[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.

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.

Translatability scoring in prospective and retrospective COVID drug development cases.

BACKGROUND: The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 has led to an enormous surge of clinical research. So far, the speed and success rate of related drug development projects, especially of vaccines, is unprecedented. For the first time, this situation allowed for the opportunistic evaluation of a translatability score, originally proposed in 2009, in a prospective manner. METHODS: Several vaccines and treatments under development in clinical phase III trials were selected for translational scoring with the translatability score. Six prospective and six retrospective case studies were performed. The scores had to be determined for a fictive date before any results of the phase III trial were reported in any media. Spearman correlation analysis and a Kruskal Wallis test were performed for statistical evaluation. RESULTS: A significant correlation between the translatability scores and the clinical outcomes in translation was found, as judged on the basis of positive/intermediate/negative endpoint studies or market approval. The Spearman correlation analysis of all cases (r = 0.91, p < 0.001), the prospective cases alone (r = 0.93, p = 0.008), and the retrospective cases alone (r = 0.93, p = 0.008) showed a strong correlation between the score and outcome; R2 demonstrated a score-derived determination of outcomes by 86%. CONCLUSIONS: The score detects strengths and weaknesses of a given project, resulting in the opportunity of selective amelioration of a project, as well as prospective portfolio risk balancing. Its substantial predictive value that has been demonstrated here for the first time could be of particular interest for biomedical industry (pharmaceutical and device manufacturers), funding agencies, venture capitalists, and researchers in the area. Future evaluations will have to address the generalizability of results obtained in an exceptional pandemic situation, and the potential adaptations of weighing factors/items to particular therapeutic areas.

Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician.

INTRODUCTION: Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. METHODS: A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. DISCUSSION: The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. TRIAL REGISTRATION: German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.

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.

Many or too many progesterone membrane receptors? Clinical implications.

Several receptors for nongenomically initiated actions of progesterone (P4) exist, namely membrane-associated P4 receptors (MAPRs), membrane progestin receptors (mPRs), receptors for neurosteroids [GABAA receptor (GABAAR), NMDA receptor, sigma-1 and -2 receptors (S1R/S2R)], the classical genomic P4 receptor (PGR), and α/ß hydrolase domain-containing protein 2 (ABHD2). Two drugs related to this field have been approved: brexanolone (Zulresso™) for the treatment of postpartum depression, and ganaxolone (Ztalmy™) for the treatment of CDKL5 deficiency disorder. Both are derivatives of P4 and target the GABAAR. Several other indications are in clinical testing. CT1812 (Elayta™) is also being tested for the treatment of Alzheimer's disease (AD) in Phase 2 clinical trials, targeting the P4 receptor membrane component 1 (PGRMC1)/S2R complex. In this Review, we highlight emerging knowledge on the mechanisms of nongenomically initiated actions of P4 and its derivatives.

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.

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.

Automated Charting of the Visual Space of Housefly Compound Eyes.

This paper describes the automatic measurement of the spatial organization of the visual axes of insect compound eyes, which consist of several thousands of visual units called ommatidia. Each ommatidium samples the optical information from a small solid angle, with an approximate Gaussian-distributed sensitivity (half-width on the order of 1˚) centered around a visual axis. Together, the ommatidia gather the visual information from a nearly panoramic field of view. The spatial distribution of the visual axes thus determines the eye's spatial resolution. Knowledge of the optical organization of a compound eye and its visual acuity is crucial for quantitative studies of neural processing of the visual information. Here we present an automated procedure for mapping a compound eye's visual axes, using an intrinsic, in vivo optical phenomenon, the pseudopupil, and the pupil mechanism of the photoreceptor cells. We outline the optomechanical setup for scanning insect eyes and use experimental results obtained from a housefly, Musca domestica, to illustrate the steps in the measurement procedure.

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.