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Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline. During this process, total physiological reserves decrease and become less likely to be sufficient for the maintenance and repair of the ageing body. Central to the clinical concept of frailty is that no single altered system alone defines it, but that multiple systems are involved. Clinical consensus regarding the phenotype which constitutes frailty, drawing upon the opinions of numerous authors, shows the characteristics to include wasting (loss of both muscle mass and strength and weight loss), loss of endurance, decreased balance and mobility, slowed performance, relative inactivity and, potentially, decreased cognitive function. Frailty is a distinct entity easily recognized by clinicians, with multiple manifestations and with no single symptom being sufficient or essential in its presentation. Manifestations include appearance (consistent or not with age), nutritional status (thin, weight loss), subjective health rating (health perception), performance (cognition, fatigue), sensory/physical impairments (vision, hearing, strength) and current care (medication, hospital). Although the early stages of the frailty process may be clinically silent, when depleted reserves reach an aggregate threshold leading to serious vulnerability, the syndrome may become detectable by looking at clinical, functional, behavioral and biological markers. Thus, a better understanding of these clinical changes and their underlying mechanisms, beginning in the pre-frail state, may confirm the impression held by many geriatricians that increasing frailty is distinguishable from ageing and in consequence is potentially reversible. We therefore provide an update of the physiopathology and clinical and biological characteristics of the frailty process and speculate on possible preventative approaches.

Vitamin D is increasingly thought to play a role in regulating immunity. This comprehensive review updates the current understanding regarding ways in which we believe that vitamin D regulates responsiveness of the immune system and how serum status modulates the host defense against pathogens. The literature was searched by using PubMed and Scopus with the following key words: vitamin D, immunity, innate and adaptive immunity, infectious disease, and vaccine response. Vitamin D deficiency remains a major public health concern worldwide. The overall body of evidence confirms that vitamin D plays an important role in modulating the immune response to infections. Epidemiologic studies suggest a clear association between vitamin D deficiency and susceptibility to various pathogens. However, translation of vitamin D use into the clinic as a means of controlling infections is fraught with methodologic and epidemiologic challenges. The recent discovery of alternative activation pathways, different active forms of vitamin D, and possible interaction with non–vitamin D receptors provide further complications to an already complex interaction between vitamin D and the immune system. Moreover, it has become apparent that the individual responsiveness to supplementation is more dynamic than presumed from the static assessment of 25-hydroxy vitamin D status. Furthermore, the epigenetic response at the level of the individual to environmental changes and lifestyle or health conditions provides greater variation than those resulting from vitamin D receptor polymorphisms. To understand the future of vitamin D with respect to clinical applications in the prevention and better control of infectious diseases, it is necessary to determine all aspects of vitamin D metabolism, as well as the mechanisms by which active forms interact with the immune system globally. For the most part, we are unable to identify tissue-specific applications of supplementation except for those subjects at high risk of osteomalacia and osteoporosis.

Geriatric pharmacotherapy represents one of the biggest achievements of modern medical interventions. However, geriatric pharmacotherapy is a complex process that encompasses not only drug prescribing but also age-appropriate drug development and manufacturing, appropriate drug testing in clinical trials, rational and safe prescribing, reliable administration and assessment of drug effects, including adherence measurement and age-appropriate outcomes monitoring. During this complex process, errors can occur at any stage, and intervention strategies to improve geriatric pharmacotherapy are targeted at improving the regulatory processes of drug testing, reducing inappropriate prescribing, preventing beneficial drug underuse and use of potentially harmful drugs, and preventing adverse drug interactions. The aim of this review is to provide an update on selected recent developments in geriatric pharmacotherapy, including age discrimination in drug trials, a new healthcare professional qualification and shared competence in geriatric drug therapy, the usefulness of information and communication technologies, and pharmacogenetics. We also review optimizing strategies aimed at medication adherence focusing on complex elderly patients. Among the current information technologies, there is sufficient evidence that computerized decision-making support systems are modestly but significantly effective in reducing inappropriate prescribing and adverse drug events across healthcare settings. The majority of interventions target physicians, for whom the scientific concept of appropriate prescribing and the acceptability of the alert system used play crucial roles in the intervention’s success. For prescribing optimization, results of educational intervention strategies were inconsistent. The more promising strategies involved pharmacists or multidisciplinary teams including geriatric medicine services. However, methodological weaknesses including population and intervention heterogeneity do not allow for comprehensive meta-analyses to determine the clinical value of individual approaches. In relation to drug adherence, a recent meta-analysis of 33 randomized clinical trials in older patients found behavioural interventions had significant effects, and these interventions were more effective than educational interventions. For patients with multiple conditions and polypharmacy, successful interventions included structured medication review, medication regimen simplification, administration aids and medication reminders, but no firm conclusion in favour of any particular intervention could be made. Interventions to optimize geriatric pharmacotherapy focused most commonly on pharmacological outcomes (drug appropriateness, adverse drug events, adherence), providing only limited information about clinical outcomes in terms of health status, morbidity, functionality and overall healthcare costs. Little attention was given to psychosocial and behavioural aspects of pharmacotherapy. There is sufficient potential for improvements in geriatric pharmacotherapy in terms of drug safety and effectiveness. However, just as we require evidence-based, age-specific, pharmacological information for efficient clinical decision making, we need solid evidence for strategies that consistently improve the quality of pharmacological treatments at the health system level to shape ‘age-attuned’ health and drug policy.

Current vaccination policy in most high-income countries aims to counteract the decline in cell-mediated immunity to varicella zoster virus that occurs with advancing age or immunosuppression. The aim of this review was to describe the burden of illness associated with herpes zoster (HZ) and post-herpetic neuralgia (PHN) risks and their impact on the social and common life in infected people. The effectiveness/efficacy and cost effectiveness of the immunization strategy will be presented through the review of the literature relevant to the live attenuated HZ vaccine (ZLV) licensed in 2006 and the recombinant HZ vaccine (RZV). The latter has very recently been approved to protect aged people aged ≥ 50 years against HZ morbidity including its complications, and associated health-care costs. Finally, this review also provides data with respect of precautions of using and safety of ZVL and RVZ.

Vitamins and trace elements are essential to the body, however, deficiencies are frequently observed in the general population. Diet is mostly responsible for these deficiencies but drugs also may play a significant role by influencing their metabolism. These effects are rarely assessed in clinical practice, in part because of limited data available in the literature. Drug-induced micronutrient depletions, however, may be the origin of otherwise unexplained symptoms that might sometimes influence medication compliance. We present various examples of widely prescribed drugs that can precipitate micronutrient deficiencies. This review aims at sensitizing physicians on drug–micronutrient interactions. High-risk population groups also are presented and supplementation protocols are suggested.

Introduction Pharmaceutical interventions can reduce negative outcomes related to potentially inappropriate prescriptions (PIPs). Objective The objective of this study was to compare the impact of interventions on the reduction of PIPs and on different clinical outcomes using two electronic explicit tools. Methods A randomized controlled trial was conducted in patients hospitalized between 2018 and 2019 at the Acute Care for Elders unit at Lausanne University Hospital in Switzerland. A medication review was conducted using PIM-Check in the first arm and STOPP/START in the second arm. Proposed interventions were communicated to the physicians. Clinical outcomes evaluated were incidence of falls, delirium, activities of daily living (ADL), length of stay, number of drugs at discharge and hospital readmission. Results The 123 included patients (60 in the first arm and 63 in the second arm) were 86.3 ± 6.6 years old, had 3.5 ± 1.7 diseases and were treated by 6.2 ± 2.7 drugs at admission. There was a significant decrease in PIPs in each arm, but no significant difference between arms. The deprescription of nervous system drugs was significantly higher with STOPP/START than with PIM-Check (Chi-square p  = 0.025). ADL scores between home and discharge were significantly higher in the STOPP/START arm than in the PIM-Check arm (4.42 vs 3.77; p  = 0.040). The predictors of ADL score improvement were the deprescription of nervous system drugs ( β  = 0.423; 95% CI 0.034–0.812; p  = 0.033), the use of STOPP/START ( β  = 0.798, 95% CI 0.305–1.290; p  = 0.002) and a shorter length of hospital stay ( β  = −0.033, 95% CI − 0.056 to − 0.010; p  = 0.005). Conclusions Although PIM-Check was non-inferior to STOPP/START in reducing the number of PIPs, STOPP/START had a significantly higher impact on ADL. The use of STOPP/START or the deprescription of two nervous system drugs would allow the patient to acquire almost one more basic function of living. On the other hand, a loss of one point on the ADL score was observed per month of hospitalization. Clinical Trials Registration Number NCT04028583.

Advanced age is one indicator of likely immune dysfunction. As worldwide, the global population contains progressively more and more older individuals there is likelihood of an increased prevalence and incidence of infectious diseases due to common and emergent pathogens. The resultant increase in mortality and morbidity would be matched by the risk of functional decline and disability. Maintaining immune function at a plateau throughout life may therefore be associated with considerable cost savings. The aim of improving immune function in older individuals may be achieved through considering a therapeutic approach to rejuvenate, stimulate or support the indigenous immune system to perform in a more optimal manner. In terms of cost effectiveness a therapeutic approach may prove difficult because of issues associated with; identifying those who would benefit the most from this treatment, identifying the type of treatment which would suit them and identifying whether the treatment was successful. The alternative of supporting or providing a stronger stimulus through vaccination, whilst more cost effective, may be a more valuable option in the short term. Both approaches will be addressed in this review.

PurposePotentially inappropriate prescribing (PIP) is a source of preventable adverse drug events. The objective of this study was a comparative analysis (quantitative and qualitative) between two tools used to detect PIP, PIM-Check and STOPP/START.MethodsFirst, a qualitative analysis (QAC) was conducted to evaluate the concordance between the criteria, which constitute PIM-Check and the gold standard STOPP/START. Second, a retrospective comparative and observational study was performed on the list of treatment at the admission of 50 older patients hospitalized in an acute geriatric ward of a university hospital in Switzerland in 2016 using both tools.ResultsThe QAC has shown that 50% (57 criteria) of STOPP/START criteria are fully or partially concordant with those of PIM-Check. The retrospective study was performed on 50 patients aged 87 years, suffering from 5 co-morbidities (min–max 1–11) and treated by of 8 drugs (min–max 2–16), as medians. The prevalence of the detected PIP was 80% by PIM-Check and 90% by STOPP/START. Medication review shows that 4.2 PIP per patient were detected by PIM-Check and 3.5 PIP by STOPP/START among which 1.9 PIP was commonly detected by both tools, as means. PIM-Check detected more PIP related to cardiology, angiology, nephrology, and endocrinology in older patients but missed the PIP related to geriatric syndromes (e.g., fall, dementia, Alzheimer) detected by STOPP/START.ConclusionsBy using PIM-Check in geriatric settings, some PIP will not be detected. It is considered as a limitation for this tool in this frail population but brings a certain complementarity in other areas of therapy not covered by STOPP/START.

Purpose Potentially inappropriate prescribing is common in older people presenting to hospital with acute illness in Ireland. The aim of this study was to determine if this phenomenon is unique to Ireland or whether it is a more widespread problem in hospitals across Europe. Methods Prospective data were collected from 900 consecutive older patients admitted to six university teaching hospitals (150 patients per centre) in Geneva (Switzerland), Madrid (Spain), Oostende (Belgium), Perugia (Italy), Prague (Czech Republic) and Cork (Ireland). Age, gender, comorbidity, cognitive status, prescription medicines taken before admission and baseline haematological, biochemical and electrocardiographic data were recorded. STOPP and Beers’ criteria were applied to detect potentially inappropriate medicines (PIMs). START criteria were applied to detect potentially inappropriate prescribing omissions (PPOs). Results The overall PIM prevalence rate was 51.3% using STOPP criteria, varying from 34.7% in Prague to 77.3% in Geneva, and 30.4% using Beer’s criteria, varying from 22.7% in Prague to 43.3% in Geneva. Using START criteria, the overall PPO prevalence rate was 59.4%, ranging from 51.3% in Cork to 72.7% in Perugia. Polypharmacy predicted the presence of PIMs using STOPP criteria [with >10 medications: odds ratio (OR)  7.22, 95% confidence interval (CI) 4.30–12.12, p  < 0.001] and Beers’ criteria (with >10 medications: OR 4.87, 95% CI 3.00–7.90, p  < 0.001). Increasing co-morbidity (Charlson Index ≥2) and age ≥85 years significantly predicted PPOs. Conclusion Potentially inappropriate drug prescribing and the omission of beneficial drugs are highly prevalent in acutely ill hospitalized older people in six European centres.

Background Evidence suggests that aerobic-type training confers physical benefits and appears to contribute positively to brain health. This study aims to compare the effect of 9-weeks continuous (CAT) to interval aerobic training (IAT) on brain derived neurotrophic factor (BDNF) plasma level, aerobic fitness, cognitive performance, and quality of life among senior with Alzheimer’s disease (AD). Methods 52 participants were randomly allocated into three groups (CAT n  = 14; IAT n  = 17; and Controls n  = 21). CAT and IAT consisted of 18 sessions of 30-min cycling, twice a week, over 9 weeks. During the same period, controls were engaged in interactive information sessions. Plasma BDNF level; aerobic fitness parameters (Metabolic equivalent task - METs; Maximal Tolerated Power – MTP); functional capacities (6-Minute Walk Test - 6MWT); cognitive performance (Mini Mental State Examination; Rey auditory verbal learning test; and digit span test) and quality of life (Quality Of Life of Alzheimer’s Disease scale - QoL-AD) were measured in all participants at baseline and 9 weeks later. A third plasma BDNF level was quantified following a 4 weeks detraining. Results No significant change was measured in terms of plasma BDNF level and cognitive performance after interventions, in all groups compared to baseline. After 9 weeks, CAT and IAT significantly improved aerobic fitness parameters compared to controls (METs: + 0.6 and + 1.0 vs. + 0.4; MTP: + 16 watts and + 20 watts vs. + 10 watts; and functional capacities (6MWT: + 22 m and + 31 m vs. -40 m). Compared to controls, QoL-AD after CAT was improved (+ 2 points; p = 0.02 ). Conclusions Neither aerobic exercise modalities significantly modified plasma BDNF levels and cognitive performances. CAT and IAT enhanced aerobic fitness and functional capacities in AD patients and CAT their QoL. Trial registration ClinicalTrials.gov website (NCT02968875); registration date: 7 September 2016. “Retrospectively registered”.