Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

Erratum to: Multicomponent, nonpharmacological delirium interventions for older inpatients : A scoping review.

Erratum to: the article "Multicomponent, nonpharmacological delirium interventions for older inpatients. A scoping review." Unfortunately, on 18.10.2019 a preliminary and incorrect version of the flowchart (Fig. 1) was published online. In the corrected and final version one additionally identified record is listed in the flowchart. The records after removal the duplicates are n = 4451 and the records that are excluded after title abstract screening are 4571. The studies included are n = 25. In addition, a further exclusion category is added after full text screening (Study not available: n = 1) and an existing exclusion category (Repeated data use of the original study) was corrected to n = 1, which can also be found in the corrected online supplement No. 2.Z Gerontol Geriat 2019 https://doi.org/10.1007/s00391-019-01627-y Please note the correct version of Fig. 1.The original article has been corrected.

Multicomponent, nonpharmacological delirium interventions for older inpatients : A scoping review.

BACKGROUND: Older people represent a risk group for acquiring or further development of delirium during hospitalization, therefore requiring suitable nonpharmacological delirium interventions. OBJECTIVE: This scoping review analyzed nonpharmacological intervention programs for older inpatients with or without cognitive decline on regular or acute geriatric wards to present the range of interventions. METHODS: A systematic literature search was conducted using scientific databases. A total of 4652 records were screened by two independent reviewers, leaving 81 eligible articles for full-text screening and 25 studies were finally included. Inclusion criteria were older patients ≥65 years in regular or acute geriatric wards and nonpharmacological multicomponent interventions. RESULTS: More than a half of the included studies (14, 56%) recruited patients with pre-existing cognitive decline as part of the study population and 12% focused exclusively on patients with cognitive decline. On average 11 intervention components were integrated in the programs and two programs included full coverage of all 18 identified components. CONCLUSION: Only few programs were described for older inpatients and even fewer regarding pre-existing cognitive decline. The low numbers of interventions and data heterogeneity restricted the assessment of outcomes; however, delirium incidence, as reported by two thirds of the studies was reduced by nonpharmacological multicomponent interventions.

Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments.

PURPOSE: Physicians often face difficulties in choosing appropriate medications for multimorbid older people. The FORTA (Fit for the Aged) classification (A: absolutely, B: beneficial, C: careful, D: don't) was proposed as a clinical tool for improving the quality of drug treatment in the aged. As an implicit tool, FORTA has been shown to aid medication optimization and improve clinical end points in the VALFORTA trial. In this prospective randomized controlled study, 207 older hospitalized patients received standard geriatric treatment and 202 patients received FORTA-guided treatment. METHODS: Here, changes of drug prescriptions at the anatomical-therapeutic-chemical system (ATC) level were evaluated separately for important diagnoses in descriptive analyses; over- and under-treatment rates were compared between groups. RESULTS: At the individual drug/drug class level related to all important diagnoses, the application of FORTA significantly improved under-treatments for 12 drugs/drug classes (e.g., ACE inhibitors to treat arterial hypertension) and over-treatments for 7 drugs/drug classes (e.g., proton pump inhibitors to treat gastroesophageal reflux disease). CONCLUSIONS: FORTA representing the first combined positive/negative labeling approach at the individual drug level aids the optimization of drug treatment in older people as detected for drugs/drug classes at the ATC level in important indications. FORTA is effective in addressing over- and under-treatments even if analyzed for smaller subgroups of VALFORTA.

VALFORTA: a randomised trial to validate the FORTA (Fit fOR The Aged) classification.

TRIAL DESIGN: to further validate the FORTA (Fit fOR The Aged) concept, a bicentric randomised, controlled trial was run in two geriatric clinics. METHODS: patients (≥65 years, ≥3 drugs or ≥60 years, ≥6 drugs) with three relevant diseases and hospitalisation for ≥5 days were randomised. In the intervention, but not the control group, a FORTA team instructed ward physicians on FORTA. FORTA is the first positive/negative listing approach labelling medications used to treat chronic illnesses in older patients from A (indispensable), B (beneficial), C (questionable) to D (avoid). The primary end point was the FORTA score: sum of medication errors classified as over-, under- and mistreatment. Consecutive patients were randomised to the intervention and control ward; outcome assessment was blinded. RESULTS: four hundred and nine patients (age 81.5 years, 64% female, hospitalisation 17.4 days) were included. The primary end point was significantly (P < 0.0001) more reduced in the intervention versus control groups (2.7 ± 2.25 versus 1 ± 1.8, mean ± SD, intergroup comparison of admission/discharge differences). Over- and under-treatment scores and use of A (increase) and D (decrease) drugs were significantly improved (P < 0.01). The total number of adverse drug reactions (ADRs) was significantly reduced by FORTA (P < 0.05, number needed to treat is 5). Activities of daily living and renal failure improved significantly (P < 0.05). Blood pressure remained constant in the intervention, but decreased significantly in the control group. CONCLUSION: applying FORTA to hospitalised geriatric patients leads to improvement of medication quality and may improve secondary clinical end points (e.g. ADRs). The concept is amenable to successful communication and implementation. Registration (DRKS-ID): DRKS00000531. FUNDING: DFG-German Research Foundation (WE 1184/15-1).

[Renal failure and drug-drug interactions]. / Bei Niereninsuffizienz auf Arzneimittel-Interaktionen achten!

Renal failure is common and comes with a steep increasing prevalence in older patients. It is a frequent aspect in multimorbidity and associated with polypharmacia. Based on available literature an overview is given concerning important drug-drug interactions and how to avoid or manage them. Among a large variety of possible interactions anticoagulation and diuretic therapy still represent the highest clinical relevance.

Outbreak of SARS-CoV-2 in a geriatric acute-care ward during summer 2023: current aspects of infection control in the postpandemic period.

Aim: Management of a SARS-CoV-2 outbreak in geriatric patients, taking into account the transition to the post-pandemic period. Methods: PCR tests were conducted to identify the scale of infection during the outbreak; no new patients were admitted to the ward until the availability of the PCR results. Based on the results and individual risk assessment, three cohorts were formed and treated as recommended by the RKI. After terminating the admissions stop, new admissions received PCR screening. Contact patients were retested on days 3 and 5. Employees carried out self-monitoring, and if symptoms developed, an antigen test was performed. Results: Nine of the 11 PCR-positive patients (6m, 5f), median age 85 years, were immunized. Eight patients were symptomatic, ten received antiviral therapy and two required intensive care. Three symptomatic employees had a positive antigen test. Patients without direct contact to the positive cases who initially tested negative and the 16 new admissions with a negative PCR test did not contract COVID-19. Outbreak management ended after 15 days without deaths from COVID-19. Conclusion: During the outbreak, PCR screening, the temporary stop in new admission until the availability of PCR results, and the risk-adapted cohorting of patients supplemented by consistent PCR tests of new admissions formed the basis for successful outbreak management. Treatment can be made possible despite high vulnerability. Close symptom monitoring and rapid implementation of measures reduce the risk. Repeated PCRs of direct-contact patients on day 3 can warrant pre-emptive antiviral therapy despite being asymptomatic; testing on day 5 makes it possible to shorten preventive isolation measures. The use of protective masks and self-monitoring by employees are fundamental to preventing further infections.

[Anticoagulation in older patients]. / Antikoagulation bei alten Patienten.

Prescribing oral anticoagulation in older patients for e.g. stroke prophylaxis has proven to be beneficial, but some special risks have to be considered. Renal function may be substantial impaired and dose reduction in at least some of the substances is recommended. Therefore, a closer monitoring of renal function is essential. Further as bleeding risk also increases with age usual scoring lists do less help this therapeutic dilemma than in younger patients. Adequate blood pressure control is essential in preventing intracerebral hemorrhage. Fall risk has to be assessed to initiate early compensation for this risk. Only high and unimprovable fall incidence may outweigh the benefits of oral anticoagulation therapy (>1 hospital admission per month due to a fall incident). Comprehensive geriatric assessment is crucial for early detection of specific adherence problems in older patients and is also helpful for discussion of individual deprescribing options in an end of live situation.

The Sex-Specific Impact of the FORTA (Fit-fOR-The-Aged) List on Medication Quality and Clinical Endpoints in Older Hospitalized Patients: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Little is known about the sex-specific impact of drug optimization tools such as the Fit fOR The Aged (FORTA) list on drug use and relevant clinical endpoints in older people. OBJECTIVE: We aimed to detect gender differences of interventional effects on medication quality and related clinical effects in the VALFORTA trial. PATIENTS AND METHODS: A sex-specific analysis of data from 409 patients (147 men and 262 women, mean age 79.4 and 82.7 years, respectively) in acute geriatric care comparing the control and FORTA intervention groups was performed. Changes of the FORTA score (sum of over- and undertreatment errors per patient), the incidence of adverse drug events (ADEs) during hospitalization, and several clinically relevant endpoints [e.g., the Barthel index (BI)] were tested for equivalence at a 20% margin. "Success" or "failure" for the development of these clinical endpoints was defined and their frequencies compared by a risk reduction analysis. RESULTS: Sex differences were insignificant for the reduction of the FORTA score, the improvement of BI, or over- and undertreatment errors (p > 0.05). In women only, the FORTA intervention significantly increased the number of patients without an ADE (p = 0.010). Statistical sex equivalence was found for the improvement of the FORTA scores, BI, and the number of prevented events (e.g., falls, confusion, or renal failure) (p < 0.05), but not for the improvement of specific mistreatments or over- and undertreatment scores under altered inclusion criteria (p > 0.05). CONCLUSIONS: Both sexes benefit equally from the FORTA intervention regarding the amelioration of the quality of drug treatment as well as several clinically relevant outcomes. In addition, the positive impact of the FORTA intervention on the number of adverse drug events appears to be greater in women. TRIAL REGISTRATION NUMBER: DRKS00000531.

A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.

BACKGROUND: Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. METHODS: A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. RESULTS: Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). CONCLUSION: This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.

[How to manage polypharmacia?] / Polypharmazie ­ Was tun?

Polypharmacia is a frequent challenge in modern medicine due to increasing complexity of both patients' aspects in an ageing society - multimorbidity - and progress of therapeutic approaches. Although risks are clearly increasing with number of simultaneously prescribed drugs, neither analysis of the polypharmacia-problem solely by number nor focusing on deprescribing strategies by number alone is sufficient. The optimum of an overall risk-benefit ratio in the multimorbidity situation has to be described and put into practice by an individualized approach. Pattern analysis may help this, by identifying both the most vulnerable patients and polypharmacia-pattern with pronounced risk burden. Patient vulnerability depends significantly on functional abilities and prioritizing therapeutic goals in a comprehensive deprescribing process needs to implement stage of life and disease.

Shared Decision-Making in Oncology: Preferences in Older versus Younger Patients of an Oncology Clinic - A Conjoint Analysis.

BACKGROUND: Data concerning older patients' preferences with regard to physician-patient interaction and the concept of shared decision-making (SDM) in oncology are still sparse although significantly influencing treatment planning. METHODS: Patients were recruited as a convenience sample from an outpatient oncology department. To test for patients' attitudes toward participating in clinical decisions, the PEF-FB-9 questionnaire (the German version of SDM-Q9) and the autonomy preference index (API) instrument were applied. A conjoint analysis was performed by a full set of vignettes exposing three different clinical attributes: clinical experience in oncology of the responsible physician, type of hospital, and type of physician-patient interaction in decision-making. Two independent cohorts were retrieved: patients aged <65 years and patients aged >70 years. RESULTS: A total of 71 patients were included. Younger subjects rated higher (44 vs. 10, p < 0.001) on the API scale. In both cohorts, physician-patient interaction received the highest preference values compared with type of hospital and physician experience. Analysis for age differences on preference values showed significantly higher values among the older patients concerning physician-patient interaction and lower values concerning type of hospital. Further analysis of the preferred type of physician-patient interaction revealed the highest preference in both cohorts for SDM. CONCLUSIONS: The high significance of physician-patient interaction could be proved. As a SDM approach is preferred in older and younger patients, an age-related different approach does not seem appropriate.

International Validation of the Turkish Inappropriate Medication Use in the Elderly (TIME) Criteria Set: A Delphi Panel Study.

OBJECTIVE: Explicit screening tools and implicit evaluation methods have been developed to assist healthcare professionals in the management of pharmacotherapy in older adults. As prescribing habits and locally available medications vary considerably between countries, guides tailored to the needs of specific regions may be required. We aimed to report the results of the international Delphi validation study for the Turkish Inappropriate Medication use in the Elderly (TIME) criteria set, which aims to detect inappropriate prescribing in older adults in Eastern Europe. METHODS: The study was conducted between June 2019 and March 2020. Delphi rounds were conducted by the TIME international working group, which included 11 internationally recognized experts in geriatric pharmacotherapy as Delphi panelists. They were asked to indicate to what extent they agreed or disagreed with each TIME criterion, taking into account both the available evidence and their own experience. We used a five-point Likert scale from 1 (strongly agree) to 5 (strongly disagree) and an online software program (SurveyMonkey®) to grade the level of agreement. Criteria with a median value of 1 or 2 and a 75th centile value of 1 or 2 were accepted, and criteria with a median value > 2 were rejected. Those with a median value of 1 or 2 but a 75th centile value > 2 were retained, to be assessed in the following round. The initial list of Delphi criteria comprised 153 TIME items. RESULTS: After three Delphi rounds, 134 criteria were accepted and seven criteria were rejected, while 12 criteria did not achieve consensus, and so were not included in the final validated set of TIME criteria. CONCLUSION: We developed the internationally validated TIME criteria set based on a Delphi process involving international experts. The validation study suggests that the TIME criteria set can be applied in both central and Eastern European settings. Further studies are needed to assess the utility and benefit of the TIME criteria in reducing inappropriate drug use and improving clinical outcomes.

Higher Fit-fOR-The-Aged (FORTA) Scores Comprising Medication Errors are Associated with Impaired Cognitive and Physical Function Tests in the VALFORTA Trial.

BACKGROUND: The Fit fOR The Aged (FORTA) list, a drug classification combining positive and negative labelling of drugs, has been clinically (VALFORTA-trial) validated to improve medication quality and clinical endpoints. OBJECTIVE: The objective of this study was to determine the association of medication quality with functional abilities tested in cognitive and physical function tests. PATIENTS AND METHODS: Data from the prospective, randomized controlled VALFORTA trial on 409 geriatric (mean age 81.53 years) in-hospital patients were tested for associations between the FORTA score (sum of over- and under-treatment errors) on admission and cognitive and physical function tests. Univariate and multivariate linear correlations corrected for age, sex, number of medications, number of chronic conditions, and body mass index as well as comparisons between high and low FORTA-score (cut-off 3) patients were performed. RESULTS: The FORTA score was significantly correlated with Instrumental Activities of Daily Living (p < 0.0001), the Tinetti test (p < 0.002), Essen Questionnaire on Age and Sleepiness (p < 0.0001), Mini-Mental State Examination (p < 0.0001), and handgrip strength (p < 0.04) in the univariate analysis, and with Instrumental Activities of Daily Living (p < 0.003), the Tinetti test (p < 0.003), and the Essen Questionnaire on Age and Sleepiness (p < 0.0001) in the multivariate analysis. Effect size was weak for Instrumental Activities of Daily Living (R-squared = 0.12) and the Tinetti test (R-squared = 0.03) and medium for the Essen Questionnaire on Age and Sleepiness (R-squared = 0.22). Significant differences between patients with high and low FORTA scores were found for Instrumental Activities of Daily Living, the Tinetti test, mini-nutritional assessments, Mini-Mental State Examination, Essen Questionnaire on Age and Sleepiness, and the Geriatric Depression Scale. All significant tests revealed that higher FORTA scores (lower medication quality) were associated with less favorable test outcomes. CONCLUSIONS: The FORTA score is associated with relevant aspects of comprehensive geriatric assessment, underlining the importance of medication quality for the functional and cognitive well-being of older patients. TRIAL REGISTRATION NUMBER: DRKS00000531.

Risk factors of worsening renal function in hospitalized elderly patients.

BACKGROUND: Worsening renal function during hospital treatment is a substantial hazard, especially for elderly hospitalized patients. However, data concerning the prevalence and significance of potential risk factors is lacking. METHODS: All patients admitted during a 6-month observation period to a department of general internal medicine and geriatrics were enrolled. Patients <65 yrs old were excluded. Data was assessed using a retrospective analysis of patient charts; 343/583 charts provided sufficient data for the analysis. Renal function was estimated by the Cockcroft and Gault formula. Worsening renal function was defined as a decline to <66.7% of the initial value. Laboratory values at admission (serum albumin, sodium and potassium), activities of daily living at admission (ADL-score), established medical diagnosis and medication prior to and during in-patient treatment were included in the analysis of potential risk factors. RESULTS: Renal function worsened in 6.1% of patients included. Risk factors were prescription of loop diuretics, trimethoprim/sulfamethoxazole or non-steroidal antiphlogistics during hospitalization. Hypernatremia, lower serum albumin and lower ADL-score at admission also demonstrated an association with a decline in renal function. However, an established diagnosis of heart failure, diabetes and hypertension were not predictive. CONCLUSION: Reduced physiological resources to maintain fluid and sodium balance are more predictive for worsening renal function than medical diagnosis alone. ADL-score and serum albumin could help further to identify patients at risk. Non-steroidal antiphlogistics are still frequently prescribed during in-patient treatment, although they are significant risk factors for renal function decline.

Bedside estimation of the glomerular filtration rate in hospitalized elderly patients.

AIMS: To evaluate the quality of bedside estimation of glomerular filtration rate (GFR) in hospitalized elderly patients. METHODS: We evaluated common estimators of GFR in 29 women and 32 men aged 60 and older hospitalized in a geriatric ward: creatinine clearance (CCR), the Cockcroft-Gault formula (CG), the modification of diet in renal disease formula (MDRD), Baracskay formula (BAR), and a newly developed formula derived recently by us (GCM). Inulin clearance (CINU) was used to assess GFR. Exclusion criteria were mental illness and urinary incontinence. RESULTS: According to Bland and Altman accuracy and precision of all estimators were low and there was an underestimation of actual GFR: CCR 38.9 ml/min; CG 39.7 ml/min; MDRD 19.8 ml/min; BAR 34.0 ml/min, and GCM: 24.7 ml/min. The accuracy and precision of all methods were even lower in patients with a GFR of >90 ml/min and in patients with diabetes. In receiver-operating characteristics (ROC analysis) all formulas were superior to serum creatinine and overall MDRD disclosed the best results in detecting both a GFR of <90 ml/min and <60 ml/min. CONCLUSIONS: In general, estimation errors are large in an acute care setting. However, formula estimation is clearly superior to serum creatinine and CCR. MDRD gave the best results but may be replaced by the more simple CG and GCM formulas, whereas BAR was inferior.

[An unusual cause of pulmonary fibrosis in a 71-year-old patient]. / Ungewöhnliche Ursache einer Lungenfibrose bei einer 71-jährigen Patientin.

CASE REPORT: A 71-year-old woman, suffering from spinal stenosis presented interstitial lung disease, albinism, and severe loss of visual acuity. On physical examination she showed tic-like automatism predominantly periorbital in the face and in the fingers. A computed tomography of the chest revealed typical findings of interstitial lung disease and additional mediastinal lymphomas and ground-glass attenuation in the lower regions of the lung. The findings of a transbronchial lung biopsy, presenting alveolar macrophages with ceroid-like material and platelet function studies proving slightly impaired platelet aggregation confirmed the clinical diagnosis of Hermansky-Pudlak syndrome. Sufficient pain control could be achieved without surgery and the patient was discharged home. 11 months after discharge, severe dyspnea and fever developed and finally the patient died of respiratory failure. CONCLUSION: The Hermansky-Pudlak syndrome is a rare cause of interstitial lung disease. In general, the lung disease presents in younger patients, but it may emerge in the elderly as well. Alveolar macrophages containing ceroid-like material are typical findings in BAL or lung biopsy. Furthermore impaired platelet aggregation and bleeding diathesis may be present. Both findings are useful to identify this rare disorder.

[Individualizing education for patients with diabetes attending an acute care unit]. / Individuelle Beratung von Patienten mit Diabetes mellitus im Akutkrankenhaus.

BACKGROUND: An increasing number of diagnostic procedures and shortened length of stay impede education for patients with diabetes mellitus attending an acute care unit. Therefore, an individualized approach to patient education may be more suitable. PATIENTS AND METHODS: The educational needs of inpatients with diabetes attending a department of general internal medicine were analyzed using a structured 5- to 10-minute interview. Within a period of 4 months, all patients with diabetes mellitus referred to the IVth Medical Department (speciality: geriatrics) were screened. Screening took place close to the day of admission. Following the screening interview, the interviewer initiated an individualized diabetes education according to the patient's needs and resources. The screening interview covered clinical data, functional limitations and disabilities, diabetes complications, patient's competence and motivation for further education. RESULTS: 205 patients with diabetes were seen (prevalence: 30.0%). 24 of them were newly diagnosed (prevalence: 3.5%). Overall, the screening revealed remarkable heterogeneity in patients with diabetes mellitus. 45 patients with previously known diabetes denied any diabetes education prior to hospital admission. Shorter diabetes duration, cognitive impairment, and treatment without insulin were significant and independent risk factors for missing diabetes education. Only 17.4% of patients on an insulin regimen prior to hospital admission performed no monitoring of blood glucose at home. Most patients holding their own blood glucose monitoring device performed daily measurements. Finally, 119 lessons of individual diabetes education were initialized in 73 patients (incidence: 17.4% of all admitted patients). CONCLUSION: Lack of education is common. As heterogeneity of patients with diabetes is striking, diabetes education has to be tailored to the individual needs and resources of the patients attending an acute care unit. Therefore, an individualized approach has proven to be suitable. In this context, a short structured interview is a useful tool for data assessment and scheduling of education lessons.