Higher FORTA (Fit fOR The Aged) scores are associated with poor functional outcomes, dementia, and mortality in older people.

PURPOSE: Higher Fit fOR The Aged (FORTA) scores have been shown to be negatively associated with adverse clinical outcomes in older hospitalized patients. This has not been evaluated in other health care settings. The aim of this study was to examine the association of the FORTA score with relevant outcomes in the prospective AgeCoDe-AgeQualiDe cohort of community-dwelling older people. In particular, the longitudinal relation between the FORTA score and mortality and the incidence of dementia was evaluated. METHODS: Univariate and multivariate correlations between the FORTA score and activities of daily living (ADL) or instrumental activities of daily living (IADL) as well as comparisons between high vs. low FORTA scores were conducted. RESULTS: The FORTA score was significantly correlated with ADL/IADL at baseline and at all follow-up visits (p < 0.0001). ADL/IADL results of participants with a low FORTA score were significantly better than in those with high FORTA scores (p < 0.0001). The FORTA score was also significantly (p < 0.0001) correlated with ADL/IADL in the multivariate analysis. Moreover, the mean FORTA scores of participants with dementia were significantly higher (p < 0.0001) than in those without dementia at follow-up visits 6 through 9. The mean FORTA scores of participants who died were significantly higher than those of survivors at follow-up visits 7 (p < 0.05), 8 (p < 0.001), and 9 (p < 0.001). CONCLUSION: In this study, an association between higher FORTA scores and ADL as well as IADL was demonstrated in community-dwelling older adults. Besides, higher FORTA scores appear to be linked to a higher incidence of dementia and even mortality.

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.

A systematic review and novel classification of listing tools to improve medication in older people.

PURPOSE: Suboptimal drugs therapy is a threat to older people, and listing tools providing guidance are developed to address this problem. METHODS: A systematic review was performed to identify and analyze such tools published until February 2018. A novel categorization was developed to separate patient-in-focus listing approaches (PILA) providing disease-related positive and negative guidance from drug-oriented, mostly negative listing approaches (DOLA, DOLA+: with disease specification). RESULTS: In total, 76 tools were identified; only 9 were classified as PILA, 26 as DOLA, and 38 as DOLA+. Three DOLA(+) only address dementia. Most tools were developed in Europe or the USA and address community-dwellers. Thirty-two utilized a Delphi process, and only 10 provide a scoring system. Twenty tools utilize a questionnaire but no structured guidance or answers. Importantly, only 12 interventional clinical trials were identified reporting not only medication quality measures, but also clinical endpoints (e.g. falls, adverse drug reactions, hospitalization). For PILA, 4 trials showed positive, one negative clinical effects of a controlled intervention, for DOLA(+) 1 was positive, 7 negative (Fisher's exact test p < 0.05). DISCUSSION: An abundance of listing tools has been created. DOLAs that may be applied without intricate patient knowledge prevail over PILAs by sevenfold; unfortunately their clinical validation seems to be far less successful than that of patient-initiated approaches. CONCLUSION: Drug therapy in older people has to be tailored to their individual, very divergent needs; tools requiring detailed medical knowledge about the patient as the starting point for medication optimization provide the best support.

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).

[The FORTA (Fit fOR The Aged) List]. / Die FORTA (Fit fOR The Aged) Liste.

BACKGROUND: Multimorbidity and the resulting polypharmacy are widespread in the very old and the evidence on the efficacy and safety of drugs in older people is sparse. Driven by guidelines, this often leads to inappropriate prescribing and drug-related problems. MATERIAL AND METHODS: To improve this, numerous listing approaches were developed as tools to optimize medication. These approaches can be divided into drug-oriented listing approaches (DOLA), such as the Beers Criteria®, a list of potentially inappropriate medications for older people or patient-in-focus listing approaches (PILA), such as the Fit fOR The Aged (FORTA) list. RESULTS: The most recent version of the FORTA list was published in 2022 and contains 299 drugs or drug groups targeting 30 age-related indications. In addition, several country-specific or region-specific FORTA lists, such as the EURO-FORTA list have been developed. Very few randomized controlled trials have demonstrated the utility of existing listing approaches for improving clinical outcomes, such as adverse drug events, falls or hospitalizations. In the VALFORTA study, the use of FORTA led to a significant improvement in medication treatment. In addition, important clinical endpoints, such as the occurrence of adverse drug events (number needed to treat = 5), activities of daily living (ADL) and the incidence of falls were significantly improved by the FORTA intervention in a clinically relevant manner. CONCLUSION: Based on these promising results, the use of the FORTA list for medication optimization in older patients is recommended; the prerequisite for application is the needs analysis for drugs according to diagnoses, severity, life expectancy, functional status, and patient wishes.

Validation of MyFORTA: An Automated Tool to Improve Medications in Older People Based on the FORTA List.

BACKGROUND: Listing tools have been developed to improve medications in older patients, including the Fit fOR The Aged (FORTA) list, a clinically validated, positive-negative list of medication appropriateness. Here, we aim to validate MyFORTA, an automated tool for individualized application of the FORTA list. METHODS: 331 participants of a multi-center cohort study (AgeCoDe) for whom the FORTA score (sum of overtreatment and undertreatment errors) had been determined manually (gold standard [GS]) were reassessed using the automated MyFORTA (MF) tool. This tool determines the score from ATC and ICD codes combined with clinical parameters. RESULTS: The FORTA scores were 9.01 ± 2.91 (mean ± SD, MF) versus 6.02 ± 2.52 (GS) (p < 0.00001). Removing undertreatment errors for calcium/vitamin D (controversial guidelines) and influenza/pneumococcal vaccinations (no robust information in the database), the difference decreased: 7.5 ± 2.7 (MF) versus 5.98 ± 2.55 (GS) (p < 0.00001). The remaining difference was driven by, for example, missing nitro spray in coronary heart disease/acute coronary syndrome as the related information was rarely found in the database, but notoriously detected by MF. Three hundred and forty errors from those 100 patients with the largest score deviation accounted for 68% of excess errors by MF. CONCLUSION: MF was more sensitive to detect medication errors than GS, all frequent errors only detected by MF were plausible, and almost no adaptations of the MF algorithm seem indicated. This automated tool to check medication appropriateness according to the FORTA list is now validated and represents the first clinically directed algorithm in this context. It should ease the application of FORTA and help to implement the proven beneficial effects of FORTA on clinical endpoints.

The EURO-FORTA (Fit fOR The Aged) List Version 2: Consensus Validation of a Clinical Tool for Improved Pharmacotherapy in Older Adults.

BACKGROUND: The aging of our societies leads to a higher prevalence of multimorbidity and therefore polypharmacy, which often results in inappropriate drug treatment. To address this issue, numerous listing approaches, such as the Fit fOR The Aged (FORTA) list have been developed. FORTA's positive impact on the quality of medications and relevant clinical outcomes has been shown. Based on new emerging evidence and experiences with the existing FORTA lists, we aimed to update the FORTA lists in several European countries/regions. METHODS: Two-step Delphi consensus procedures were conducted in Poland, UK/Ireland, Italy, Spain, the Nordic countries, The Netherlands and France. The existing European FORTA lists served as survey proposals. RESULTS: Thirty-two experts agreed to take part in this study (return rate: 96.9%). The country/region-specific overall consensus for all items and participants after the first round was > 90%. FORTA lists from six participating countries, plus the FORTA list for the German-speaking countries, were collated into the new EURO-FORTA List, which now contains 267 items aligned to 27 indications. Three items were added to the EURO-FORTA List, and no drugs were deleted. Eight FORTA items were relabeled, and 96.9% of the labels remained unchanged. CONCLUSION: In this study, seven new country/region specific FORTA lists, as well as a new overarching EURO-FORTA List, were developed. An overall increase in the mean consensus coefficient and increases for all disease-specific mean consensus coefficients show a wider consensus among participants. The new lists have the potential to improve drug therapy in older people internationally.

Medication optimization according to the Fit fOR The Aged (FORTA) rules improves functional status in patients hospitalized for geriatric rehabilitation.

INTRODUCTION: Functional status is one of the most important issues of geriatric care. Polypharmacy seems to be a modifiable factor associated with functional decline in older adults. However, the impact of pharmacotherapy optimization on the activities of daily living in patients undergoing geriatric rehabilitation has not been investigated prospectively so far. METHODS: This post hoc analysis of a subsample of the VALFORTA study included individuals only undergoing geriatric rehabilitation with a length of in-hospital stay of at least 14 days. Medication was modified according to the FORTA rules in the intervention group while in the control group standard drug treatment was applied. Both groups received comprehensive geriatric treatment. RESULTS: The intervention and control groups consisted of 96 and 93 individuals respectively. They did not differ according to basic data except for age and Charlson Comorbidity Index (CCI) on admission. On discharge, activities of daily living (Barthel index, BI) were improved in both groups. An increase of at least 20 points of the BI was observed in 40% of patients in the intervention group and in 12% of patients in the control group (p< 0.001). Logistic regression analysis with an increase of at least 20 BI-points was significantly and independently associated with patient group (2.358, p< 0.02), BI on admission (0.957, p< 0.001), and the CCI (0.793, p< 0.041). CONCLUSION: This post hoc analysis of a subsample of older individuals hospitalized for geriatric rehabilitation demonstrates a significant additional improvement in activities of daily living by modification of medication according to FORTA. REGISTRATION: DRKS-ID: DRKS00000531.

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.

Deprescribing practices, habits and attitudes of geriatricians and geriatricians-in-training across Europe: a large web-based survey.

PURPOSE: To provide an overview of the current deprescribing attitudes, practices, and approaches of geriatricians and geriatricians-in-training across Europe. METHODS: An online survey was disseminated among European geriatricians and geriatricians-in-training. The survey comprised Likert scale and multiple-choice questions on deprescribing approaches and practices, deprescribing education and knowledge, and facilitators/barriers of deprescribing. Responses to the survey questions and participant characteristics were quantified and differences evaluated between geriatricians and geriatricians-in-training and between European regions. RESULTS: The 964 respondents (median age 42 years old; 64% female; 21% geriatricians-in-training) were generally willing to deprescribe (98%) and felt confident about deprescribing (85%). Despite differences across European regions, the most commonly reported reasons for deprescribing were functional impairment and occurrence of adverse drug reactions. The most important barriers for deprescribing were patients' unwillingness, fear of negative consequences, lack of time, and poor communication between multiple prescribers. Perceived risk of adverse drug reactions was highest for psychotropic drugs, nonsteroidal anti-inflammatory drugs, cardiovascular drugs, and opioid analgesics. Only one in four respondents (23% of geriatricians and 37% of geriatricians-in-training) think education in medical school had sufficiently prepared them for deprescribing in clinical practice. They reported that their future deprescribing activities would probably increase with improved information sharing between various prescribers, deprescribing recommendations in guidelines, and increased education and training. Approximately 90% think that a paradigm shift is required for prescribers and patients, increasing focus on the possible benefits of deprescribing (potentially) inappropriate medications. CONCLUSIONS: Based on the outcomes of this survey, we recommend investing in improved inter-professional communication, better education and evidence-based recommendations to improve future patient-centered deprescribing practices.

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.

Polypharmacy in older adults: a narrative review of definitions, epidemiology and consequences.

BACKGROUND: The number of older adults has been constantly growing around the globe. Consequently, multimorbidity and related polypharmacy have become an increasing problem. In the absence of an accepted agreement on the definition of polypharmacy, data on its prevalence in various studies are not easily comparable. Besides, the evidence on the potential adverse clinical outcomes related to polypharmacy is limited though polypharmacy has been linked to numerous adverse clinical outcomes. This narrative review aims to find and summarize recent publications on definitions, epidemiology and clinical consequences of polypharmacy. METHODS: The MEDLINE database was used to identify recent publications on the definition, prevalence and clinical consequences of polypharmacy using their respective common terms and their variations. Systematic reviews and original studies published between 2015 and 2020 were included. RESULTS: One hundred and forty-three definitions of polypharmacy and associated terms were found. Most of them are numerical definitions. Its prevalence ranges from 4% among community-dwelling older people to over 96.5% in hospitalized patients. In addition, numerous adverse clinical outcomes were associated with polypharmacy. CONCLUSION: The term polypharmacy is imprecise, and its definition is yet subject to an ongoing debate. The clinically oriented definitions of polypharmacy found in this review such as appropriate or necessary polypharmacy are more useful and relevant. Regardless of the definition, polypharmacy is highly prevalent in older adults, particularly in nursing home residents and hospitalized patients. Approaches to increase the appropriateness of polypharmacy can improve clinical outcomes in older adults.

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.

The JAPAN-FORTA (Fit fOR The Aged) list: Consensus validation of a clinical tool to improve drug therapy in older adults.

PURPOSE: Multimorbidity and subsequent polypharmacy are highly prevalent in older people. To improve inappropriate drug treatment, listing approaches such as the Beers or FORTA lists have been developed. Latter is the only clinically validated drug list issuing both positive (FORTA labels A, B) and negative (FORTA labels C, D) recommendations. Several country-specific FORTA lists have been developed to acknowledge national prescription habits, drug availabilities, and expert opinions. Here, this approach was applied to Japan. METHODS: 13 Japanese experts in geriatric pharmacotherapy participated as raters in a 2-step Delphi consensus validation of the FORTA list. The proposal of FORTA labels was based on the EURO-FORTA List and raters were asked to add, delete or re-evaluate medications, add relevant diagnoses and comments. RESULTS: The final JAPAN-FORTA list contains 210 items aligned to 24 main indication groups. 15 items were added to the proposal and the 71 items either not used/approved in Japan or not evaluated by any rater (oncological drugs) were removed. Excluding latter, the JAPAN-FORTA list differs from the EURO-FORTA list by 23 %. Removals mainly concerned psychotropic drugs. A maximum of one label was changed per indication. The majority (96.9 percent) of the proposed FORTA labels were confirmed, only 6 labels had to be changed. CONCLUSION: The new JAPAN-FORTA list addresses the appropriateness of drug treatment in older people in Japan. This unique listing approach issuing both positive and negative medication recommendations has been shown to improve of drug therapy in older adults and its country-specific version is now available for Japan.

The U.S.-FORTA (Fit fOR The Aged) List: Consensus Validation of a Clinical Tool to Improve Drug Therapy in Older Adults.

BACKGROUND/OBJECTIVES: Polypharmacy and multimorbidity is a threat to older people; hence, listing approaches should support physicians to optimize medication. The FORTA (Fit fOR The Aged) classification of drug appropriateness for older people provides positive or negative labels: A (A-bsolutely), B (B-eneficial), C (C-areful), and D (D-on't). Based on these categories, FORTA-labeled drug lists were developed in 7 European countries or regions; the same approach was used to develop a U.S.-FORTA List reflecting the country-specific availability and usage of drugs. DESIGN/SETTING: A 2-step Delphi-type approach was employed to add, remove, or relabel drugs from the listing proposal and to add or remove new indications. The proposal utilized the European (EURO)-FORTA list as template. PARTICIPANTS: Eight US-based geriatricians/pharmacists served as raters. MEASUREMENTS: Raters gave recommendations and comments on the list items. RESULTS: The first U.S.-FORTA List contains 273 items aligned to 27 main indication groups; 30 drugs and drug groups were added, and 23 removed as being unavailable in the United States. The highest percentage of changes in FORTA labels as compared to the EURO-FORTA List occurred for sleep disorders associated with dementia (40%). In 8 indications, the labels for 11 items were different from the proposal. Thus, for the majority of the items (n = 232, 95.5%), the proposals were accepted by the US raters. Only 16 (6.6%) of the proposed items (n = 243) had to be re-evaluated in the second round as a result of inconsistent rating in the first round. CONCLUSIONS AND IMPLICATIONS: The U.S.-FORTA List addresses the appropriateness of drugs for older people in the United States reflecting country-specific availability, usage, and expert rating. As shown for the FORTA list in Europe, this listing approach is among the few that are clinically validated and improve well-being and geriatric outcomes. The U.S.-FORTA List now largely enhances the global availability of this approach.

A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019).

INTRODUCTION: Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. METHODS: A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. RESULTS: A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. CONCLUSION: OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.

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.

Association of polypharmacy and hyperpolypharmacy with frailty states: a systematic review and meta-analysis.

PURPOSE: To investigate: (1) the cross-sectional association between polypharmacy, hyperpolypharmacy and presence of prefrailty or frailty; (2) the risk of incident prefrailty or frailty in persons with polypharmacy, and vice versa. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/1998 to 5/2/2018. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I2 statistic and publication bias with Egger's and Begg's tests. RESULTS: Thirty-seven studies were included. The pooled proportion of polypharmacy in persons with prefrailty and frailty was 47% (95% CI 33-61) and 59% (95% CI 42-76), respectively. Increased odds ratio of polypharmacy were seen for prefrail (pooled OR = 1.52; 95% CI 1.32-1.79) and frail persons (pooled OR = 2.62, 95% CI 1.81-3.79). Hyperpolypharmacy was also increased in prefrail (OR = 1.95; 95% CI 1.41-2.70) and frail (OR = 6.57; 95% CI 9.57-10.48) persons compared to robust persons. Only seven longitudinal studies reported data on the risk of either incident prefrailty or frailty in persons with baseline polypharmacy. A significant higher odds of developing prefrailty was found in robust persons with polypharmacy (pooled OR = 1.30; 95% CI 1.12-1.51). We found no papers investigating polypharmacy incidence in persons with prefrailty/frailty. CONCLUSIONS: Polypharmacy is common in prefrail and frail persons, and these individuals are also more likely to be on extreme drug regimens, i.e. hyperpolypharmacy, than robust older persons. More research is needed to investigate the causal relationship between polypharmacy and frailty syndromes, thereby identifying ways to jointly reduce drug burden and prefrailty/frailty in these individuals. PROSPERO REGISTRATION NUMBER: CRD42018104756.