[Prevention of frailty]. / Prävention der Frailty.

BACKGROUND: The presence of frailty in older patients increases the risk for adverse health events and for a loss of independence. Measures for the prevention of this geriatric syndrome should be incorporated into routine healthcare. OBJECTIVE: What types of interventions could be effective in the prevention of frailty and how can preventive strategies be successfully implemented? METHOD: Narrative review article. RESULTS: The concept of frailty is multidimensional and potential starting points for a prevention of frailty can be found within different dimensions (e.g., dimensions of physical activity and nutrition, psychosocial dimension). Epidemiological analyses have identified factors that increase or decrease the risk for becoming frail. Evidence from randomized controlled trials that examined the effectiveness of specific interventions in the prevention of frailty is still limited. Based on the available data, interventions using physical exercise appear to be effective in preventing frailty. In primary care in Germany the frailty status of older patients is not yet routinely recorded, which impedes the identification of patients at risk (patients with pre-frailty) and the implementation of targeted preventive strategies. The Integrated Care for Older People (ICOPE) concept of the World Health Organization offers a potential approach to prevent frailty and to promote healthy ageing within the population. CONCLUSION: The prevention of frailty is possible and reasonable. Comprehensive and targeted preventive strategies are yet to be implemented.

[Clinical importance of the detection of frailty]. / Klinische Bedeutung der Erfassung von Frailty.

Frailty is a multidimensional geriatric syndrome characterized by the loss of the individual reserve capacity and increased vulnerability to internal and external stressors. Frailty in older adults is associated with an increased risk for falls and loss of autonomy as well as an increased mortality. The identification of patients who suffer from frailty can trigger a comprehensive geriatric assessment and justify targeted treatment options. Furthermore, by the detection of frailty each patient with an increased risk of an unfavorable treatment outcome can be identified. There are a confusing number of instruments available for the detection of frailty but only a limited number of these instruments are available in a German version. The choice of an appropriate instrument is largely dependent on the clinical setting and the available resources.

Evidence gap on antihyperglycemic pharmacotherapy in frail older adults : A systematic review.

BACKGROUND: Although antihyperglycemic pharmacotherapy in frail older adults with type 2 diabetes mellitus (T2DM) is challenging, recommendations from international guidelines are mainly based on indirect evidence from trials not including frail participants. OBJECTIVE: This systematic review investigated the effectiveness and safety of pharmacotherapy in frail older adults with T2DM. MATERIAL AND METHODS: Randomized (RCT) and non-randomized prospective clinical trials (non-RCT) were searched in three electronic databases (Medline, Embase, Central) up to October 2018. Trials in older adults with T2DM who were assessed as significantly or severely impaired by defined cut-off scores of assessment instruments on frailty, activities of daily living or physical functional impairment were included. RESULTS: Two reviewers independently screened 17,391 references for inclusion and assessed risk of bias with ROBINS­I. Five non-RCTs and no RCT were identified. Treatment of T2DM without insulin compared to insulin could be associated with increased improvement in cardiac functions in patients with cardiac resynchronization therapy and with decreased falls in frail older women. While better glycemic control with low variability and low HbA1c (hemoglobin A1c) values (<7%) was associated with better maintenance of physical function in community-dwelling older persons, higher HbA1c values (8-8.9%) were associated with a reduction in the composite outcome of death or functional decline in community-dwelling diabetic older adults with need for skilled assistance. Due to serious risk of bias in all studies, results should be considered with caution. CONCLUSION: Well-designed, large-scale RCTs including this important group of patients are required to assess the effectiveness and safety of pharmacotherapy and HbA1c targets.

[Frailty: Concept and Diagnosis]. / Frailty: Konzept und Diagnose.

Frailty increases the older adult's vulnerability to suffer adverse health outcomes. To date, no gold standard for the diagnosis of frailty exists. This article provides an overview of the most relevant frailty instruments and their scope of application.

[Therapy of physical frailty]. / Therapie der physischen Frailty.

As an overarching geriatric syndrome, frailty describes a potentially reversible transitional stage between functional autonomy and irreversible disability. Thus, frailty addresses a "window of opportunity" in which functional limitations can be successfully treated. This article provides an overview of the therapeutic approaches and their scientific evidence.

Interventions to prevent the onset of frailty in adults aged 60 and older (PRAE-Frail): a systematic review and network meta-analysis.

PURPOSE: Frailty in older adults is associated with multiple adverse health outcomes, while evidence on its successful prevention has been scarce. Therefore, we analyzed the effectiveness of different interventions for the prevention of frailty onset. METHODS: In this systematic review, eight databases were searched for randomized controlled trials of interventions in non-frail (i.e., robust or pre-frail) adults aged ≥ 60 years that assessed frailty incidence at follow-up. Additive component network meta-analysis (CNMA) was conducted to isolate the effect of different intervention types on the main outcome of frailty incidence, reporting relative risk (RR) with 95% confidence intervals (CI). The effect on gait speed was analyzed as an additional outcome using a classic network meta-analysis and the standardized mean difference (SMD) with 95% CI. RESULTS: We screened 24,263 records and identified 11 eligible trials. Nine trials (842 participants, all categorized according to the physical phenotype) in pre-frail (seven RCTs) and robust/pre-frail (two RCTs) older adults were included in the CNMA. Physical exercise significantly reduced frailty incidence at follow-up (RR 0.26, 95% CI 0.08; 0.83), while this was not found for nutritional interventions (RR 1.16, 95% CI 0.33; 4.10). Interventions based on physical exercise also improved gait speed (SMD 1.55, 95% CI 1.16; 1.95). In addition, 22 eligible trial protocols without published results were identified. CONCLUSION: Interventions based on physical exercise appear to be effective in preventing the onset of frailty in older adults. Although the available data are still limited, results from ongoing trials may add to the body of evidence in the foreseeable future.

Development and Pilot Testing of an Algorithm-Based Approach to Anticholinergic Deprescribing in Older Patients.

BACKGROUND: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing. METHODS: Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.g., by recommending alternative drugs with lower risk, were developed. An accompanying test battery was assembled by focusing on instruments that sensitively reflect anticholinergic load and may be sensitive to depict changes (Neuropsychological Assessment Battery to measure memory and attention, validated assessments for constipation, urinary symptoms, and xerostomia, as well as blood biomarkers). The approach was pilot-tested in a geriatric rehabilitation unit, with clinician feedback as the primary outcome and characterization of anticholinergic symptoms as the secondary outcome. The intervention was delivered by a pharmacist and a clinical pharmacologist who used the algorithms to generate personalized recommendation letters. RESULTS: We included a total of 20 patients, 13 with anticholinergic drugs and 7 without. Recommendations were made for 22 drugs in nine patients from the intervention group, of which seven letters (78%) were considered helpful and 8/22 (36%) anticholinergic drugs were discontinued, reducing anticholinergic load in seven patients. In contrast to patients without drug change, memory assessment in patients with reduced anticholinergic load improved significantly after 2 weeks (6 ± 3 vs. -1 ± 6 points). CONCLUSIONS: The approach was well received by the participating physicians and might support standardized anticholinergic deprescribing.

Validation of a telephone-based administration of the simplified nutritional appetite questionnaire.

BACKGROUND: Anorexia of aging is characterized by an age-associated reduction of appetite, whose aetiology in most cases is multifactorial and which often triggers malnutrition. The Simplified Nutritional Appetite Questionnaire (SNAQ) is an established screening tool. This study aimed to investigate reliability, validity, and feasibility of its telephone administration (T-SNAQ) in German community-dwelling older adults. METHODS: This cross-sectional single-centre study recruited participants from April 2021 to September 2021. First, the SNAQ was translated into German according to an established methodology. After translation, reliability, construct validity, and feasibility of the T-SNAQ were analysed. A convenience sample of community-dwelling older adults aged ≥70 years was recruited. The following measurements were applied to all participants: T-SNAQ, Mini Nutritional Assessment - Short Form (MNA-SF), six-item Katz index of independence in activities of daily living (ADL), eight-item Lawton instrumental activities of daily living (IADL), telephone Montreal Cognitive Assessment (T-MoCA); FRAIL scale, Geriatric Depression Scale (GDS-15) and Charlson co-morbidity index as well as daily caloric and protein intake. RESULTS: One hundred twenty participants (59.2% female) with a mean age of 78.0 ± 5.8 years were included in the present study. The percentage of participants identified with poor appetite based on T-SNAQ was 20.8% (n = 25). T-SNAQ showed a good internal reliability with a Cronbach's alpha coefficient of 0.64 and a good test-retest reliability [intraclass coefficient of 0.95 (P < 0.05)]. Regarding construct validity, T-SNAQ was significantly positively correlated with MNA-SF (r = 0.213), T-MoCA (r = 0.225), daily energy (r = 0.222) and protein intake (r = 0.252) (P < 0.05). It also demonstrated a significant negative association with GDS-15 (r = -0.361), FRAIL scale (r = -0.203) and Charlson co-morbidity index (r = -0.272). Regarding applicability, the mean time for T-SNAQ was 95 s and completion rate was 100%. CONCLUSIONS: The T-SNAQ is a feasible screening instrument for anorexia of aging in community-dwelling older adults via telephone interviews.

Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study.

BACKGROUND: Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure. OBJECTIVE: We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients. METHODS: The frailty status of adults aged ≥ 70 years receiving regular direct oral anticoagulant medication was assessed by four different instruments: Fried physical phenotype, Rockwood frailty index, Short Physical Performance Battery, and FRAIL scale. The two performance measures "slow gait speed" and "weak grip strength" were used to build a separate score depending on the number of positive criteria (none, one, two). For each participant, a single steady-state direct oral anticoagulant trough plasma concentration was collected, dose-normalized, and its relationship to the various frailty assessments analyzed. RESULTS: Forty-two participants completed the study, with most using apixaban (n = 22). Dose-normalized apixaban trough concentrations were 2.48-fold higher in frail participants (Fried phenotype) than in robust participants (p = 0.009) and correlated positively with Fried physical phenotype (rs = 0.535, p = 0.010) and negatively with Short Physical Performance Battery (rs = - 0.434, p = 0.044). Compared with participants who met none of the criteria "slow gait speed" and "weak grip strength", apixaban trough concentrations were approximately 1.9-fold higher in participants who were positive for one (p = 0.018) or two (p = 0.013) of these measures. CONCLUSIONS: In this exploratory study, higher levels of frailty on performance-based frailty assessments were associated with higher apixaban exposure in older adults. CLINICAL TRIAL REGISTRATION: German Clinical Trials Register DRKS00016741; registered 20 February, 2019.

Optimizing pharmacotherapy and deprescribing strategies in older adults living with multimorbidity and polypharmacy: EuGMS SIG on pharmacology position paper.

Inappropriate polypharmacy is highly prevalent among older adults and presents a significant healthcare concern. Conducting medication reviews and implementing deprescribing strategies in multimorbid older adults with polypharmacy are an inherently complex and challenging task. Recognizing this, the Special Interest Group on Pharmacology of the European Geriatric Medicine Society has compiled evidence on medication review and deprescribing in older adults and has formulated recommendations to enhance appropriate prescribing practices. The current evidence supports the need for a comprehensive and widespread transformation in education, guidelines, research, advocacy, and policy to improve the management of polypharmacy in older individuals. Furthermore, incorporating deprescribing as a routine aspect of care for the ageing population is crucial. We emphasize the importance of involving geriatricians and experts in geriatric pharmacology in driving, and actively participating in this transformative process. By doing so, we can work towards achieving optimal medication use and enhancing the well-being of older adults in the generations to come.

Drug Treatment of Hypercholesterolemia in Older Adults: Focus on Newer Agents.

There is increasing research interest in cholesterol-lowering therapy in older patients. The newer lipid-lowering agents (the proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors evolocumab and alirocumab; the PCSK9 synthesis inhibitor inclisiran, and the adenosine triphosphate-citrate lyase inhibitor bempedoic acid) might also provide more options for the future treatment of older patients. Data analyses of the phase III outcome trials of the PCSK9 inhibitors suggest that their clinical benefits are maintained at older ages and that there is no increased relative risk of adverse events in older patients; however, data from patients aged ≥ 75 years and particularly aged ≥ 85 years are limited, and the trials did not collect information on the frailty status of patients. Frailty is a predictor of adverse outcomes, including mortality, and might help guide therapy decisions. To date, no outcome data are available for cardiovascular endpoints for the low-density lipoprotein cholesterol-lowering drugs inclisiran and bempedoic acid. Except for the risk of gout and tendon rupture with bempedoic acid, which remains to be further characterized in larger populations, the safety profile of the novel lipid-lowering agents in older patients seems favorable. The newer lipid-lowering agents could be added to other lipid-lowering medication or used as an alternative treatment in older patients with documented statin intolerance (as is already recommended in guidelines for the PCSK9 inhibitors), such as myopathy. Especially in older patients needing high-intensity therapy despite polypharmacy or certain comedications, the absence of clinically relevant drug-drug interactions with the PCSK9 inhibitors and inclisiran might be an advantage.

Development of an Electronic Tool to Assess Patient Preferences in Geriatric Polypharmacy (PolyPref).

Purpose: Medical decision-making in older adults with multiple chronic conditions and polypharmacy should include the individual patient's treatment preferences. We developed and pilot-tested an electronic instrument (PolyPref) to elicit patient preferences in geriatric polypharmacy. Patients and Methods: PolyPref follows a two-stage direct approach to preference assessment. Stage 1 generates an individual preselection of relevant health outcomes and medication regimen characteristics, followed by stage 2, in which their importance is assessed using the Q-sort methodology. The feasibility of the instrument was tested in adults aged ≥70 years with ≥2 chronic conditions and regular intake of ≥5 medicines. After the assessment with PolyPref, the patients rated the tool with regard to its comprehensibility and usability and assessed the accuracy of the personal result. Evaluators rated the patients' understanding of the task. Results: Eighteen short-term health outcomes, 3 long-term health outcomes, and 8 medication regimen characteristics were included in the instrument. The final population for the pilot study comprised 15 inpatients at a clinic for geriatric rehabilitation with a mean age of 80.6 (± 6.0) years, a median score of 28 (range 25-30) points on the Mini-Mental State Examination, and a mean of 11.6 (± 3.6) regularly taken medicines. Feedback by the patients and the evaluators revealed ratings in favor of understanding and comprehensibility of 86.7% to 100%. The majority of the patients stated that their final result summarized the most important aspects of their pharmacotherapy (93.3%) and that its ranking order reflected their personal opinion (100%). Preference assessment took an average of 35 (± 8.5) min, with the instrument being handled by the evaluator in 14 of the 15 participants. Conclusion: Preference assessment with PolyPref was feasible in older adults with multiple chronic conditions and polypharmacy, offering a new strategy for the standardized evaluation of patient priorities in geriatric pharmacotherapy.

Validation of a proxy-reported SARC-F questionnaire for current and retrospective screening of sarcopenia-related functional impairments.

BACKGROUND: The strength, assistance walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire is a well-established instrument for screening of sarcopenia and sarcopenia-related functional impairments. As it is based on self-reporting, its use precludes patients who are unable to answer the questionnaire as a consequence of severe acute diseases or cognitive impairment. Therefore, we aimed to validate a proxy-reported version of the SARC-F for both ad-hoc as well as retrospective screening for severe sarcopenia-related functional impairments. METHODS: Patients aged ≥60 years completed the SARC-F and performed the short physical performance battery (SPPB) at baseline (T1). Proxies in Cohort A gave a simultaneous assessment of the patients' functional status with the proxy-reported SARC-F at T1 and again, retrospectively, after 3 months (T2). Proxies in Cohort B only completed the SARC-F retrospectively at T2. The questionnaires' performances were assessed through sensitivity/specificity analyses and receiver operating characteristic (ROC) curves. For non-inferiority analyses, results of both the patient-reported and proxy-reported SARC-F were correlated with the SPPB total score as well as the results of the chair-rise test subcategory; the respective correlation coefficients were tested against each other. RESULTS: One hundred and four patients and 135 proxies participated. Using a SPPB score < 9 points as the reference standard, the proxy-reported SARC-F identified patients at high risk for sarcopenia-related functional impairment with a sensitivity of 0.81 (ad-hoc), 0.88 (retrospective Cohort A), and 0.87 (retrospective Cohort B) as well as a specificity of 0.89 (ad-hoc), 0.78 (retrospective Cohort A), and 0.64 (retrospective Cohort B). Areas under the ROC curves were ≥ 0.9 for the ad-hoc proxy-reported SARC-F and the retrospective proxy-reported SARC-F in both cohorts. The proxy-reported SARC-F showed a non-inferior correlation with the SPPB compared with the patient-reported SARC-F for ad-hoc (P = <0.001) as well as retrospective screening for severe sarcopenia-related functional impairment in both Cohorts A (P = 0.007) and B (P = 0.026). CONCLUSIONS: Proxy-reported SARC-F is a valid instrument for both ad-hoc as well as retrospective screening for sarcopenia-related functional impairment and could become the standard tool for evaluating this risk in older adults with severe acute disease, for example, in patients with quickly evolving haematological conditions.

Methods to Assess Patient Preferences in Old Age Pharmacotherapy - A Systematic Review.

PURPOSE: The aim of this systematic review was to identify methods used to assess medication preferences in older adults and evaluate their advantages and disadvantages with respect to their applicability to the context of multimorbidity and polypharmacy. MATERIAL AND METHODS: Three electronic databases (PubMed, Web of Science, PsycINFO) were searched. Eligible studies elicited individual treatment or outcome preferences in a context that involved long-term pharmacological treatment options. We included studies with a study population aged ≥ 65 years and/or with a mean or median age of ≥ 75 years. Qualitative studies, studies assessing preferences for only two different treatments, and studies targeting preferences for life-sustaining treatments were excluded. The identified preference measurement methods were evaluated based on four criteria (time budget, cognitive demand, variety of pharmacological aspects, and link with treatment strategies) judged to be relevant for the elicitation of patient preferences in polypharmacy. RESULTS: Sixty articles met the eligibility criteria and were included in the narrative synthesis. Fifty-five different instruments to assess patient preferences, based on 24 different elicitation methods, were identified. The most commonly applied preference measurement techniques were "medication willingness" (description of a specific medication with inquiry of the participant's willingness to take it), discrete choice experiments, Likert scale-based questionnaires, and rank prioritization. The majority of the instruments were created for disease-specific or context-specific settings. Only three instruments (Outcome Prioritization Tool, a complex intervention, "MediMol" questionnaire) dealt with the broader issue of geriatric multimorbidity. Only seven of the identified tools showed somewhat favorable characteristics for a potential use of the respective method in the context of polypharmacy. CONCLUSION: Up to now, few instruments have been specifically designed for the assessment of medication preferences in older patients with multimorbidity. To facilitate valid preference elicitation in the context of geriatric polypharmacy, future research should focus on suitable characteristics of existing techniques to develop new measurement approaches for this increasingly relevant population.