Introducing a pharmacist-led transmural care program to reduce drug-related problems in orthogeriatric patients: a prospective interventional study.

BACKGROUND: Orthogeriatric patients have an increased risk for complications due to underlying comorbidities, chronic drug therapy and frequent treatment changes during hospitalization. The clinical pharmacist (CP) plays a key role in transmural communication concerning polypharmacy to improve continuity of care by the general practitioner (GP) after discharge. In this study, a pharmacist-led transmural care program, tailored to orthogeriatric patients, was evaluated to reduce drug related problems (DRPs) after discharge. METHODS: An interventional study was performed (pre-period: 1/10/2021-31/12/2021; post-period: 1/01/2022-31/03/2022). Patients (≥ 65 years) from the orthopedic department were included. The pre-group received usual care, the post-group received the pharmacist-led transmural care program. The DRP reduction rate one month after discharge was calculated. Associated factors for the DRP reduction rate were determined in a multiple linear regression analysis. The GP acceptance rate was determined for the proposed interventions, as well as their clinical impact using the Clinical, Economic and Organizational (CLEO) tool. Readmissions one month after discharge were evaluated. RESULTS: Overall, 127 patients were included (control n = 61, intervention n = 66). The DRP reduction rate was statistically significantly higher in the intervention group compared to the control group (p < 0.001). The pharmacist's intervention was associated with an increased DRP reduction rate (+ 1.750, 95% confidence interval 1.222-2.278). In total, 141 interventions were suggested by the CP, of which 71% were accepted one month after discharge. In both periods, four patients were readmitted one month after discharge. 58% of the interventions had a clinical impact (≥ 2 C level using the CLEO-tool) according to the geriatrician and for the CP it was 45%, indicating that they had the potential to avoid patient harm. CONCLUSIONS: The pharmacist-led transmural care program significantly reduced DRPs in geriatric patients from the orthopedic department one month after discharge. The transmural communication with GPs resulted in a high acceptance rate of the proposed interventions.

Tandem Use of OvMANE1 and Ov-16 ELISA Tests Increases the Sensitivity for the Diagnosis of Human Onchocerciasis.

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.

Onchocerciasis Fingerprints in the Geriatric Population: Does Host Immunity Play a Role?

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 phenotypes, 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.

Inverted circadian variation of arterial pressure in a geriatric patient: an indicator of autonomic dysfunction.

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.

Effect of Antihypertensive and Statin Medication Use on Muscle Performance in Community-Dwelling Older Adults Performing Strength Training.

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], ß-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.

Pharmacologic Treatment for Hypoactive Delirium in Adult Patients: A Brief Report of the Literature.

OBJECTIVES: The purpose of this report was to identify medications that can be used to treat hypoactive delirium. DESIGN: A systematic search of PubMed and Web of Science from inception through September 20, 2020. SETTING AND PARTICIPANTS: Reports evaluating different pharmacologic treatments for hypoactive delirium in adults (age 18 years and older) and geriatric patients were included. METHODS: Three independent investigators reviewed the abstracts, using the Rayyan QCRI review tool to decide which articles were eligible for inclusion. Hereafter, articles were read completely for final inclusion. Study quality was assessed using the guidelines from the National Institute for Health and Care Excellence for cohort studies and randomized control trials. RESULTS: Of the 52 relevant articles, only 4 (8%) met the selection criteria. Two were cohort studies whereas the other 2 were randomized control trials. After further review, one of the reports was excluded because the same data were used as in one of the randomized control trials. In total, 4 different pharmacologic therapies were used in the selected studies: haloperidol, ziprasidone, aripiprazole, and methylphenidate. Aripiprazole showed a complete resolution of hypoactive delirium (P < .001), and methylphenidate showed a significant amelioration in cognitive function (P < .001). Ziprasidone and haloperidol did not show significant differences compared with placebo. CONCLUSIONS AND IMPLICATIONS: A limited number of clinical studies on the treatment of hypoactive delirium are available. Aripiprazole and methylphenidate showed promising results in the treatment of hypoactive delirium.

A Novel Bead-Based Immunoassay for the Measurement of Heat Shock Proteins 27 and 70.

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.

Is inflammageing influenced by the microbiota in the aged gut? A systematic review.

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-ß, 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.

Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.

AIMS: Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. METHODS: A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. RESULTS AND DISCUSSION: In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. CONCLUSION: A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.

Analysis of inflammatory markers and hormones in old cancer patients: A descriptive study.

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.

A Vitamin D, Calcium and Leucine-Enriched Whey Protein Nutritional Supplement Improves Measures of Bone Health in Sarcopenic Non-Malnourished Older Adults: The PROVIDE Study.

Alterations in musculoskeletal health with advanced age contribute to sarcopenia and decline in bone mineral density (BMD) and bone strength. This decline may be modifiable via dietary supplementation. To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of bone health. Participants (n 380) were participants of the PROVIDE study, a 13-week, multicenter, randomized, controlled, double-blind, 2 parallel-group study among non-malnourished older participants (≥ 65 years) with sarcopenia [determined by Short Physical Performance Battery (SPPB; 0-12) scores between 4 and 9, and a low skeletal muscle mass index (SMI; skeletal muscle mass/BW × 100) ≤ 37% in men and ≤ 28% in women using bioelectric impedance analysis] Supplementation of a vitamin D, calcium and leucine-enriched whey protein drink that comprises a full range of micronutrients (active; 2/day) was compared with an iso-caloric control. Serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), biochemical markers of bone formation (osteocalcin; OC, procollagen type 1 amino-terminal propeptide; P1NP) and resorption (carboxy-terminal collagen crosslinks; CTX), insulin like growth factor 1 (IGF-1) and total-body BMD were analysed pre- and post-intervention. Serum 25(OH)D concentrations increased from 51.1 ± 22.9 nmol/L (mean ± SD) to 78.9 ± 21.1 nmol/L in the active group (p < 0.001 vs. control). Serum PTH showed a significant treatment difference (p < 0.001) with a decline in the active group, and increase in the control group. Serum IGF-1 increased in the active group (p < 0.001 vs. control). Serum CTX showed a greater decline in the active group (p = 0.001 vs. control). There were no significant differences in serum OC or P1NP between groups during the intervention. Total body BMD showed a small (0.02 g/cm2; ~ 2%) but significant increase in the active group after supplementation (p = 0.033 vs. control). Consuming a vitamin D, calcium and leucine-enriched whey protein supplement for 13 weeks improved 25(OH)D, suppressed PTH and had small but positive effects on BMD, indicative of improved bone health, in sarcopenic non-malnourished older adults.

Trunk inclination and hip extension mobility, but not thoracic kyphosis angle, are related to 3D-accelerometry based gait alterations and increased fall-risk in older persons.

BACKGROUND: Only a portion of the increased variability in gait parameters observed in ageing can be explained by age and gait speed alone. Other factors, like musculoskeletal changes of the spine, might contribute to higher variability of gait parameters, slower walking speed and subsequently increased fall-risk in ageing. RESEARCH QUESTION: Are spinal posture and mobility related to 3D-accelerometry based gait analysis, functional performance and fall-risk in ageing? METHODS: Forty elderly presenting increased fall-risk (OFR, 80.6 ±â€¯5.4yrs), 41 old controls (OC, 79.1 ±â€¯4.9yrs), and 40 young controls (YC, 21.6 ±â€¯1.4yrs) were assessed for spinal posture and mobility (SpinalMouse®), gait analysis (DynaPort MiniMod), and functional performance (grip strength, grip work, timed-get-up-and-go-test, performance-oriented mobility assessment). RESULTS: Compared to OC, OFR showed significantly (p < .05) larger trunk inclination angle (INC), smaller sacral extension mobility, slower walking speed, and lower medio-lateral step and stride regularity. Thoracic kyphosis angle (TKA) was similar in all groups. INC and sacral extension mobility showed the highest correlation with walking speed, gait parameters, functional performance and fall-risk. INC (OR = 1.14) and sacral extension mobility (OR = 1.12) can moderately explain fall-risk in elderly participants and showed fair capacity to discriminate OFR from OC, the diagnostic value on fall-risk is however low (best probabilistic cut-off value, INC: -0.83° [sensitivity = 70%, specificity = 61%, PPV = 64%, NPV = 68%, LR+ = 1.79, LR- = 0.49, AUC = 0.71]; sacral extension mobility: 8.5° [sensitivity = 70%, specificity = 73%, PPV = 72%, NPV = 71%, LR+ = 2.61, LR -= 0.41, AUC = 0.71]). SIGNIFICANCE: Larger trunk inclination and smaller sacral extension mobility (i.e. hip extension mobility) are moderately related to increased fall-risk, gait alterations, lower muscle performance and worse functional mobility in ageing. Contrary to our hypothesis, TKA showed no relation with parameters of gait and/or fall-risk. INC and sacral extension mobility have fair discriminative power to distinguish older persons with increased fall-risk from those without and might be considered as therapeutic targets.

Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study.

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 < 0.001, respectively). For IL-6 a significant time × treatment interaction (p = 0.046) was observed, with no significant change over time in the active group (p = 0.155) compared to control (significant increase p = 0.012). IL-8 showed an overall significant decrease (p = 0.03). The change in pre-albumin was a significant predictor for changes in IL-6 after 13 weeks. CONCLUSIONS: We conclude that 13 weeks of nutritional supplementation with VitD and leucine-enriched whey protein may attenuate the progression of CLIP in older sarcopenic persons with mobility limitations.

Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role?

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty. One hundred seventy-three persons aged 80 to 99 years were enrolled. Pre-frailty was defined according to Fried's criteria. Anti-CMV IgG and serum IL-6 were measured using Architect iSystem and Luminex, respectively. T-cell phenotypes were determined using flow cytometry. The prevalence of pre-frailty was 52.6%, increased with age (p = .001), and was greater in men than women (p = .044). No relationship was found between pre-frailty and positive CMV serology. Further, CMV-seropositivity was significantly associated with less naïve cells, more memory and senescence-prone phenotypes (all p < .001). After adjusting for potential confounders, only IL-6, age and sex were predictive of pre-frailty. We conclude that the presence of pre-frailty is independent from CMV infection in very old subjects.

Impact of drugs with anti-inflammatory effects on skeletal muscle and inflammation: A systematic literature review.

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.

Sufficient levels of 25-hydroxyvitamin D and protein intake required to increase muscle mass in sarcopenic older adults - The PROVIDE study.

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/h2), and relative appendicular muscle mass (aMM/body weight × 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.

Peripheral muscle fatigue in hospitalised geriatric patients is associated with circulating markers of inflammation.

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<0.05) during the fatigue protocol, whereas it increased in the controls (time∗group interaction p<0.05). The decrease in muscle activity was significantly related to higher levels of inflammation. Although slower muscle contraction and relaxation were significantly related to higher levels of inflammation, no statistical differences were found between groups. Our results confirm that muscle activity is significantly altered in older patients with acute infection and that local processes are involved.

Sex difference in the heat shock response to high external load resistance training in older humans.

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<0.001). Also, the 6MWD was significantly higher in men compared to women at baseline. However, this difference disappeared when correcting for height. Moreover, the overall functional performance and physical activity scores were similar in men and women. None of the participants' characteristics nor any of the outcome variables differed between groups at baseline. There was a significant increase in the strength and physical performance parameters in both men and women post-exercise (all p<0.05). Females in the HIGH group clearly demonstrated a larger gain in leg press 1RM and the isometric knee extensor strength compared to females in the LOW group (p=0.036 and p=0.044, respectively). More so, we found an inverse association between the change in eHsp70 levels and improvement in isometric knee extensor strength and 6MWD (r=-0.443, p=0.002 and r=-0.428, p=0.002; respectively) post exercise. CONCLUSIONS: Our results show that resistance training at high external load decreases the resting levels of eHsp70 in older females. Whether this reflects a better health status requires further investigation.

Experiences and Effects of Structurally Involving Residents in the Nursing Home by Means of Participatory Action Research: A Mixed Method Study.

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.

Predicting appendicular lean and fat mass with bioelectrical impedance analysis in older adults with physical function decline - The PROVIDE study.

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 < 0.0001) was found between the mean estimate from BIA and the DXA models without significant difference (estimated bias of 0.02 and 95% LOA -0.62, 0.65). CONCLUSION: We propose new BIA equations allowing the estimation of appendicular lean and fat mass. Our equations allow to accurately estimate the appendicular lean/fat ratio which might provide information regarding limb tissue quality, in clinical settings. Furthermore, these BIA equations can be applied to characterize sarcopenia with Hologic and Lunar reference values for BC. Previously published BIA-based models tend to overestimate ALM in sarcopenic older adults. Users of both GE Lunar and Hologic may now benefit from these equations in field research.