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.

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.

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.

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.

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.

Shifts in subsets of CD8+ T-cells as evidence of immunosenescence in patients with cancers affecting the lungs: an observational case-control study.

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.

COGNOS: care for people with cognitive dysfunction: a national observational study.

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.

The Active Ageing-concept translated to the residential long-term care.

PURPOSE: Active Ageing (AA), as described by the WHO (Active Ageing: a policy framework. World Health Organisation, Geneva 5), is an important concept in gerontology. Since the AA-concept has not been examined in the context of residential long-term care facilities, our study addresses this gap by describing the determinants of AA within this setting. METHODS: A qualitative study with semi-structured focus groups, followed by a thematic analysis, was conducted. Through purposive sampling, four focus groups of either residents of long-term care facilities (n = 8), children of residents (n = 8), community-dwelling older people (n = 8) and gerontologists (n = 6) were formed. RESULTS: The thematic analysis yielded nine determinants of AA. Seven correspond to those identified by the WHO: Culture, Behaviour, Psychological Factors, Physical Environment, Social Environment, Economic Characteristics and Health and Social Care. Two new determinants were identified: Meaningful Leisure and Participation. The determinant Participation is seen as crucial to AA in residential care. CONCLUSION: This study points to a more extensive set of determinants of AA than those identified by the WHO (Active Ageing: a policy framework. World Health Organisation, Geneva 5). Staff of long-term care facilities can make use of these determinants to promote AA in their residents.

Chronic low-grade inflammation and age-related sarcopenia.

PURPOSE OF REVIEW: Age-related chronic low-grade inflammatory profile (CLIP) has been recognized as an important causative factor for sarcopenia. Here, we report the recent evidence concerning CLIP and sarcopenia. RECENT FINDINGS: Twenty-one studies were included (12 observational, five interventional studies and four randomized controlled trials). Observational studies strengthen the association between CLIP and sarcopenia in cross-sectional and longitudinal designs. Interleukin (IL)-6 and tumour necrosis factor-α are the most reported inflammatory parameters. Biopsy studies confirm the role of oxidative mechanisms, protein kinase B and nuclear factor kappa-light-chain-enhancer of activated B cells pathways and implicate stress response mechanisms and heat shock protein. Adipose tissue as source of inflammatory cytokines remains unclear and correction for fat mass is advisable in new research. Exercise interventions (both aerobic and resistance training) demonstrate beneficial effects on CLIP even in the absence of decreases in weight, BMI or fat mass. IL-6 is also released during exercise, in hormone-like fashion unrelated to inflammation, and exercise-induced IL-6 changes require careful interpretation. Soy supplementation in one study showed no influence on CLIP and no recent pharmacological trials were retrieved. SUMMARY: Associations between CLIP and sarcopenia are observed quite consistently and underlying mechanisms become apparent. Exercise remains the mainstay intervention to lower CLIP and counter sarcopenia. More research is warranted to unravel the exact dose-response relationship.

Cellular aging and senescence characteristics of human T-lymphocytes.

CD28-, CD57+ and KLRG1+ are cell surface markers that have been used to describe senescent T-lymphocytes in humans. However, the relationship among these phenotypes during aging, and their relationship with the concept of in vitro cellular aging have not been well established. Using five-colour flow cytometry, we analyzed peripheral blood T-lymphocytes for their expression of CD28, CD57 and KLRG1 in 11 young (Y) and 11 old (O) apparently healthy human subjects. The proportions of CD28- and CD57+ cells were significantly higher among the T-cell populations of O compared to Y subjects; the proportion of KLRG1+ cells was significantly higher only among CD8+ cells. Populations that were more frequent in the elderly participants were characterised as CD28+ CD57+, CD28- CD57+ or CD28- CD57-. The expression of p16 and p21, considered as markers for in vitro senescence, was higher in CD28+ CD57+ cells than in other subpopulations in both age groups. The expression of p21 was age-related, which was not the case for p16. Thus, although both p16 and p21 are involved in T-cell senescence, they appear to behave differently. CMV infection and shifts in subpopulations are unlikely as explanations of the observed differences. Their higher levels of p16 and p21 expression, coupled with their higher prevalence in the elderly participants make CD28+ CD57+ cells the subpopulation of T-cells most closely corresponding to the concept of senescent cells.

Discrepancies in medication information for the primary care physician and the geriatric patient at discharge.

BACKGROUND: Medication discrepancies in discharge medication lists can lead to medication errors and adverse drug events following discharge. OBJECTIVE: To determine the incidence and type of discrepancies between the discharge letter for the primary care physician and the patient discharge medication list as well as identify possible patient-related determinants for experiencing discrepancies. METHODS: A retrospective, single-center, cohort study of patients discharged from the acute geriatric department of a Belgian university hospital between September 2009 and April 2010 was performed. Medications listed in the discharge letter for the primary care physician were compared with those in the patient discharge medication list. Based on the clinical pharmacist-acquired medication list at hospital admission and the medications administered during hospitalization, we determined for every discrepancy whether the medication listed in the discharge letter or the patient discharge medication list was correct. RESULTS: One hundred eighty-nine discharged patients (mean [SD] age 83.9 [5.7] years, 64.0% female) were included in the study. Almost half of these patients (90; 47.6%) had 1 or more discrepancies in medication information at discharge. The discharge letters were often more complete and accurate than the patient discharge medication lists. The most common discrepancies were omission of a brand name in the patient discharge medication list and omission of a drug in the discharge letter. Increasing numbers of drugs in the discharge medication list (OR 1.19; 95% CI 1.07 to 1.32; p = 0.001) and discharge letter (OR 1.18; 95% CI 1.07 to 1.32; p = 0.001) were associated with a higher risk for discrepancies. CONCLUSIONS: Discrepancies between the patient discharge medication list and the medication information in the discharge letter for the primary care physician occur frequently. This may be an important source of medication errors, as confusion and uncertainty about the correct discharge medications can originate from these discrepancies. Increasing numbers of drugs involve a higher risk for discrepancies. Medication reconciliation between both lists is warranted to avoid medication errors.

Effect of medication reconciliation at hospital admission on medication discrepancies during hospitalization and at discharge for geriatric patients.

BACKGROUND: Medication discrepancies have the potential to cause harm. Medication reconciliation by clinical pharmacists aims to prevent discrepancies and other drug-related problems. OBJECTIVE: To determine how often discrepancies in the physician-acquired medication history result in discrepancies during hospitalization and at discharge. Secondary objectives were to determine the influence of clinical pharmacists' interventions on discrepancies and to investigate possible patient-related determinants for experiencing discrepancies. METHODS: This was a retrospective, single-center, cohort study of patients who were admitted to the acute geriatric department of a Belgian university hospital and followed up by clinical pharmacists between September 2009 and April 2010. Patients were limited to those 65 years or older who were taking 1 or more prescription drug. Medication reconciliation at admission, during hospitalization, and at discharge was conducted by an independent pharmacist who gathered information via chart reviews. RESULTS: The reconciliation process at admission identified 681 discrepancies in 199 patients. Approximately 81.9% (163) of patients had at least 1 discrepancy in the physician-acquired medication history. The clinical pharmacists performed 386 interventions, which were accepted in 279 cases (72.3%). A quarter of the medication history discrepancies (165; 24.2%) resulted in discrepancies during hospitalization, mostly because the intervention was not accepted. At discharge, 278 medication history discrepancies (40.8%) resulted in discrepancies in the discharge letter, accounting for 50.2% of all 554 discrepancies identified in the discharge letters. The likelihood for experiencing discrepancies at admission increased by 47% for every additional drug listed in the medication history. CONCLUSIONS: Discrepancies in the physician-acquired medication history at admission do not always correlate with discrepancies during hospitalization because of clinical pharmacists' interventions; however, discrepancies at admission may be associated with at least half of the discrepancies at discharge. Clinical pharmacist-conducted medication reconciliation can reduce these discrepancies, provided the erroneous information in the physician-acquired medication history is corrected and each intentional change in the medication plan is well documented during hospitalization and at discharge.

The process of decline in advanced activities of daily living: a qualitative explorative study in mild cognitive impairment.

BACKGROUND: The notion of "minimal impairment in instrumental activities of daily living (i-ADL)" is important in the diagnosis of mild cognitive impairment (MCI), but is presently not adequately operationalized. ADL is stratified according to difficulty, complexity, and also to vulnerability to early cognitive changes in a threefold hierarchy: basic activities of daily living (b-ADL), i-ADL, and advanced activities of daily living (a-ADL). This study aims to gain a deeper understanding of the functional decline in the process of MCI. METHODS: In a qualitative design, 37 consecutive patients diagnosed with amnestic (a)-MCI and their proxies were interviewed at two geriatric day hospitals. Constant comparative analysis was used for the analysis. RESULTS: The a-ADL-concept emerged as important in the diagnosis of MCI. All participants were engaged in a wide range of activities, which could be clustered according to the International Classification of Functioning, Disability and Health (ICF). Participants reported subtle difficulties in performance. A process of functional decline was identified in which adaptation and coping mechanisms interacted with the process of reduced skills, leading to an activity disruption and an insufficiency in functioning. CONCLUSION: This study asserts the inclusion of an evaluation of a-ADL in the assessment of older persons. When evaluating ADL at three levels (b-ADL, i-ADL, and a-ADL), all the activities one can perform in daily living are covered.

Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem bark in human adult volunteers with diagnosed uncomplicated falciparum malaria. Part 2: a clinical phase IIB trial.

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.

Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem bark in human adult volunteers with diagnosed uncomplicated falciparum malaria. Part 1: a clinical phase IIA trial.

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.

Circulating heat shock protein 70 in health, aging and disease.

BACKGROUND: Heat shock proteins (Hsp) are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters. RESULTS: Serum Hsp70, Interleukin (IL) -10, IL-6 and Tumor Necrosis Factor (TNF) alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years) and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years). In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L) showed significantly (p = 0.007) higher Hsp70 values; and Hsp70 correlated positively (p < 0.001) with IL-6 and CRP, but not with TNF-alpha or IL-10. A significant association was also noted between Hsp70 levels and the degree of dependency and cognitive decline in geriatric patients. CONCLUSIONS: The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.

The appropriate use of non-steroidal anti-inflammatory drugs in rheumatic disease: opinions of a multidisciplinary European expert panel.

INTRODUCTION: Given the safety issues of non-steroidal anti-inflammatory drugs (NSAID) and the robustness of guidelines, making treatment choices in daily clinical practice is increasingly difficult. This study aimed systematically to analyse the opinions of a multidisciplinary European expert panel on the appropriateness of different NSAID, with or without the use of a proton pump inhibitor (PPI), in individual patients with chronic rheumatic disease. METHODS: /Using the Research and Development/University of California at Los Angeles appropriateness method, the appropriateness of five (non-)selective NSAID with or without a PPI was assessed for 144 hypothetical patient profiles, ie, unique combinations of cardiovascular and gastrointestinal risk factors. Appropriateness statements were calculated for all indications. RESULTS: All options without PPI were considered appropriate in patients with no gastrointestinal/cardiovascular risk factors. Cyclooxygenase-2 selective inhibitors (C2SI) alone and non-selective NSAID plus PPI were preferred for patients with elevated gastrointestinal risk and low cardiovascular risk. Naproxen plus PPI was favoured in patients with high cardiovascular risk. For the combination of high gastrointestinal/high cardiovascular risk the use of any NSAID was discouraged; if needed, naproxen plus PPI or a C2SI plus PPI could be considered. DISCUSSION: The panel results may support treatment considerations at the level of individual patients, according to their gastrointestinal/cardiovascular risk profile.

Assessment of the short-term safety and tolerability of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii (PR 259 CT1) in healthy volunteers: a clinical phase I study.

The aim of this study was to evaluate the short-term safety and tolerability of an antimalarial herbal medicinal product (PR 259 CT1) consisting of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii when given orally to healthy adult male volunteers. The amount of the major alkaloid strictosamide in the extract was determined by a validated HPLC method and was shown to be 5.6 %. The herbal preparation was formulated in a gelatine capsule form containing 500 mg of PCR 259 CT1. A sample of 15 healthy male volunteers, selected using the Lot Quality Assurance of Sampling (LQAS) method, was eligible for inclusion after fulfillment of the inclusion criteria and clinical examination by a physician. The volunteers were treated in an outpatient clinic with a drug regimen of two 500 mg capsules three times daily (each eight hours) for seven days, during meals. Safety and tolerability were monitored clinically, haematologically, biochemically and by electrocardiographic (ECG) examination at days 0, 1, 3, 7 and 14. Adverse effects were recorded by self-reporting of the participants or by detection of abnormalities in clinical examinations by a physician. The oral administration of PR 259 CT1 at high doses of 2 × 500 mg/capsule/day for 7 days was found to induce no significant changes in the concentration levels of all investigated haematological, biochemical, electrocardiogram and vital sign parameters and physical characteristics after 14 days of treatment compared to those seen in the baseline data. The concentration levels of all evaluated parameters were within the normal limits as reported in the literature. All adverse events noted were mild and self-resolving including increase of appetite (33 %), headache (20 %) and nausea (20 %). Other minor side effects were insomnia, somnolence and asthenia (7 %). Thus, PR 259 CT1 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II clinical trial.

Effects on muscle performance of NSAID treatment with piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. A double blind randomized controlled trial.

BACKGROUND: Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp. METHODS: Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation. RESULTS: EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group. CONCLUSIONS: Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN96340690.

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.