative anti-inflammatory treatment using steroids or glucocorticoids can reduce the surgery-induced inflammatory response and improve the recovery of muscle performance and postoperative fatigue in elderly elective abdominal surgery or arthroplasty patients. Conclusion: We can conclude that to date, only few studies have investigated the association between surgery-induced inflammation and changes in postoperative muscle performance and fatigue in elderly patients. More research is warranted focusing on both the short -and long-term effects of surgical stress on muscle performance in elderly patients as well as the on risks and benefits of peri-operative anti-inflammatory treatment.

Objectives This study aimed to examine the effects of introducing participatory action research (PAR) within the nursing home (NH) on residents’ quality of life (QoL) and NH experience and participation, and to explore their experiences with PAR. Design A mixed methods design was chosen, including a clustered randomized controlled trial (RCT) and qualitative interviews. Setting For the RCT, 3 NHs were randomly allocated to 3 conditions: an intervention (weekly PAR activity), an active control (weekly reminiscence-activity), or passive control (care as usual). The qualitative study took place in the intervention NH. Participants Within the RCT, about 30 residents were recruited for assessments per NH, including 9 PAR participants and 10 reminiscence participants. Qualitative interviews were held with all PAR participants (residents and internal moderator). Intervention PAR is a method to structurally involve residents in the NH operation. Weekly PAR sessions were held with 9 residents and 2 moderators. Here, residents critically analyzed and discussed the NH operation, identified possible problems, suggested improvements, which were further implemented by the NH and monitored by the PAR group. Measurements Residents’ NH experience (NH Active Aging Survey), QoL (Anamnestic Comparison Self-Assessment), and experienced participation (Impact on Participation and Autonomy) were measured in the RCT at pre-test, post-test (6 months), and follow-up (12 months). The qualitative study took into account interviews with the PAR stakeholders after 6 months. Results The RCT showed residents’ QoL improving more between pre-test and follow-up in the intervention and active control NH compared with the passive control NH. No other effects were observed. The qualitative data revealed a positive PAR experience. Participants enjoyed the activity and indicated various positive influences. Still, there was room for improvement, including communication toward other residents and between staff. Conclusions Notwithstanding the modest quantitative effects, PAR led to positive experiences and can have a future in the NH when solving some limitations.

Care plans are intended to improve the independence and functioning of patients with cognitive dysfunction and support the caregivers involved. They are an integral part of the Belgian reimbursement procedure for cholinesterase inhibitors. This nationwide, multicenter, observational study examined the content and implementation of the care plan along with patient satisfaction in community-dwelling patients newly diagnosed with Alzheimer disease in Belgium. The patients' opinion of their quality of life was measured using Anamnestic Comparative Self-Assessment (ACSA) scale. A total of 720 participants (453 female) were enrolled with 86.0% (619/719) living at home alone or with their spouse/partner. Cognitive problems (627/717, 87.4%) were the main reason for initiation of the consultation. Most patients had a caregiver (646/719, 89.8%): generally the spouse/partner (351/646, 54.3%) or a child (232/646, 35.9%). A total of 511 patients (71.0%) were prescribed a cholinesterase inhibitor after the initial consultation. A total of 236 care plans were advised with 169 (71.6%) realized and 157 of these (92.9%) considered adequate. Most patients were satisfied with the help received in the care plan (service satisfaction range, 80.0% to 98.6% of patients). Quality of life as rated by the patient significantly increased between baseline (average ACSA score: 5.2 +/- 2.4) and follow-up (5.8 +/- 2.1). The use of care plans appears to improve management of care for Alzheimer disease patients.

Geriatric patients with acute infection show increased muscle weakness and fatigability but the relative contribution of central and peripheral factors is unclear. Hospitalised patients with acute infection (82±6years, N=10) and community-dwelling controls (76±6years, N=19) sustained a maximal voluntary isometric contraction of the M. Adductor Pollicis until strength dropped to 50% of its maximal value. Voluntary muscle activation (VA) was assessed before and at the end of the fatigue protocol using twitch interpolation method and muscle activity was monitored using surface electromyography. Twenty-five circulating inflammatory biomarkers were determined. At pre-fatigue, no significant difference in VA was found between groups. VA decreased to similar levels (~50%) at the end of the fatigue protocol with no association with inflammatory biomarkers. In geriatric patients, muscle activity decreased significantly (p

Nursing homes should support residents’ quality of life (QoL). It remains vague, however, how these facilities can create a QoL enhancing environment. Active ageing (AA) is a useful framework in this context, since it provides a multidimensional set of determinants that enhance QoL. This study examined the current status of AA in nursing homes in Flanders, Belgium. A sample of 383 randomly recruited residents was surveyed on the subjective importance and experienced reality of the AA determinants as well as on QoL. Based on descriptive analyses, residents appeared to have a positive QoL and a moderately positive appraisal of the extent to which nursing homes provide a multidimensional environment to enhance their QoL. Multivariate analyses showed that residents’ nursing home active ageing (NHAA) experience was positively related to their QoL and explained 20 % of its variance. Specifically, psychological factors and participation related positively to QoL. Demographic variables showed no relationships with QoL, while educational level related negatively to the NHAA experience. Currently, in Flanders, nursing homes are on their way to working according to the AA vision, but further efforts are still needed.

According to the promising results of the Phase I and Phase IIA clinical trials with the herbal medicinal product PR 259 CT1 consisting of an 80 % ethanolic extract of the stem bark of Nauclea pobeguinii containing 5.6 % strictosamide, a Phase IIB study was conducted as a single blind prospective trial in 65 patients with proven Plasmodium falciparum malaria to evaluate the effectiveness and safety of this herbal drug. The study was carried out simultaneously using an artesunate-amodiaquine combination (Coarsucam®) as a positive control. This combination is the standard first-line treatment for uncomplicated malaria recommended by the National Programme of Malaria Control in the Democratic Republic of Congo (DR Congo). With regard to PR 259 CT1, patients were treated with a drug regimen of two 500-mg capsules three times daily for three days in the inpatient clinic, followed by out-patient treatment of one 500-mg capsule three times daily during the next four days; the positive control group received two tablets containing 100 mg artesunate and 270 mg amodiaquine (fixed-dose) once daily during three consecutive days. Antimalarial responses were evaluated according to the WHO 2003 guideline for a 14-day test. The results from the physical and laboratory examinations did not show any significant changes in values of vital signs, ECG, biochemical, and haematological parameters. The study showed a significant decreased parasitaemia in patients treated with PR 29 CT1 and artesunate-amodiaquine with adequate clinical parasitological responses (APCR) at day 14 of 87.9 and 96.9 %, respectively. The former product was better tolerated than the latter since more side effects were observed for the artesunate-amodiaquine combination. These results indicated that PR 259 CT1 can be considered as a promising candidate for the development of a herbal medicine for the treatment of uncomplicated falciparum malaria.

The aim of this phase IIA clinical trial was to assess the efficacy of an 80 % ethanolic quantified extract (containing 5.6 % strictosamide as the putative active constituent) from Nauclea pobeguinii stem bark denoted as PR 259 CT1 in a small group of adult patients diagnosed with uncomplicated falciparum malaria. Results obtained from a phase I clinical trial on healthy male volunteers indicated that the oral administration during meals of two 500 mg capsules three times daily (each eight hours) during seven days was well tolerated and showed only mild and self-resolving adverse effects. This PR 259 CT1 drug regimen was obtained by mathematical conversion of animal doses obtained in several in vivo studies in mice to human equivalent doses as in falciparum malaria patients. The phase IIA study was an open cohort study in eleven appraisable adult patients suffering from proven Plasmodium falciparum malaria. The study was specifically designed to assess the efficacy of PR 259 CT1 administered with a dose regimen of two 500 mg capsules three times daily for three days, followed by outpatient treatment of one 500 mg capsule three times daily for the next four days, in order to prove that this therapeutic dose, which was calculated from animal doses, was effective to treat adult malaria patients and consequently useful for a future Phase IIB clinical trial. This study would then substitute a dose-escalating trial, which in general is used to find the appropriate dose for clinical studies. The phase IIA clinical trial was carried out according to the WHO 2003 14-day test, and the results revealed that all eleven patients were completely cleared of parasitemia and fever on days 3, 7, and 14 except for one patient, who experienced a recurrence of parasitemia at days 7 until 14. Besides this adequate clinical and parasitological response (ACPR), this trial also demonstrated that PR 259 CT1 was well tolerated with only mild and self-resolving adverse effects including fatigue and headache, which were in accordance with those found in the phase I clinical trial. Moreover, all symptoms progressively disappeared, and no symptoms were observed on day 14. Although the number of patients included in this study was rather limited, the statistical analysis nevertheless suggested the efficacy and tolerability of PR 259 CT1, which indicated that this herbal medicinal product might be considered as a putative candidate for a large scale clinical trial.

Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection. Patients were randomized to receive either 10 mg piroxicam or placebo. Patients >/= 70 years with CRP levels >10 mg/L of acute infectious origin were eligible. Twenty-five cyto-/chemokines as well as heat shock proteins Hsp27 (HSPB1) and Hsp70 (HSPA1A) were measured the first 4 days and then weekly until discharge, with a maximum of 3 weeks. Thirty Caucasian patients were included (median age 84.5 years, 67% female, median CRP 87.5 mg/L). In the piroxicam group, IL-6 and IP-10/CXCL10 decreased significantly during the study period. Relationships between cytokines were disrupted in the piroxicam group: for 12 out of 20 cytokines the number of correlations between changes in serum levels was significantly lower compared to placebo. Serum Hsp70 levels decreased significantly in the piroxicam group, but not in the placebo group. Without heat challenge, intracellular levels of Hsp70 in monocytes decreased in both groups, whereas HsP27 in monocytes increased with piroxicam with a significant difference compared to placebo at 3 weeks. Piroxicam in this setting cannot be considered merely as an anti-inflammatory drug, but rather as an immunomodulator. Further studies are needed to establish whether these effects can change functional outcomes in geriatric patients.

Background: In older patients, evaluation of the cognitive status is crucial. The Mini-Mental State Examination (MMSE) is widely used for screening of cognition, providing fairly high sensitivity, specificity and reproducibility. Recently, a consensus emerged on the necessity of an international and transparent language, as provided by the WHO’s International Classification of Functioning, Disability and Health (ICF). Most assessment tools however are not in accordance with the ICF. Objective: To reformulate the MMSE according to the ICF, both for the individual items and for the scoring system. Method: MMSE data (scores varying from 3 to 30/30) of (1) 217 cognitively healthy elderly, (2) 60 persons with mild cognitive impairment, (3) 60 patients with mild Alzheimer’s disease (AD), and (4) 60 patients with moderate/severe AD were obtained from studies at a university hospital setting. Subjects were aged 65 years or more and recruited either through advertisement (group 1), from the geriatric day hospital (groups 2 and 3), or the geriatric ward (group 4). The allocation to the groups was done after multidisciplinary evaluation. The conversion of the MMSE to ICF-MMSE was done by content comparison and by subsequent translation of the scoring system using automatic algorithms. Results: All MMSE items were converted to the corresponding ICF categories. Three ICF domains were addressed: global and specific mental functions, general tasks and demands, divided over 6 ICF categories (orientation time/place, sustaining attention, memory functions, mental functions of language, undertaking a simple task). Scores on individual items were transformed according to their relative weight on the original MMSE scale, and a total ICF-MMSE score from 0 (no problem) to 100 (complete problem) was generated. Translation was satisfying, as illustrated by a good correlation between MMSE and ICF-MMSE. The diagnostic groups were distributed over the ICF-MMSE scores as expected. For each ICF domain, ICF-MMSE subscores were higher with increasing severity in cognitive decline. There was a higher dispersion, in accordance with the more detailed scoring possibilities of the ICF-MMSE. Conclusions: It is possible to adapt the MMSE to the ICF concept. This adaptation enhances interdisciplinary communication since it provides more clarity in assessment, with better visibility of the areas covered by the instrument.

Aim: To record in real life the appreciation of elderly patients, their caregivers and physicians of a once daily formulation of prolonged release of galantamine in the treatment of mild to moderate Alzheimer's disease. Methods: A prospective, multicenter, observational study was conducted in 128 elderly patients, treated for 6 months with galantamine, donepezil or rivastigmine. Results: Of the patients treated with galantamine, 82 of the 97 (84.5%) were continuing their treatment after 6 months. These patients reported their condition as improved in 49%, unchanged in 47% and worsened in 4%. Caregivers rated global evaluation as 37% better, 41% unchanged and 22% worse. Physicians rated global clinical impression of change as 46% better, 34% unchanged and 20% worse. Measurements of cognition and behavior remained stable. The appreciation of physicians and caregivers corresponded well (P

Background: Accurate medication histories at hospital admission are an important element of medication safety. Discrepancies may have clinically significant consequences, especially in the elderly population. Objective: To assess the clinical pharmacist's performance in obtaining patients' medication histories and in reconciling these data with the medical records and medication orders and whether the patients' residential situation prior to hospitalization influences the number of drug discrepancies. Methods: A prospective observational study was conducted at a 29-bed acute geriatric ward of a Belgian university hospital. Medication histories acquired by clinical pharmacists were compared with those documented in the medical records by the attending physicians. All discrepancies were identified and categorized by an independent pharmacist and were scored for their clinical relevance in consensus by a senior internist and a senior geriatrician. Results: Of the 215 screened geriatric (aged ≥66 years) patients admitted between October 27, 2007, and September 23, 2008, 197 were enrolled in the study. For patients living in the community, as well as those residing in a nursing home prior to hospitalization, clinical pharmacists identified significantly more preadmission drugs compared with physicians, with a median number of 8 correctly identified medications versus 6, respectively (p < 0.001). Extra identified drugs consisted of over-the-counter as well as prescription medications. Furthermore, 117 other medication discrepancies were noted, mainly related to erroneous drug identification and incorrect drug dose. In all, the clinical pharmacists identified 379 (24.2%) medication discrepancies, of which 188 (49.6%) were judged clinically relevant. Conclusions: Pharmacist-acquired medication histories enhance the medication reconciliation process, both in patients residing at home and in a nursing home prior to hospitalization. A focus should be placed on seamless care procedures that facilitate the transfer of medication histories between primary and secondary care in both of these populations.

Objective To explore the feasibility and effects of rehabilitation using manual mobilization of the thoracic spine in elderly female patients with osteoporosis. Methods Forty-eight postmenopausal patients with osteoporosis (age 76 -/+ 7 years) were randomly assigned to 3 months rehabilitation (18 sessions including manual mobilization, taping and exercises, n = 29) or control (wait-list, n = 19). The primary outcome was thoracic kyphosis degree (Spinal-Mouse). Secondary outcomes were back pain (visual analogue scale) and quality of life (Qualeffo-41). Explanatory outcomes were compliance with rehabilitation, complications, and patients' and therapists' perceptions regarding the rehabilitation programme. Results Thoracic kyphosis improved significantly following rehabilitation compared with controls (intention-to-treat analysis, p = 0.017); and in patients who were compliant with rehabilitation (n = 15) compared with those who were non-compliant (p = 0.002) and controls (p = 0.001). Mental health worsened slightly in the rehabilitation group (p = 0.029), but not significantly compared with controls. Neither patients nor physical therapists reported serious adverse effects. Conclusion Three months of rehabilitation with manual mobilization can attenuate thoracic kyphosis in elderly patients with osteoporosis. Its impact on back pain and quality of life remains unclear and needs further investigation.

Objective: Since the number of older people is rising worldwide, there is an increasing need for a structured and integrated approach for the participation of the older person in clinical research. The introduction of a 'Geriatric Minimum Data Set' (GMDS) will allow a standardized description of the older person participating in clinical research. ICF, a universal tool for the comprehensive description of human functioning, developed by the World Health Organisation, can make a substantial contribution to the development of a GMDS. It can serve as a 'framework', including all the functional characteristics needed in research in Gerontology and Geriatrics. The objective was to integrate ICF terminology in a recently proposed GMDS-25. Design: ICF is explored to determine the most relevant ICF-categories for GMDS-25. Results and conclusion: Several items of the GMDS-25 can be described in terms of ICF. This description contributes to the optimal standardization of the GMDS-25.

OBJECTIVES: To explore the relationships between muscle endurance and circulating interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and heat shock protein (Hsp)70 in nursing home residents and to assess how muscle endurance relates to self-perceived fatigue and mobility. DESIGN: Exploratory study. SETTING: Three nursing homes of the Foundation for Psychogeriatrics (Brussels, Belgium). PARTICIPANTS: Seventy-seven residents (53 female and 24 male, mean age 81 ± 8). MEASUREMENTS: Participants were assessed for muscle endurance (fatigue resistance and grip work); perceived fatigue (visual analogue scale for fatigue); fatigue during daily activities (Mobility-Tiredness Scale); effect of fatigue on quality of life (World Health Organization Quality Of Life questionnaire); mobility (Tinetti Test & Elderly Mobility Scale (EMS)); and circulating IL-6, TNF-α, and Hsp70. RESULTS: Residents with better fatigue resistance reported less self-perceived tiredness (P

To examine the effect of galantamine in elderly patients with mild to moderate Alzheimer disease (AD) on reaction time (RT), selective (SA) and alternating attention (AA), errors, and on interindividual and intraindividual variability.Forty-one outpatients with AD were included in an open-label prospective trial and evaluated at baseline and after 8 and 22 weeks of treatment using a RT test that allows differentiation between the decision and movement time components of the total RT. The various tasks of the RT test allowed calculation of SA and AA. Standard AD evaluation tests were performed at baseline and after 22 weeks.After 8 and 22 weeks of treatment, an improvement of decision time and RT at all complexity levels was noted. For movement time, improvements were less pronounced and not present at both follow-up moments or at all complexity levels. Selective attention, but not AA, improved significantly after 22 weeks. A decrease in the number of errors was noted. At several complexity levels, both at 8 and 22 weeks, the interindividual and intraindividual variability decreased. Changes in Mini Mental State Evaluation score were correlated with those in SA.Our study provides arguments that galantamine treatment improves various parameters of the RT, attention, and interindividual and intraindividual variability in elderly AD patients. Because the study is not a controlled trial, further investigation is needed.

Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly inducible by a variety of stressful stimuli. As organisms age, various denatured proteins such as proteins modified by oxidation have been detected. Such abnormal proteins might serve as stress signals for the induction of Hsp, which plays indispensable roles in protecting proteins from denaturation. Although it is well known that the heat shock induced expression of Hsp decreases with age, little attention has been given to the unstimulated, basal levels of Hsp. Therefore, a study was performed to examine the expression pattern of various Hsp with aging, under normal physiological conditions in human peripheral blood cells. The basal levels of Hsp32, Hsp70 and Hsp90 increased significantly with age in controls but not patients. Moreover, the levels of Hsp32, Hsp70, Hsp90, but not Hsp27 correlated positively among each other, indicating both common and different regulatory mechanisms. Higher levels of Hsp32, Hsp70 and Hsp90 were noticed in patients with inflammation, a commonly occurring natural stimulant of Hsp production, compared to control subjects. The production of Hsp appeared to be related to the circulating levels of C-reactive protein and cytokines.

Background & aims No generalizable formulas exist that are derived from bioelectrical impedance analysis (BIA) for predicting appendicular lean mass (ALM) and fat mass (AFM) in sarcopenic older adults. Since precision of regional body composition (BC) data in multicentre trials is essential, this study aimed to: 1) develop and cross-validate soft tissue BIA equations with GE Lunar and Hologic DXA systems as their reference 2) to compare our new ALM equation to two previously published models and 3) to assess the agreement between BIA- and DXA-derived soft tissue ratios as indicators of limb tissue quality. Methods Two-hundred and ninety-one participants with functional limitations (SPPB-score 4–9; sarcopenia class I or II, measured by BIA) were recruited from 18 study centres in six European countries. BIA equations, using DXA-derived ALM and AFM as the dependent variable, and age, gender, weight, impedance index and reactance as independent variables, were developed using a stepwise multiple linear regression approach. Results Cross-validation gave rise to 4 equations using the whole sample: ALMLUNAR (kg) = 1.821 + (0.168*height2/resistance) + (0.132*weight) + (0.017*reactance) − (1.931*sex) [R2 = 0.86 and SEE = 1.37 kg] AFMLUNAR (kg) = −6.553 − (0.093* height2/resistance) + (0.272*weight) + (4.295*sex) [R2 = 0.70 and SEE = 1.53 kg] ALMHOLOGIC (kg) = 4.957 + (0.196* height2/resistance) + (0.060*weight) − (2.554*sex) [R2 = 0.90 and SEE = 1.28 kg] AFMHOLOGIC (kg) = −4.716 − (0.142* height2/resistance) + (0.316*weight) + (4.453*sex) − (0.040*reactance) [R2 = 0.73 and SEE = 1.54 kg] Both previously published models significantly overestimated ALM in our sample with biases of −0.36 kg to −1.05 kg. For the ratio of ALM to AFM, a strong correlation (r = 0.82, P

BACKGROUND: Changes in sub-populations of cytotoxic (CD8(+)) T-cells, which are observed in aging and in conditions of chronic immune stimulation, are not well-documented in cancer. MATERIALS AND METHODS: Using flow cytometry, CD8(+) T-cell subsets were analyzed in patients with breast cancer undergoing DNA-damaging chemotherapy and in an older female control group during a six-month longitudinal study, to explore shifts in CD8(+) T-cells and the effect of DNA-damaging chemotherapy on different T-cell sub-populations. RESULTS: As expected, there was a consistent decrease in absolute numbers of leukocytes, lymphocytes, T-cells and CD8(+) T-cells during chemotherapy in patients with cancer. Among the T-cells, there was a lower CD8(-)/CD8(+) ratio, persisting over the six months, in patients with cancer compared to controls. The proportion of CD28(-)CD57(+) cells also remained higher among patients with cancer throughout the sampling duration. The number of CD28(+)CD57(-) and CD28(-)CD5(-) cells decreased faster during DNA-damaging chemotherapy than CD28(+)CD57(+) and CD28(-)CD57(+) cells, while only CD28(-)CD57(-) cells showed a significant reconstitutive capacity after six months. CONCLUSION: Immunosenescence appeared to be pronounced in patients with breast cancer, with senescent CD8(+) T-cells playing a role. The normal condition was not restored after six months of chemotherapy.

Background and aims: Although a wide variety of protocols are available for evaluating skeletal muscle fatigue resistance, they often necessitate important technological resources or are too complicated for elderly subjects. We present here a new test, designed for elderly persons, based on maintaining maximal voluntary grip strength as long as possible. The aim of the study was to determine the reliability of this test procedure in hospitalized geriatric patients and in young healthy persons. Methods: Fatigue resistance was considered as the time in which grip strength decreases to 50% of its maximum value. Twenty geriatric, hospitalized patients (age 83±6 yrs) and thirty-nine young, healthy persons (age 23±4 yrs) were evaluated for fatigue resistance by two different observers. Height, weight and body mass index were determined for each participant and the current amount of sports activity was recorded in the young subjects. Results: All participants were able to perform the test. Inter- and intra-rater reliability in both subgroups was good to excellent, with ICC(3,1) values ranging from 0.77 to 0.94. No significant differences in inter- and intra-rater measurements were found, except for inter-observer evaluations of the dominant hand in hospitalized geriatric patients. No significant relationships were found between fatigue resistance and maximal grip strength, anthropometrics or gender. Conclusions: The proposed fatigue resistance test is a reliable tool to evaluate geriatric hospitalized patients as well as young, active and healthy persons. Fatigue resistance scores are not related to gender, maximal strength or anthropometrics within the observed subgroups.

BACKGROUND: Acute inflammation has a negative effect on the muscular system in elderly patients, compromising the outcome of the underlying disease. OBJECTIVE: The aim of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibition on muscle performance and mobility in hospitalized elderly patients with acute inflammation of infectious origin. METHODS: In this single-blind, controlled trial, consecutively hospitalized elderly patients (age > or = 70 years) with inflammation (C-reactive protein [CRP] levels > or =10 mg/L) due to acute infection were randomly assigned to receive 2 weeks of treatment with the COX-2-selective inhibitor celecoxib, acetaminophen, or no supplementary medication (control). The following variables were assessed at baseline and at 1 and 2 weeks' follow-up: muscle fatigue resistance (primary outcome measure); grip strength and mobility (secondary outcome measures); and levels of the acute-phase markers CRP, interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha(TNF-alpha), and transforming growth factor-beta (TGF-beta) as explanatory variables. RESULTS: Forty-three consecutively hospitalized elderly patients (31 women, 12 men; mean [SD] age, 84 [6] years) were enrolled. Fourteen patients received celecoxib, 14 received acetaminophen, and 15 received no supplementary medication. The change in fatigue resistance was significantly different between groups (P = 0.021, Kruskal-Wallis chi-square test), with significantly greater improvement in patients receiving celecoxib compared with the acetaminophen and control groups (63% increase from baseline; P

Heat shock proteins (Hsp) form a large family of proteins that are ubiquitously present in all organisms. In the absence of destabilising stimuli, Hsp are expressed at low levels, but their expression can be highly induced by various noxious conditions such as heat, oxygen stress and infection. Hsp have been reported to interfere with inflammatory processes and their induction is well known to decrease with aging. In the present study we have investigated Hsp 70 serum concentrations using an optimised ELISA in elderly patients, recruited from a geriatric University Hospital ward. Our results portray positive correlations between the serum levels of Hsp 70 and various markers of inflammation (monocyte count, serum concentration of TNF-alpha, plasma concentrations of C-reactive protein, and fibrinogen), explaining the difference in Hsp 70 serum concentrations in these subjects with various degrees of inflammation. We conclude that Hsp 70 is involved in inflammatory diseases and that the serum level of Hsp 70 is directly linked to the inflammatory status of the subject. However, the nature of this relationship remains to be elucidated.

Digoxin intoxication is a very common finding in elderly patients (1-3). The narrow toxic-therapeutic margin is more difficult to estimate in the elderly, due to their physiologically impaired renal function, the decreased lean body mass and the smaller volume of distribution (Vd) at older age. Electrolyte imbalance and associated drug interactions can increase the sensitivity for digoxin. When intoxication occurs, the first action taken is to stop digoxin, so that serum levels drop and toxicity dissipates. However, in a few occasions serum levels can further increase despite withdrawal. We present a case in which digoxin serum levels continued to rise for several days after digoxin discontinuation. This unusual mechanism for toxicity is further explained. To our knowledge, six cases of rising digoxin levels without further administration have been reported in the literature (4-8). CASE REPORT

We have investigated the effect of age and of the presence of proinflammatory cytokines on Hsp 70 production in human peripheral blood mononuclear cells, using flow cytometry. Twenty-seven women and 23 men, all apparently healthy, participated in the study. At 37°C, the percentage of Hsp 70-producing monocytes and lymphocytes, as well as the level of Hsp 70 in monocytes, were negatively influenced by age. After exposure of the cells to 42°C, the increase of Hsp 70 production was more pronounced in monocytes than in lymphocytes; both the intensity of Hsp 70 production and the percentage of Hsp 70-producing cells were negatively influenced by the age of the subjects, as well for monocytes as for lymphocytes. There was a negative correlation between the intensity of Hsp 70 production by monocytes exposed to 42°C and the serum levels of tumor necrosis factor-α and interleukin-6. In conclusion, in human monocytes and lymphocytes, heat-induced Hsp 70 production is reduced with increasing age and is negatively influenced in monocytes by proinflammatory cytokines.

BACKGROUND: Shifts in CD8+ T-cell subsets that are hallmarks of immunosenescence are observed in ageing and in conditions of chronic immune stimulation. Presently, there is limited documentation of such changes in lung cancer and other malignancies affecting the lungs. METHODS: Changes in CD8+ T-cell subsets, based on the expression of CD28 and CD57, were analysed in patients with various forms of cancer affecting the lungs, undergoing chemotherapy and in a control group over six months, using multi-colour flow cytometry. RESULTS: The differences between patients and controls, and the changes in the frequency of CD8+ T-cell subpopulations among lung cancer patients corresponded to those seen in immunosenescence: lower CD8-/CD8+ ratio, lower proportions of CD28+CD57- cells consisting of naïve and central memory cells, and higher proportions of senescent-enriched CD28-CD57+ cells among the lung cancer patients, with the stage IV lung cancer patients showing the most pronounced changes. Also observed was a tendency of chemotherapy to induce the formation of CD28+CD57+ cells, which, in line with the capacity of chemotherapy to induce the formation of senescent cells, might provide more evidence supporting CD28+CD57+ cells as senescent cells. CONCLUSION: Immunosenescence was present before the start of the treatment; it appeared to be pronounced in patients with advanced cases of malignancies affecting the lungs, and might not be averted by chemotherapy.