Ankylosing spondylitis: genomic and functional characterization of candidate genes and their repercussion in clinical practice

RESUMO: Introdução: A espondilite anquilosante (EA) é uma doença inflamatória crónica caracterizada pela inflamação das articulações sacroilíacas e da coluna. A anquilose progressiva motiva uma deterioração gradual da função física e da qualidade de vida. O diagnóstico e o tratamento precoces podem contribuir para um melhor prognóstico. Neste contexto, a identificação de biomarcadores, assume-se como sendo muito útil para a prática clínica e representa hoje um grande desafio para a comunidade científica. Objetivos: Este estudo teve como objetivos: 1 - caracterizar a EA em Portugal; 2 - investigar possíveis associações entre genes, MHC e não-MHC, com a suscetibilidade e as características fenotípicas da EA; 3 - identificar genes candidatos associados a EA através da tecnologia de microarray. Material e Métodos: Foram recrutados doentes com EA, de acordo com os critérios modificados de Nova Iorque, nas consultas de Reumatologia dos diferentes hospitais participantes. Colecionaram-se dados demográficos, clínicos e radiológicos e colhidas amostras de sangue periférico. Selecionaram-se de forma aleatória, doentes HLA-B27 positivos, os quais foram tipados em termos de HLA classe I e II por PCR-rSSOP. Os haplótipos HLA estendidos foram estimados pelo algoritmo Expectation Maximization com recurso ao software Arlequin v3.11. As variantes alélicas dos genes IL23R, ERAP1 e ANKH foram estudadas através de ensaios de discriminação alélica TaqMan. A análise de associação foi realizada utilizando testes da Cochrane-Armitage e de regressão linear, tal como implementado pelo PLINK, para variáveis qualitativas e quantitativas, respetivamente. O estudo de expressão génica foi realizado por Illumina HT-12 Whole-Genome Expression BeadChips. Os genes candidatos foram validados usando qPCR-based TaqMan Low Density Arrays (TLDAs). Resultados: Foram incluídos 369 doentes (62,3% do sexo masculino, com idade média de 45,4 ± 13,2 anos, duração média da doença de 11,4 ± 10,5 anos). No momento da avaliação, 49,9% tinham doença axial, 2,4% periférica, 40,9% mista e 7,1% entesopática. A uveíte anterior aguda (33,6%) foi a manifestação extra-articular mais comum. Foram positivos para o HLA-B27, 80,3% dos doentes. Os haplótipo A*02/B*27/Cw*02/DRB1*01/DQB1*05 parece conferir suscetibilidade para a EA, e o A*02/B*27/Cw*01/DRB1*08/DQB1*04 parece conferir proteção em termos de atividade, repercussão funcional e radiológica da doença. Três variantes (2 para IL23R e 1 para ERAP1) mostraram significativa associação com a doença, confirmando a associação destes genes com a EA na população Portuguesa. O mesmo não se verificou com as variantes estudadas do ANKH. Não se verificou associação entre as variantes génicas não-MHC e as manifestações clínicas da EA. Foi identificado um perfil de expressão génica para a EA, tendo sido validados catorze genes - alguns têm um papel bem documentado em termos de inflamação, outros no metabolismo da cartilagem e do osso. Conclusões: Foi estabelecido um perfil demográfico e clínico dos doentes com EA em Portugal. A identificação de variantes génicas e de um perfil de expressão contribuem para uma melhor compreensão da sua fisiopatologia e podem ser úteis para estabelecer modelos com relevância em termos de diagnóstico, prognóstico e orientação terapêutica dos doentes. -----------ABSTRACT: Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints leading to progressive joint ankylosis and in progressive deterioration of physical function and quality of life. An early diagnosis and early therapy may contribute to a better prognosis. The identification of biomarkers would be helpful and represents a great challenge for the scientific community. Objectives: The present study had the following aims: 1- to characterize the pattern of AS in Portuguese patients; 2- to investigate MHC and non-MHC gene associations with susceptibility and phenotypic features of AS and; 3- to identify candidate genes associated with AS by means of whole-genome microarray. Material and Methods: AS was defined in accordance to the modified New York criteria and AS cases were recruited from hospital outcares patient clinics. Demographic and clinical data were recorded and blood samples collected. A random group of HLA-B27 positive patients and controls were selected and typed for HLA class I and II by PCR-rSSOP. The extended HLA haplotypes were estimated by Expectation Maximization Algorithm using Arlequin v3.11 software. Genotyping of IL23R, ERAP1 and ANKH allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests as implemented in PLINK, for dichotomous and quantitative variables, respectively. Gene expression profile was carried out using Illumina HT-12 Whole-Genome Expression BeadChips and candidate genes were validated using qPCR-based TaqMan Low Density Arrays (TLDAs). Results: A total of 369 patients (62.3% male; mean age 45.4±13.2 years; mean disease duration 11.4±10.5 years), were included. Regarding clinical disease pattern, at the time of assessment, 49.9% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopathic disease. Acute anterior uveitis (33.6%) was the most common extra-articular manifestation. 80.3% of AS patients were HLA-B27 positive. The haplotype A*02/B*27/Cw*02/DRB1*01/DQB1*05 seems to confer susceptibility to AS, whereas A*02/B*27/Cw*01/DRB1*08/DQB1*04 seems to provide protection in terms of disease activity, functional and radiological repercussion. Three markers (two for IL23R and one for ERAP1) showed significant single-locus disease associations. Association of these genes with AS in the Portuguese population was confirmed, whereas ANKH markers studied did not show an association with AS. No association was seen between non-MHC genes and clinical manifestations of AS. A gene expression signature for AS was established; among the fourteen validated genes, a number of them have a well-documented inflammatory role or in modulation of cartilage and bone metabolism. Conclusions: A demographic and clinical profile of patients with AS in Portugal was established. Identification of genetic variants of target genes as well as gene expression signatures could provide a better understanding of AS pathophysiology and could be useful to establish models with relevance in terms of susceptibility, prognosis, and potential therapeutic guidance.

Efetividade da intervenção conservadora e de um programa de exercício físico no solo na osteoartrose do joelho

RESUMO: Objectivo: O estudo do efeito da fisioterapia e do exercício em diversos indicadores relacionados com a osteoartrose do joelho tem evidenciado efeitos benéficos em utentes com esta condição. Nesta sequência, pretendeu-se avaliar a efetividade da intervenção conservadora em conjunto com um programa de exercícios ao nível da dor, rigidez, amplitude articular, função física e qualidade de vida em utentes com osteoatrose do joelho a curto prazo, quando comparado com a intervenção recomendada. A prática clínica atual em Portugal, sob prescrição, desenvolve-se de acordo com o padrão que se pretende investigar. Metodologia: Trata-se de um estudo quasi-experimental controlado e sem aleatorização. Os utentes da Clínica FPM (n=20; 35,0% homens, 65,0% mulheres) sujeitos à intervenção conservadora (calor húmido, ultra-som e massagem) em conjunto com um programa de exercício no solo, durante um período de 4 semanas com frequência diária, integram o grupo experimental e os utentes inscritos no programa de exercício a solo do “Viver Activo” no Leirisport (n=21; 23,8% homens, 76,2% mulheres), num período de 8 semanas com frequência bi-semanal são considerados como grupo de controlo. Os instrumentos de medida aplicados foram o Knee Outcome Osteoarthritis Score (KOOS) para os outcomes dor, rigidez, função física e qualidade de vida e a goniometria para a amplitude articular. Resultados: Em ambos os grupos foram observados aumentos significativos em todos os outcomes avaliados pelo KOOS (dor, rigidez, função física e qualidade de vida) e pela goniometria (amplitude articular) num período de 4 e 8 semanas. Quando comparada a evolução do grupo experimental com a do grupo controlo, verifica-se que as diferenças significativas ocorrem na flexão (p <0,05) (maior evolução para o grupo experimental), e na dor (p <0,05) (maior evolução para o grupo controlo). Nos outcomes rigidez, função física e qualidade de vida foi ainda possível identificar resultados positivos que sugerem possíveis benefícios da intervenção em grupo para os sujeitos a ela submetidos. Discussão e Conclusão: Estes resultados sugerem que a intervenção clínica individualizada é mais efectiva do que a intervenção em grupo no aumento da amplitude articular do joelho em utentes com osteoartrose a curto prazo. No entanto, para os outcomes dor, rigidez, função física e qualidade de vida, a intervenção em grupo parece ser clinicamente e estatisticamente melhor. A relevância deste estudo afirma-se ao demonstrar que utentes com osteoartrose do joelho que integrem um programa de exercício em grupo beneficiam de melhorias importantes. Ao adicionar sessões de fisioterapia para realização de intervenção conservadora individualizada e exercícios supervisionados agrega um maior alívio sintomático.-------- ABSTRACT: Study of physical therapy and exercise into several indicators associated to knee osteoarthritis has shown positive effects in subjects within this condition. According to the study it has been evaluated the effectiveness of a conservative intervention along with a exercise program directed to pain, stiffness, range of motion, physical function and quality of life of patients with knee osteoarthritis in a short term when compared with the recommended intervention. Under prescription the current clinical practice in Portugal is developed according to the pattern to investigate. Methodology: This is a quasi-experimental controlled study without randomization. The subjects of FPM Clinic (n= 20, 35.0% men, 65.0% women) were submitted to the conservative intervention (hot pack, ultrasound and massage) with a land exercise program during a 4 week-period (all-weekly) were assigned in the experimental group. Patients signed in the land exercise program of "Active Living" in Leirisport (n = 21, 23.8% men, 76.2% women) a 8 week-period (bi-weekly) were assigned as control group. Outcomes were measured by the Knee Outcome Osteoarthritis Score (KOOS) for pain, stiffness, physical function and quality of life. Goniometry was used for range of motion. Results: Both treatment groups obtained successful outcomes measured by significant reductions in KOOS scores and improvement in goniometry in a 4 and 8-week period. When compared the evolution of the experimental group with the control group it appears that significant differences occur in the range of motion (p <0.05) (further progress in the experimental group), and pain (p <0.05) (further evolution for the control group). In outcomes stiffness, physical function and quality of life was possible to identify positive results that suggest potential benefits of intervention for the submitted subjects. Discussion and Conclusion: These results suggest that individualized clinical intervention is more effective than group intervention in range of motion improving in patients with knee osteoarthritis in a 4-week period. However outcomes for pain, stiffness, physical function and quality of life appear to be clinically and statistically better for the group intervention. The significance of this study is essencial because it demonstrates that patients with knee osteoarthritis who incorporate an exercise program in group reveal improvements. When adding physical therapy sessions with individual conservative intervention and supervised exercises the result is an improvement of symptomatic relief.

Efectividade de um programa de exercício aquático na osteoartrose do joelho

RESUMO: A osteoartrose do joelho é uma condição clínica cuja prevalência tem aumentado nos últimos anos na população idosa. Trata-se de uma condição que pode ser bastante incapacitante para o idoso, gerando um forte impacto social e económico. O exercício aquático tem sido identificado como um factor de promoção da melhoria do quadro clínico nesta população, mas a sua efectividade não está, ainda, determinada. Objectivo: investigar a efectividade, a curto e médio prazo, de um programa de exercício aquático, realizado em grupo, com a duração de 8 semanas, na amplitude articular, dor e rigidez do joelho, e na função física e qualidade de vida, em idosos com osteoartrose do joelho. Metodologia: Recorreu-se a um estudo quase-experimental, double-blind, controlado, sem aleatorização, cuja amostra, constituída por 43 sujeitos, foi selecionada por conveniência. Os sujeitos do grupo experimental (n=22) foram submetidos ao programa de exercício aquático e os do grupo de controlo (n=21) foram submetidos ao programa de exercício no solo. Ambos os programas foram definidos de acordo com as recomendações internacionais para a prática de exercício físico em idosos com osteoartrose (Arthritis Foundation, 2009a, 2009b). Todo o grupo foi avaliado no início do programa, no final do mesmo (8 semanas) e após 6 semanas de follow-up, nos seguintes indicadores: amplitude articular do joelho (através do goniómetro), dor, rigidez, função e qualidade de vida (através do KOOS). Resultados: A amostra deste estudo foi constituída por sujeitos maioritariamente do género feminino (76,7%), com uma média de 72,7 anos (DP=5,49). O programa de exercício aquático implementado demonstrou um aumento da amplitude articular passiva de flexão (p<0,0001) e extensão (p=0,016) do joelho, uma diminuição da dor e da rigidez articular (p<0,0001), um aumento da função nas AVD’s (p<0,0001) e no desporto/lazer (p=0,031), e ainda, um aumento da qualidade de vida (p<0,0001). Contudo, apenas os níveis de amplitude articular passiva de extensão do joelho (p=0,083) e de função no desporto/lazer (p=0,244) se mantiveram ao longo das seis semanas de follow-up. Conclusões: Apesar de algumas limitações, considera-se que este estudo é de grande importância para a comunidade científica e para os fisioterapeutas preocupados com a crescente prevalência da osteoartrose e dos custos associados. O exercício aquático parece ser uma estratégia importante na melhoria do estado de saúde dos idosos com osteoartrose do joelho.----------------- ABSTRACT: The osteoarthritis of the knee is a clinical condition that has been increasing among the elderly population over the past few years. It’s a condition that can be fairly disabling to the elderly individual, and which generates a strong social and economic impact. Aquatic exercise has been named as a promotional factor in the improvement of the clinical picture in this population, but its effectiveness is yet to be determined. Objective: To investigate the effectiveness, in a short and medium term, of an aquatic exercise program undertaken by a group over eight weeks, in the joint amplitude, pain and stiffness of the knee, and in the physical function and quality of life in elderly people who suffer from knee osteoarthritis. Methodology: was used a double-blind, quasi-experimental study with no randomization and its 43 subjects were selected as a matter of convenience. The subjects of the experimental group (n=22) were subjected to an aquatic exercise program and those of the control group (n=21) were subjected to a land-based exercise program. Both programs have followed international recommendations on the practice of physical exercise in elderly people who suffer from osteoarthritis (Arthritis Foundation, 2009a, 2009b). The entire group was evaluated in the beginning and at the end of the program (8 weeks later), and after a 6 week follow-up, in these parameters: knee range of motion (through a goniometer), pain, stiffness, function and quality of life (through KOOS). Results: This sample was predominantly female (76,7%) with a mean age of 72,7 years (SD=5,49). Aquatic exercise resulted in increase of passive joint flexion (p<0,0001) and knee extension (p=0,016), in the decline of pain and stiffness (p<0,0001), in the increase of function in the ADLs (p<0,0001). However, only the knee extension amplitude (p=0,083) and the function in sports/leisure (p=0,244) were kept through the six-week follow-up. Conclusions: Despite some limitations, this study is of great importance to the community and to the physiotherapists concerned with the growing prevalence of osteoarthritis and the associated costs. Aquatic exercise appears to be an important strategy in the improvement of the health condition of patients who suffer from knee osteoarthritis.

The optimum size of the portuguese public hospital

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

As necessidades e redes de apoio de famílias de pessoas com perturbação do espectro do autismo

RESUMO: O objectivo do presente estudo consistiu em avaliar as necessidades de apoio de 63 pais com filhos (crianças, jovens ou adultos) com Perturbação do Espectro Autista (PEA), no que diz respeito a: (1) necessidades de apoio identificadas pelos pais, (2) redes de suporte destes pais e (3) relação entre necessidades de apoio e características dos pais e filhos. Todos os pais tinham participado no 1º nível do projecto nacional intitulado “Oficinas de Pais/Bolsas de Pais” – o Grupo de Apoio Emocional (GAE). No sentido de verificar se ocorreram mudanças nas suas necessidades de apoio, avaliou-se o antes (momento I) e o depois do GAE (momento II). Utilizou-se a Escala de Funções de Apoio Social (Dunst, Trivette, & Deal, 1988) para avaliar as necessidades de apoio e a Escala de Apoio Social (Dunst, Trivette, & Deal, 1988) para avaliar as redes de apoio social. Os resultados demonstram que os pais de pessoas com PEA apresentam (tanto antes como após a frequência nas oficinas do GAE) sobretudo necessidades de apoio de carácter emocional e profissional, e menos necessidades de carácter prático. Para suprir as necessidades de apoio, antes e após o GAE, estes pais recorreram, numa primeira opção, ao cônjuge, aos profissionais e posteriormente aos amigos. Os vizinhos constituíram a rede de apoio social a quem menos recorreram. Apesar de algumas diferenças observadas entre o momento I e momento II, estas não foram estatisticamente significativas nem para as necessidades de apoio, nem para as redes de apoio social.------------------------- ABSTRACT: The study aimed to evaluate the support needs of 63 parents of children, adolescents and adults with Autistic Spectrum Disorder (ASD), concerning three aspects: (1) support needs that parents identified as major target, (2) social support network of these parents, and (3) the relationship between support needs and parent and children characteristics. All parents had participated in the first level of the national project “Oficinas de Pais/Bolsas de Pais” - the Emotional Support Group (ESG). In order to verify if any changes occurred in the needs of support, evaluation was carried before (moment I) and after (moment II) the ESG. In this context, parents filled the Supports Function Scale (Dunst, Trivette, & Deal, 1988), which evaluated their different needs of support, and also the Social Supports Scale (Dunst, Trivette & Deal, 1988) which in turn evaluated their social support network. The results showed that parents of children with ASD, both before and after the ESG, revealed emotional and professional needs and, in a less extent, also practical needs. To address the referred needs (before and after the ESG) these parents seek in the first place the support of their spouse, then that of professionals and, later on, that of friends. Neighbours are the support that parents least address. Despite some observed differences in support needs and social support networks between the two moments, these were, however, not statistically significant.

Attachment to parents: the mediating role of inhibition of exploration and individuality on health behaviors

This study’s goal was to analyze whether the quality of university students’ relationship with their parents mediated the association between mental health and physical symptoms and health behavior. Participants were 250 university students (66% female and 34% male), aged between 17 and 29 years old (M = 20.88, SD = 2.03) that answered the Father/Mother Attachment Questionnaire (FMAQ), the Physical Symptoms Scale from the Rotterdam Symptom Checklist (RSCL), the Health Behavior Questionnaire (HBQ), and the Hospital Anxiety and Depression Scale (HADS). The results showed that the indirect effect of physical symptoms on health behavior was significantly mediated by the father’s and mother’s inhibition of exploration and individuality (IEI). Also the indirect effect of psychological distress on health behavior was significantly mediated by the father’s and mother’s IEI. These results suggest that young adults who had more restrictions to their individuality show worse health behaviors. Separation Anxiety and Dependence (SAD) and Quality of Emotional Bond (QEB), the other 2 attachment scales, were not mediators of the relationship between physical symptoms/ psychological distress and health behavior. This study shows the importance of promoting positive parenting practices that contribute to healthier behavior choices and less risky behaviors, as well as the need for more studies that clearly identify these practices in young adult populations.

Evidence for validity and reliability of a french version of the FAAM.

BACKGROUND: The Foot and Ankle Ability Measure (FAAM) is a self reported questionnaire for patients with foot and ankle disorders available in English, German, and Persian. This study plans to translate the FAAM from English to French (FAAM-F) and assess the validity and reliability of this new version.METHODS: The FAAM-F Activities of Daily Living (ADL) and sports subscales were completed by 105 French-speaking patients (average age 50.5 years) presenting various chronic foot and ankle disorders. Convergent and divergent validity was assessed by Pearson's correlation coefficients between the FAAM-F subscales and the SF-36 scales: Physical Functioning (PF), Physical Component Summary (PCS), Mental Health (MH) and Mental Component Summary (MCS). Internal consistency was calculated by Cronbach's Alpha (CA). To assess test re-test reliability, 22 patients filled out the questionnaire a second time to estimate minimal detectable changes (MDC) and intraclass correlation coefficients (ICC).RESULTS: Correlations for FAAM-F ADL subscale were 0.85 with PF, 0.81 with PCS, 0.26 with MH, 0.37 with MCS. Correlations for FAAM-F Sports subscale were 0.72 with PF, 0.72 with PCS, 0.21 with MH, 0.29 with MCS. CA estimates were 0.97 for both subscales. Respectively for the ADL and Sports subscales, ICC were 0.97 and 0.94, errors for a single measure were 8 and 10 points at 95% confidence and the MDC values at 95% confidence were 7 and 18 points.CONCLUSION: The FAAM-F is valid and reliable for the self-assessment of physical function in French-speaking patients with a wide range of chronic foot and ankle disorders.

Health-related quality of life in survivors of childhood cancer: the role of chronic health problems.

INTRODUCTION: The influence of specific health problems on health-related quality of life (HRQoL) in childhood cancer survivors is unknown. We compared HRQoL between survivors of childhood cancer and their siblings, determined factors associated with HRQoL, and investigated the influence of chronic health problems on HRQoL. METHODS: Within the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976-2005 aged <16 years. Siblings received similar questionnaires. We assessed HRQoL using Short Form-36 (SF-36). Health problems from a standard questionnaire were classified into overweight, vision impairment, hearing, memory, digestive, musculoskeletal or neurological, and thyroid problems. RESULTS: The sample included 1,593 survivors and 695 siblings. Survivors scored significantly lower than siblings in physical function, role limitation, general health, and the Physical Component Summary (PCS). Lower score in PCS was associated with a diagnosis of central nervous system tumor, retinoblastoma or bone tumor, having had surgery, cranio-spinal irradiation, or bone marrow transplantation. Lower score in Mental Component Summary was associated with older age. All health problems decreased HRQoL in all scales. Most affected were survivors reporting memory problems and musculoskeletal or neurological problems. Health problems had the biggest impact on physical functioning, general health, and energy and vitality. CONCLUSIONS: In this study, we showed the negative impact of specific chronic health problems on survivors' HRQoL. IMPLICATIONS FOR CANCER SURVIVORS: Therapeutic preventive measures, risk-targeted follow-up, and interventions might help decrease health problems and, consequently, improve survivors' quality of life.

Rapid Improvement In Health-Related Quality Of Life In Gouty Arthritis Patients Treated With Canakinumab (Acz885) Compared To Triamcinolone Acetonide

Background : Canakinumab, a fully human anti-IL-1b antibody has been shown to control inflammation in gouty arthritis. This study evaluated changes in health-related quality of life (HRQoL) in patients treated with canakinumab or triamcinolone acetonide (TA).Methods : An 8-wk, dose-ranging, active controlled, single-blind study in patients (_18 to _80 years) with acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150mg sc or TA 40mg im. HRQoL was assessed using patient reported outcomes evaluating PCS and MCS, and subscale scores of SF-36_ [acute version 2]) and functional disability (HAQ-DI_).Results : In canakinumab 150mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved in 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) and at 8 wks improved to 86.1 and 86.6 (mean increases of 44.6 and 50.6); these were higher than levels seen in the general US population. TA group, showed less improvement in 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain). Functional disability scores, measured by the HAQ-DI_ decreased in both treatment groups (Table 1).Conclusions : Gouty arthritis patients treated with canakinumab showed a rapid improvement in physical and mental well-being based on SF-36_ scores. In contrast to the TA group, patients treated with canakinumab showed improvement in 7 days in physical function and bodily pain approaching levels of the general population.Disclosure statement : U.A., A.F., V.M., D.R., P.S. and K.S. are employees and shareholders of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support and consultancy fees from Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and EnzymeRx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultation fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group.

New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance- and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, ≥1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults who have acute or chronic diseases need even more dietary protein (ie, 1.2-1.5 g/kg body weight/d). Older people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73m(2)), but who are not on dialysis, are an exception to this rule; these individuals may need to limit protein intake. Protein quality, timing of ingestion, and intake of other nutritional supplements may be relevant, but evidence is not yet sufficient to support specific recommendations. Older people are vulnerable to losses in physical function capacity, and such losses predict loss of independence, falls, and even mortality. Thus, future studies aimed at pinpointing optimal protein intake in specific populations of older people need to include measures of physical function.

Rapid Improvement in Health-Related Quality of Life (HRQoL) in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gouty arthritis is a painful inflammatory disease with a significant impact on patients' HRQoL. In gouty arthritis, the inflammatory response is initiated by interleukin-1b (IL-1b) release, due to activation of the NALP3 inflammasome by MSU crystals. Canakinumab, a fully human anti-IL-1b antibody has a long half-life and has been shown to control inflammation in gouty arthritis. This study evaluated changes in HRQoL in gouty arthritis patients following treatment with canakinumab or triamcinolone acetonide (TA).Methods: This was an 8-week, dose-ranging, multi-center, active controlled, single-blind study. Patients (>=18 to <=80 years) experiencing an acute gouty arthritis flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to canakinumab 10, 25, 50, 90, 150 mg sc or TA 40 mg im. HRQoL was assessed as an exploratory endpoint at baseline and different pre-specified time-points using patient reported outcomes evaluating general mental and physical component summary scores and subscale scores of SF-36® (acute version 2) and functional disability (HAQ-DI©). We report HRQoL results for canakinumab 150 mg, the dose that was selected for the Phase III studies.Results: Baseline assessments showed a major impact on the HRQoL during acute gouty arthritis. Compared to TA, canakinumab 150 mg showed greater improvements in SF-36® physical and mental component summary and subscale scores at 7 days post-dose.In the canakinumab 150 mg group, the most severe impairment at baseline was reported for physical functioning and bodily pain; levels of 41.5 and 36.0, respectively, which improved within 7 days to 80.0 and 72.2 (mean increases of 39.0 and 35.6) approaching levels of the general US population (84.2 and 75.2). 8 weeks post-dose patients reached levels of 86.1 and 86.6 (mean increases of 44.6 and 50.6 for physical functioning and bodily pain, respectively) and these were higher than levels seen in the general US population. This was in contrast to patients treated with TA, who showed less improvement within 7 days (mean increases of 23.3 and 21.3 for physical function and bodily pain, respectively). None of the scores reached levels of the general US population 8 weeks post-dose. Functional disability scores, as measured by the HAQ-DI© decreased in both treatment groupsConclusions: All canakinumab doses showed a rapid improvement in physical and mental well-being of gouty arthritis patients based on SF-36® scores, in particular the 150 mg dose. In contrast to the TA group, patients treated with canakinumab showed improvement within 7 days in physical function and bodily pain approaching levels of the general population. The 150 mg dose of canakinumab was selected for further development in Phase III studies.

Subclinical hypothyroidism and functional mobility in older adults.

BACKGROUND: Health risks associated with subclinical hypothyroidism in older adults are unclear. Our objective was to compare the functional mobility of people aged 70 to 79 years by thyroid function categorized by thyrotropin (TSH) level as euthyroid (>or=0.4 to <4.5 mIU/L), mild subclinical hypothyroid (>or=4.5 to <7.0 mIU/L), or moderate subclinical hypothyroid (>or=7.0 to <or=20.0 mIU/L with a normal free thyroxine level) cross-sectionally and over 2 years. METHODS: A total of 2290 community-dwelling residents participating in the year 2 clinic visit (July 1998-June 1999) of the Health, Aging, and Body Composition (Health ABC) Study, who had measured TSH level, had the capacity to walk 20 m unaided, and were not taking thyroid medication or had TSH levels consistent with hyperthyroidism or hypothyroidism. Main outcome measures included self-reported and performance-based measures of mobility (usual and rapid gait speed and endurance walking ability) assessed at study baseline (year 2) and 2 years later. RESULTS: In age- and sex-adjusted analyses, the mild subclinical hypothyroid group (vs the euthyroid group) demonstrated better mobility (faster mean usual and rapid gait speed [1.20 vs 1.15 m/s and 1.65 vs 1.56 m/s, respectively; P < .001] and had a higher percentage of those with good cardiorespiratory fitness and reported walking ease [39.2% vs 28.0% and 44.7% vs 36.5%, respectively; P < .001]). After 2 years, persons with mild subclinical hypothyroidism experienced a similar decline as the euthyroid group but maintained their mobility advantage. Persons with moderate subclinical hypothyroidism had similar mobility and mobility decline as the euthyroid group. CONCLUSION: Generally, well-functioning 70- to 79-year-old individuals with subclinical hypothyroidism do not demonstrate increased risk of mobility problems, and those with mild elevations in TSH level show a slight functional advantage.

Estratigrafía secuencial de sistemas deltaicos en cuencas de antepaís: ejemplos de Montserrat, Sant Llorenç del Munt, Montserrat y Roda (Paleogeno, cuenca de Antepaís surpirenaica).

After the sedimentological study of the Sant Llorenc del Munt, Montserrat and Roda deltaic systems, a stratigraphic subdivision based on three different scale transgressiveregressive sequences has been developed. This subdivision has been established on the coastal facies belts from the deduced shoreline (and associated facies belts) migration. These transgressive-regressive sequences are formed by a lower transgressive part with a deepening-upwards trend and a retrogradational staclung pattern and an upper regressive part, with shallowing-upwards trend and a progradational stacking pattern. The lowest scale sequences (metrical) have been named 'fundamental sequences'. A series of 'composite sequences', intermediate scale (decametric to hectometric), have been defined afier the study of the staclung pattem of the fundamental sequences. After the study of the stacking pattem of composite sequences there have been defined a series of large-scale (decametric to kilometric) 'composite megasequences'.

L'impacte d'un programa de tennis com a eina de millora de la qualitat de vida i l'estrès percebut en dones físicament inactives d'entre 43 i 50 anys

Introducció: L’activitat física és una necessitat imprescindible per a la salut de les persones, i tot i ser conscients dels seus beneficis encara es troben alts percentatges d’inactivitat física i sedentarisme. Per aquest motiu, els objectius principals d’aquest estudi són esbrinar si les dones adultes d’entre 43 i 50 anys que realitzen activitat física regularment, més concretament que practiquen l’esport del tennis, tenen una qualitat de vida i un estrès percebut millor que les que no realitzen activitat física, i per tant, valorar l’impacte d’un programa de tennis adequat i específic, és a dir, adaptat a les característiques i les necessitats dels alumnes, com a eina per millorar aquestes dues variables: l’estrès percebut i la qualitat de vida. Metodologia: El treball és un estudi experimental el qual consta d’una mostra total de 12 dones, 6 es varen assignar al grup control (practiquen el tennis) i 6 al grup intervenció (no realitzen AF), i totes elles de manera aleatòria. Les participants del grup intervenció varen realitzar un programa de 8 sessions de 60 minuts de treball durant 4 setmanes, mentre que les participants del grup control van seguir la seva rutina habitual. Les variables dependents (qualitat de vida i estrès percebut) es varen mesurar abans i després de la intervenció. Resultats: Els resultats obtinguts mostren, pel que fa al grup intervenció, millores significatives respecte a les dues variables mentre que el grup control presenta alguna mínima millora puntual però, en general no es produeixen canvis. Quan a la variable de qualitat de vida, les participants del grup intervenció han obtingut millores en les 8 dimensions del qüestionari un cop finalitzat el programa, les quals han estat més significatives pel que fa al rol emocional i la funció física. I respecte a l’estrès percebut, el grup intervenció ha aconsegui reduir el seu nivell d’estrès 3’17 punts. Discussió: Per tant, podem dir que el tennis, amb el disseny adequat d’un programa, millora l’estat de salut de les persones, en aquest cas redueix l’estrès percebut i millora la qualitat de vida. Extretes les conclusions i coneixent l’elevat nombre de dones que practiquen el tennis és de gran interès i molt factible oferir aquest programa a clubs de tennis amb l’objectiu de millorar la salut de les persones.

Elämänlaatu ja iäkkäiden kaatumisten ehkäisy

Quality of life and fall prevention among the aged Improvement of quality of life is considered to be one of the most important goals of prevention, treatment and rehabilitation among the aged. The study aimed to describe and assess fall prevention interventions as a quality of life indicator, and to describe the social dimension of health-related quality of life among the aged. In addition, it aimed to assess the effects of fall prevention intervention on quality of life among the aged. The study was implemented by using a methodological triangulation. The data in the systematic review was retrieved from the databasis of medical and nursing sciences. Home-dwelling aged (n=19) participated in the qualitative study of a social dimension of quality of life. The data was gathered by the thematic interview method. The quantitative multifactorial fall prevention study comprised 591 participants, either the aged living at home or in sheltered housing, showing an increased risk of falling. Participants were randomized into an intervention or a control group. Follow-up measurements were carried out after a 12 month intervention. The data was collected by the 15D quality of life instrument and a structured questionnaire. Based on the systematic review, only in a few studies fall prevention produced positive effects on dimensions of quality of life (physical function, social function, vitality, mental health, environmental domain). Based on the thematic interview the social dimension of quality of life consisted of three themes: personal values, personal milieu and personal daily life. Based on the fall prevention program, depressive symptoms and distress decreased, managing in usual activities improved, sexual activity and phone contacts increased among men. In women, managing in usual activities improved, socializing increased and discomfort and symptoms decreased. Within the groups, self-perceived health improved among women in the intervention group and among men in the control groups. In addition, fear of falling and feelings of insecurity reduced among women in the intervention group. Personal daily life with its activities opened up new perspectives into the social dimension of good quality of life, which was emphasized especially in the interviews of the oldest participants. Multifactorial fall prevention can affect positively some physical and psychosocial dimensions of quality of life among the community-dwelling aged. Additional studies with larger sample sizes, longer follow-up periods and multiple outcome measures are needed. Fall prevention intervention may affect quality of life by different mechanisms, and the quantitative and qualitative assessment of its effects should also be included in the interventions of randomized controlled trials.