EULAR recommendations for the involvement of patient research partners in rheumatology research: 2023 update.

BACKGROUND: Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary. METHODS: In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale). RESULTS: The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96. CONCLUSION: The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research.

Assessment of the Quality and Readability of Information Provided by ChatGPT in Relation to the Use of Platelet-Rich Plasma Therapy for Osteoarthritis.

Objective: This study aimed to evaluate the quality and readability of information generated by ChatGPT versions 3.5 and 4 concerning platelet-rich plasma (PRP) therapy in the management of knee osteoarthritis (OA), exploring whether large language models (LLMs) could play a significant role in patient education. Design: A total of 23 common patient queries regarding the role of PRP therapy in knee OA management were presented to ChatGPT versions 3.5 and 4. The quality of the responses was assessed using the DISCERN criteria, and readability was evaluated using six established assessment tools. Results: Both ChatGPT versions 3.5 and 4 produced moderate quality information. The quality of information provided by ChatGPT version 4 was significantly better than version 3.5, with mean DISCERN scores of 48.74 and 44.59, respectively. Both models scored highly with respect to response relevance and had a consistent emphasis on the importance of shared decision making. However, both versions produced content significantly above the recommended 8th grade reading level for patient education materials (PEMs), with mean reading grade levels (RGLs) of 17.18 for ChatGPT version 3.5 and 16.36 for ChatGPT version 4, indicating a potential barrier to their utility in patient education. Conclusions: While ChatGPT versions 3.5 and 4 both demonstrated the capability to generate information of moderate quality regarding the role of PRP therapy for knee OA, the readability of the content remains a significant barrier to widespread usage, exceeding the recommended reading levels for PEMs. Although ChatGPT version 4 showed improvements in quality and source citation, future iterations must focus on producing more accessible content to serve as a viable resource in patient education. Collaboration between healthcare providers, patient organizations, and AI developers is crucial to ensure the generation of high quality, peer reviewed, and easily understandable information that supports informed healthcare decisions.

Patient outcomes in longitudinal observational studies (POLOS) of rheumatoid arthritis: Determining the OMERACT core domain set.

OBJECTIVE: To define and select rheumatoid arthritis (RA)-specific core domain set for Longitudinal Observational Studies (LOS) within the Outcome Measures in Rheumatology (OMERACT) framework. METHODS: A three-round online Delphi exercise, including patient research partners (PRPs) and other community partners in healthcare, was conducted. Domains scored 7-9 (i.e., critically important to include) by ≥ 70 % of participants in both groups were included. Items were consolidated in a subsequent dedicated meeting. RESULTS: Nineteen domains scored ≥ 70 % consensus in both groups. The focus group refined these into a list of twelve domains. CONCLUSION: The achieved consensus will inform the next steps of developing the core domain set for LOS in RA.

2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.

Trained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme.

Trained immunity defines long-lasting adaptations of innate immunity based on transcriptional and epigenetic modifications of myeloid cells and their bone marrow progenitors [M. Divangahi et al., Nat. Immunol. 22, 2-6 (2021)]. Innate immune cells, however, do not exclusively differentiate between foreign and self but also react to host-derived molecules referred to as alarmins. Extracellular "labile" heme, released during infections, is a bona fide alarmin promoting myeloid cell activation [M. P. Soares, M. T. Bozza, Curr. Opin. Immunol. 38, 94-100 (2016)]. Here, we report that labile heme is a previously unrecognized inducer of trained immunity that confers long-term regulation of lineage specification of hematopoietic stem cells and progenitor cells. In contrast to previous reports on trained immunity, essentially mediated by pathogen-associated molecular patterns, heme training depends on spleen tyrosine kinase signal transduction pathway acting upstream of c-Jun N-terminal kinases. Heme training promotes resistance to sepsis, is associated with the expansion of self-renewing hematopoetic stem cells primed toward myelopoiesis and to the occurrence of a specific myeloid cell population. This is potentially evoked by sustained activity of Nfix, Runx1, and Nfe2l2 and dissociation of the transcriptional repressor Bach2. Previously reported trained immunity inducers are, however, infrequently present in the host, whereas heme abundantly occurs during noninfectious and infectious disease. This difference might explain the vanishing protection exerted by heme training in sepsis over time with sustained long-term myeloid adaptations. Hence, we propose that trained immunity is an integral component of innate immunity with distinct functional differences on infectious disease outcome depending on its induction by pathogenic or endogenous molecules.

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.

2020 EULAR points to consider for the prevention, screening, assessment and management of non-adherence to treatment in people with rheumatic and musculoskeletal diseases for use in clinical practice.

BACKGROUND: Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. OBJECTIVES: The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. METHODS: An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients' needs. The level of agreement ranged from 9.5 to 9.9 out of 10. CONCLUSIONS: These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.

Prevention, screening, assessing and managing of non-adherent behaviour in people with rheumatic and musculoskeletal diseases: systematic reviews informing the 2020 EULAR points to consider.

OBJECTIVE: To analyse how non-adherence to prescribed treatments might be prevented, screened, assessed and managed in people with rheumatic and musculoskeletal diseases (RMDs). METHODS: An overview of systematic reviews (SR) was performed in four bibliographic databases. Research questions focused on: (1) effective interventions or strategies, (2) associated factors, (3) impact of shared decision making and effective communication, (4) practical things to prevent non-adherence, (5) effect of non-adherence on outcome, (6) screening and assessment tools and (7) responsible healthcare providers. The methodological quality of the reviews was assessed using AMSTAR-2. The qualitative synthesis focused on results and on the level of evidence attained from the studies included in the reviews. RESULTS: After reviewing 9908 titles, the overview included 38 SR on medication, 29 on non-pharmacological interventions and 28 on assessment. Content and quality of the included SR was very heterogeneous. The number of factors that may influence adherence exceed 700. Among 53 intervention studies, 54.7% showed a small statistically significant effect on adherence, and all three multicomponent interventions, including different modes of patient education and delivered by a variety of healthcare providers, showed a positive result in adherence to medication. No single assessment provided a comprehensive measure of adherence to either medication or exercise. CONCLUSIONS: The results underscore the complexity of non-adherence, its changing pattern and dependence on multi-level factors, the need to involve all stakeholders in all steps, the absence of a gold standard for screening and the requirement of multi-component interventions to manage it.

Development and Formative Evaluation of a Communication Skills Training Program for Persons with Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: Our aim was to develop and evaluate a two-module training program (KOKOS-Rheuma) specifically designed to enhance the ability of persons with rheumatic and musculoskeletal diseases to communicate in various everyday situations. DESIGN: KOKOS-Rheuma deals with communication at work (particularly superiors), with physicians, acquaintances, strangers and staff members of authorities and institutions and focuses on communication skills such as "saying no" and "giving and receiving feedback." Members of the German League against Rheumatism (GLR) were trained to deliver the program to self-help groups over two sessions or in a full-day session. The participants, trainers and observers completed a short evaluation form after each module or at the end of the full-day session. MAIN OUTCOME MEASURES: The evaluation was based on 232 participant, 51 trainer, and 8 observer evaluation forms. RESULTS: The participants rated all aspects of the training as good. The training was rated higher in the single session format. The great majority would recommend the course to other people. CONCLUSION: After the revision of the training manual, KOKOS-Rheuma can be recommended for inclusion in the training schedule of the GLR. We recommend that future trainers receive more extensive preparation for delivering the course that highlights the preparation time required.

Spontaneous Growth and Effect of Early Therapy with Calcitriol and Phosphate in X-linked Hypophosphatemic Rickets.

Whereas nutritional vitamin D deficient rickets affects many people world-wide, X-linked hypophosphatemic rickets (XLH, MIM 307800) has a prevalence of only 1:25.000. Like other rare diseases burden of disease in XLH and the effect of the current standard of care are inadequately described. Only few height data of untreated patients with XLH have been published. Here we report on height before start of therapy of 127 patients with XLH from 49 centres. One investigator collected all data from patient files documented at regular visits by treating physicians. Height standard deviation score (HSDS) was calculated and the geometrical mean was analysed. At birth all patients had a documented height within the healthy reference population. In this cross-sectional analysis of documented height at time of diagnosis decelerates until a mean age of 4.3 years to a nadir, i.e. lowest HSDS of -3.2 HSDS. Afterwards a spontaneous catch-up growth of +1.3 HSDS occurs until start of puberty. To assess the impact of calcitriol and phosphate supplementation on growth we analysed from a cohort of 18 patients treated at the Dept. of Paediatrics at O.-v.-Guericke-University Magdeburg. In this subgroup, size at birth and all time lowest HSDS (r=0.56 p=0.002) are correlated as well as all time low HSDS and last height during puberty (r=0.62 p=0.001). 10 of 18 patients were treated before age 18 months. Within this group the mean HSDS decelerates to -2.2 SDS at age 4.4 y. and increased to -1.4 SDS at age 9.9 years. Adult height, i.e. mean age 17.6 years was -2.4 HSDS. In conclusion, untreated children with XLR are characterized by normal length at birth, diminished growth rate compared to reference children until 4.3 years and spontaneous catch-up growth of 1.3 HSDS until start of puberty. Improved growth rate in XLR children occured by combined phosphate and calcitriol treatment before 18 months.

Early orthopaedic challenges in haemophilia patients and therapeutic approach.

INTRODUCTION: There is growing evidence that subclinical joint bleeding early in life may lead to subtle changes in joint function, gait, and muscle development in young children with haemophilia. The early identification of such changes provides an opportunity for clinicians to intervene before irreversible structural changes occur. MATERIALS AND METHODS: We have undertaken motion analysis of the knee in 273 children (mean age 9.8 years) with haemophilia A, haemophilia B, or von Willebrand disease and compared the results with those from 200 healthy age- and sex-matched controls (mean age 10.3 years). We have also completed detailed orthopaedic assessments and evaluated overall fitness in most of these children. RESULTS: There was a clear correlation between total motion score and age: r(2)=0.47 for the healthy children and r(2)=0.69 for the haemophilic children. The differences were most striking in children aged 3-4 years. Significant between-group differences were also observed in the comparison of knee bends, gait scores, and rhythmicity. Orthopaedic examinations revealed previously clinically silent pressure pains in the ligaments of the knee joints of 38% of children and in the ligaments and capsule of the ankle joints of 60% of children. The five-item fitness check showed significant deficits relative to controls in overall fitness, endurance, coordination, and flexibility. CONCLUSIONS: Children and adolescents with haemophilia show significant functional impairments relative to normal controls. Early comprehensive assessments of the musculoskeletal system should be made so that individualized physical, physiotherapy, and sports therapy programmes can be developed.

The comparison of cognitive and functional performance in children and Alzheimer's disease supports the retrogenesis model.

The retrogenesis model states that the progression of brain aging and Alzheimer's disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. Our aim was to assess if the progressive decline of cognitive abilities and functional capacity in AD follows an inverse sequence of acquisition compared to normal developmental patterns. One hundred eighty one children ranging in age from 4 to 12 years and 148 adults (cognitively normal, subjects with mild cognitive impairment, and mild-moderately severe AD) were assessed with the same cognitive and functional tools. The statistical analyses showed a progressive and inverse distribution on cognitive, functional, and mental age scores when comparing results of children classified by chronological age and patients by dementia staging. The pattern of cognitive acquisition in children showed a progressive development of overall cognitive function along all age ranges, in addition to a simultaneous acquisition of instrumental and basic daily living activities in the functional domain. AD patients showed a progressive decline in cognitive and functional domains, which concurs with the sequence of impairment reported in this dementia. Our findings provide support to the inverse and progressive pattern of functional and cognitive decline observed in AD patients compared to the developmental acquisition of these capacities in children, as stated by the retrogenesis model. Nonetheless, certain differences should be considered when comparing the sequence of acquisition during ontogenic development with that of progressive loss during the course of AD. Retrogenesis may account for the progressive loss of neocortical-related functions in AD.

Irrigating iris retractor for complicated cataract surgery.

We describe an irrigating iris retractor for cataract surgery in eyes with small pupils. The retractor, a modified irrigating handpiece, has 2 standard side-port irrigating openings and a smooth, button-like iris hook in the front. The hook is inserted into the margin of a small pupil and retracts the pupil peripherally to allow visualization of cortical remnants in the equatorial area of the lens capsule. The capsule can then be safely cleaned using the aspirating handpiece in the surgeon's other hand.

Semantic memory as assessed by the Pyramids and Palm Trees Test: the impact of sociodemographic factors in a Spanish-speaking population.

The objective of this study is to obtain preliminary normative data on the performance the Pyramids and Palm Trees Test (PPT) for a Spanish-speaking population. The effects of age, gender, and educational level on the PPT test were also analyzed. A total of 234 healthy participants, with a broad range of age (18-80 years) and education (1-20 years) performed the three-picture version of the PPT. The mean performance was 51.1 out of 52 possible points (SD=1.3). PPT performance did not vary with age or gender. However, subjects with less than 6 years of formal education scored significantly lower than those with more than 6 years of education though this effect was confounded with age because the group with lower education was also older. Given the ceiling effects of the PPT, further investigation is needed to determine if the visual PPT is sensitive to mild semantic memory impairment.

A preliminary study of the mini-mental state examination in a Spanish child population.

The Mini-Mental State Examination is one of the most widely used screening tests for the adult population in daily neurologic practice. The aim of this study was to describe and to analyze the results of the Mini-Mental State Examination administered to Spanish children and to assess the relationship between Mini-Mental State Examination scores and the child's mental age/intelligence quotient. The study population included 181 children whose ages ranged between 4 and 12 years. The neuropsychologic battery consisted of the Mini-Mental State Examination and Kaufman Brief Intelligence Test. Percentiles were obtained for the Mini-Mental State Examination total score according to age ranges. Performance gradually increased from 4 to 10 years of age when a plateau in the total Mini-Mental State Examination score was reached. At the age of 6 years, results exceeded 24 on average. Pairwise mean comparisons showed statistically significant differences between the age groups (P < .05). Data distribution could be classified in 4 independent groups for the following chronologic ages: 4, 5, and 6 years and from 7 to 12 years of age. The total Mini-Mental State Examination score correlated significantly with the child's chronologic (r = 0.80, P < .001) and mental (r = 0.76, P < .001) ages. This is a preliminary study of the application of the Mini-Mental State Examination in a Spanish child population as well as a first step for the assessment of the usefulness of this instrument as a cognitive screening tool for children's development.

Cross-national comparison and validation of the Alzheimer's Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID).

BACKGROUND: The Alzheimer's Disease Assessment Scale (ADAS) is often used in international multicenter trials. Use across countries presupposes correct translation and adaptation of the scale, and maintenance of its psychometric properties. OBJECTIVES: To compare the various translations of the ADAS used in Western Europe, to design internationally harmonized translations and to validate these. SETTING: International cooperative study in eight European countries. METHODS: An inventory was made of existing versions of the ADAS-Cog used in eight European countries, and adaptations were made. The concurrent validity of the harmonized versions of the ADAS was tested in 283 patients with probable or possible Alzheimer's disease. The Nurses Observation Scale for Geriatrics (NOSGER), CAMCOG-R and MMSE was used to assess concordance between cognitive and behavioral measures. RESULTS: Differences between the versions mainly involved object naming, items for verbal memory, such as the number of trials allowed, the imagery value of the words selected as targets or distractors, and the number of parallel versions. These differences were eliminated by adapting and harmonizing the various versions of the ADAS-Cog. Thereafter, only small differences between the different countries were found, and patterns of correlation between ADAS-Cog, and the NOSGER, CAMCOG-R and MMSE were consistent. CONCLUSIONS: The study underlines the need to use harmonized versions of instruments for rating dementia in multinational studies. The findings indicate that the harmonization of the ADAS-Cog was successful.