Project description:BackgroundThe 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.MethodsTwo-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.ResultsThirty-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.ConclusionIn 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.
Project description:BackgroundMultimorbidity and polypharmacy represent a major problem for elderly patients; improvement of medication schemes is important and listing approaches (e.g. Beers list) are considered to be potentially useful.ObjectivesThe aim of this study was to perform expert consensus validation of the FORTA (Fit fOR The Aged) List, a drug classification combining positive and negative labelling of drugs chronically prescribed to elderly patients.MethodsA two-round Delphi procedure was conducted involving 20 experts, 17 geriatric internists and 3 geriatric psychiatrists from Germany and Austria, evaluating the labels assigned to 190 substances or substance groups. These labels ranged from A (indispensable), B (beneficial), C (questionable) to D (avoid), depending on the state of evidence for safety, efficacy and overall age-appropriateness. The experts were also requested to suggest additional substances and indication areas for assessment and possible inclusion in the FORTA List. A weighted (corrected) consensus coefficient was generated for each substance to reflect (1) agreement with the original label, and (2) distribution among raters' labels.ResultsThe overall consensus for all items and raters was 92% (corrected). For 54/190 items (28.4%), a unanimous response was achieved as to the original author-based FORTA label choice. Twenty-four substances (12.6%) fell short of the consensus cutoff and were re-evaluated in a second round. This yielded confirmation of 171/190, or 90%, of the original author-based FORTA labels. A total of 35 new substances were also accepted for the FORTA List. Drugs used for dementia and dementia syndromes provoked particular response heterogeneity.ConclusionThe FORTA List now reflects a wider consensus among experts, increasing its validity for clinical use. It represents a tool to improve the quality of drug prescription in older patients by identifying both inappropriate and omitted drugs, and thus overtreatment and undertreatment. The validation of FORTA's impact on clinical endpoints has yielded promising preliminary results, to be corroborated in ongoing larger trials.
Project description:Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the prevalence and characteristics of PIM prescriptions on the gerontopsychiatric ward of a university hospital in Germany. To this aim, medication charts of 92 patients (mean age 75.9 ± 7.7 years; 66.3% female) were analyzed on a weekly basis until patient discharge by utilization of the PRISCUS list and the FORTA classification. Overall, 335 medication reviews comprising 2363 drug prescriptions were analyzed. 3.0% of the prescribed drugs were PIMs according to the PRISCUS list, with benzodiazepines and Z-drugs accounting for nearly half (49.3%) of all PIM prescriptions. 30.4% of the patients were prescribed at least one PRISCUS-PIM, while 43.5% of the study population took at least one FORTA class D drug. A considerable proportion of gerontopsychiatric patients were affected by PIMs; however, the overall number of PIM prescriptions in the study population was low. Further improvements in the quality of prescribing should target the use of sedating agents such as benzodiazepines and Z-drugs. Physicians should be aware of discrepancies between the PRISCUS list and the FORTA classification.
Project description:BackgroundLittle 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.ObjectiveWe aimed to detect gender differences of interventional effects on medication quality and related clinical effects in the VALFORTA trial.Patients and methodsA 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.ResultsSex 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).ConclusionsBoth 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 numberDRKS00000531.
Project description:PurposeHigher 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.MethodsUnivariate 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.ResultsThe 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).ConclusionIn 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.
Project description:Children with Langerhnans cell histiocytosis (LCH) develop granulomatous lesions with characteristic clonal CD207+ dendritic cells that can arise as single lesions or life-threatening disseminated disease. Despite the wide range of clinical presentations, LCH lesions are histologically indistinguishable based on severity of disease, and uncertain classification as an immune versus neoplastic disorder has historically challenged the development of optimal clinical strategies for patients with LCH. Recently, activating somatic mutations in MAPK pathway genes, most notably BRAFV600E, have been discovered in almost all cases of LCH. Further, the stage of myeloid differentiation in which the mutation arises defines the extent of disease and risk of developing LCH-associated neurodegeneration. MAPK activation in LCH precursor cells drives myeloid differentiation, inhibits migration, and inhibits apoptosis, resulting in accumulation of resilient pathologic dendritic cells that recruit and activate T cells. Recurrent somatic mutations in MAPK pathway genes have also been identified in related histiocytic disorders: juvenile xanthogranuloma, Erdheim-Chester disease, and Rosai-Dorfman disease. New insights into pathogenesis support reclassification of these conditions as a myeloid neoplastic disorders. Continued research will uncover opportunities to identify novel targets and inform personalized therapeutic strategies based on cell of origin, somatic mutation, inherited risk factors, and residual disease.
Project description:CLUB ("Candidate List of yoUr Biomarkers") is a freely available, web-based resource designed to support Cancer biomarker research. It is targeted to provide a comprehensive list of candidate biomarkers for various cancers that have been reported by the research community. CLUB provides tools for comparison of marker candidates from different experimental platforms, with the ability to filter, search, query and explore, molecular interaction networks associated with cancer biomarkers from the published literature and from data uploaded by the community. This complex and ambitious project is implemented in phases. As a first step, we have compiled from the literature an initial set of differentially expressed human candidate cancer biomarkers. Each candidate is annotated with information from publicly available databases such as Gene Ontology, Swiss-Prot database, National Center for Biotechnology Information's reference sequences, Biomolecular Interaction Network Database and IntAct interaction. The user has the option to maintain private lists of biomarker candidates or share and export these for use by the community. Furthermore, users may customize and combine commonly used sets of selection procedures and apply them as a stored workflow using selected candidate lists. To enable an assessment by the user before taking a candidate biomarker to the experimental validation stage, the platform contains the functionality to identify pathways associated with cancer risk, staging, prognosis, outcome in cancer and other clinically associated phenotypes. The system is available at http://club.bii.a-star.edu.sg.
Project description:Rationale, aims and objectivesThe field of implementation science is critical for embedding research evidence into healthcare practice, benefiting individuals, organizations, governments, and the broader community. Implementation science is messy and complex, underpinned by many theories and frameworks. Efficacious interventions for older people with multiple comorbidities exist, yet many lack effectiveness evaluation relevant to pragmatic implementation within aged care practice. This article outlines the conceptualization and development of an Implementation Framework for Aged Care (IFAC), fit-for-purpose for an aged care organization, Bolton Clarke, intent on embedding evidence into practice.MethodA four-stage process was adopted to (1) explore context and relevant literature to conceptualize the IFAC; (2) identify key elements for a draft IFAC; (3) expand elements and refine the draft in consultation with experts and (4) apply the IFAC to three existing projects, identifying key learnings. A checklist to operationalize the IFAC was then developed.ResultsThe IFAC is grounded in codesign principles and encapsulated by the implementation context, from a social, cultural and political perspective. The IFAC addresses the questions of (1) why do we need to change?; (2) what do we know?; (3) who will benefit?; (4) who will make the change?; (5) what strategies will be used?; and (6) what difference are we making? Three pilot projects: early adoption of a Wellness and Reablement approach; a care worker and virtual physiotherapist-led program to prevent falls; and a therapeutic horticulture program for residential communities, highlight learnings of applying the IFAC in practice.ConclusionThis fit-for-purpose IFAC was developed for a proactive and responsive aged care provider. The simplicity of the six-question IFAC is underpinned by substantial theoretical perspectives for its elements and their connections. This complexity is then consolidated into an 18-question checklist to operationalize the IFAC, necessary to advance the translation of evidence into clinical practice.
Project description:There is growing demand for digital intelligence testing. In the current study, we evaluated the validity of an online version of the revised German Culture Fair Intelligence Test (CFT 20-R). A total of 4100 children from the third and fourth grades completed the online version using a smartphone or tablet. Subsequently, 220 of these children also completed the paper-pencil (PP) version. The internal consistency and construct validity of the online version appeared to be acceptable. The correlation between the raw scores and school grades in German and mathematics was slightly lower than expected. On average, the raw scores for the PP version were revealed to be higher, which was probably due to a learning effect. At the item level, the results show small differences for the subtests Series and Matrices, possibly caused by small differences in the presentation of the items. The correspondence between the versions did not depend on children's levels of impulsivity or intelligence. Altogether, the results support the hypothesis that the online version of the CFT 20-R is a valid measure of general fluid intelligence and highlight the need for separate norms.