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P. 190-192, advertisements.

Review of the long-term disability associated with hip fractures

Objectives To determine the proportion of hip fracture patients who experience long-term disability and to re-estimate the resulting burden of disease associated with hip fractures in Australia in 2003. Methods A literature review of the functional outcome following a hip fracture (keywords: morbidity, treatment outcome, disability, quality of life, recovery of function, hip fractures, and femoral neck fractures) was carried out using PubMed and Ovid MEDLINE. Results A range of scales and outcome measures are used to evaluate recovery following a hip fracture. Based on the available evidence on restrictions in activities of daily living, 29% of hip fracture cases in the elderly do not reach their pre-fracture levels 1 year post-fracture. Those who do recover tend to reach their pre-fracture levels of functioning at around 6 months. These new assumptions result in 8251 years lived with disability for hip fractures in Australia in 2003, a 4.5-fold increase compared with the previous calculation based on Global Burden of Disease assumptions that only 5% of hip fractures lead to long-term disability and that the duration of short-term disability is just 51 days. Conclusions The original assumptions used in burden of disease studies grossly underestimate the long-term disability from hip fractures. The long-term consequences of other injuries may similarly have been underestimated and need to be re-examined. This has important implications for modelling the cost-effectiveness of preventive interventions where disability-adjusted life years are used as a measure of health outcome.

Functional and psychosocial outcomes 1 year after mild stroke

Background Mild stroke survivors are generally discharged from acute care within a few days of the stroke event, often without rehabilitation follow-up. We aimed to examine the recovery trajectory for male patients and their wife-caregivers during the 12 months postdischarge. Methods A descriptive study was undertaken to examine functional outcomes, quality of life (QOL), depression, caregiver strain, and marital function in a prospective cohort of male survivors of mild stroke and their wife-caregivers during the 12 months postdischarge. Data from each point in time were summarized and repeated measures analyses undertaken. Logistic regression was used to determine which baseline demographic and biopsychosocial variables influenced or predicted marital functioning 1 year postdischarge. Results A total of 38 male patients (mean age 63.4 years) and their wife-caregivers (mean age 58.5 years) were examined. The median discharge National Institutes of Health Stroke Scale score was 1.5, modified Rankin Scale score was 1.0, Barthel Index was 100.0, and Stroke Impact Scale-16v2 score was 78.5. The patients' modified Rankin Scale (function) and QOL scores improved significantly over time (F (2) = 4.583, P = .017; and F (6) = 5.632, P < .001, respectively). However, the wife-caregiver QOL scores did not change. Multivariate analysis revealed overall worsening of depression for both the patient and wife-caregivers (F (6, 32) = 3.087, P = .017) and marital function (F (6, 32) = 3.961, P = .004), although the wife-caregivers' perceptions of caregiver strain improved (F (6, 32) = 3.923, P = .007). None of the measured variables were associated with marital functioning 1 year postdischarge. Conclusions Despite improvement in patients' functional status, other patient and wife-caregiver psychosocial outcomes during the 12 months postdischarge may be negatively affected. Thus, attention needs to focus on recovery beyond functional outcomes.

Long-term growth and anthropometry after childhood liver transplantation

Objectives: To describe longitudinal height, weight, and body mass index changes up to 15 years after childhood liver transplantation. Study design: Retrospective chart review of patients who underwent liver transplant from 1985-2004 was performed. Subjects were age <18 years at transplant, survived ≥5 years, with at least 2 recorded measurements, of which one was ≥5 years post-transplant. Measurements were recorded pre-transplant, 1, 5, 10, and 15 years later. Results: Height and weight data were available in 98 and 104 patients, respectively; 47% were age <2 years at transplant; 58% were Australian, and the rest were from Japan. Height recovery continued for at least 10 years to reach the 26th percentile (Z-score -0.67) 15 years after transplant. Australians had better growth recovery and attained 47th percentile (Z-score -0.06) at 15 years. Weight recovery was most marked in the first year and continued for 15 years even in well-nourished children. Growth impaired and malnourished children at transplant exhibited the best growth, but remained significantly shorter and lighter even 15 years later. No effect of sex or age at transplant was noted on height or weight recovery. Post-transplant factors significantly impact growth recovery and likely caused the dichotomous growth recovery between Australian and Japanese children; 9% (9/98) of patients were overweight on body mass index calculations at 10-15 years but none were obese. Conclusions: After liver transplant, children can expect ongoing height and weight recovery for at least 10-15 years. Growth impairment at transplant and post-transplant care significantly impact long-term growth recovery. Copyright © 2013 Mosby Inc. All rights reserved.

Modern diagnosis of Epstein-Barr virus infections and post-transplant lymphoproliferative disease

Infection by Epstein-Barr virus (EBV) occurs in approximately 95% of the world s population. EBV was the first human virus implicated in oncogenesis. Characteristic for EBV primary infection are detectable IgM and IgG antibodies against viral capsid antigen (VCA). During convalescence the VCA IgM disappears while the VCA IgG persists for life. Reactivations of EBV occur both among immunocompromised and immunocompetent individuals. In serological diagnosis, measurement of avidity of VCA IgG separates primary from secondary infections. However, in serodiagnosis of mononucleosis it is quite common to encounter, paradoxically, VCA IgM together with high-avidity VCA IgG, indicating past immunity. We determined the etiology of this phenomenon and found that, among patients with cytomegalovirus (CMV) primary infection a large proportion (23%) showed antibody profiles of EBV reactivation. In contrast, EBV primary infection did not appear to induce immunoreactivation of CMV. EBV-associated post-transplant lymphoproliferative disease (PTLD) is a life threatening complication of allogeneic stem cell or solid organ transplantation. PTLD may present with a diverse spectrum of clinical symptoms and signs. Due to rapidity of PTLD progression especially after stem cell transplantation, the diagnosis must be obtained quickly. Pending timely detection, the evolution of the fatal disease may be halted by reduction of immunosuppression. A promising new PTLD treatment (also in Finland) is based on anti-CD-20 monoclonal antibodies. Diagnosis of PTLD has been demanding because of immunosuppression, blood transfusions and the latent nature of the virus. We set up in 1999 to our knowledge first in Finland for any microbial pathogen a real-time quantitative PCR (qPCR) for detection of EBV DNA in blood serum/plasma. In addition, we set up an in situ hybridisation assay for EBV RNA in tissue sections. In collaboration with a group of haematologists at Helsinki University Central Hospital we retrospectively determined the incidence of PTLD among 257 allogenic stem cell transplantations (SCT) performed during 1994-1999. Post-mortem analysis revealed 18 cases of PTLD. From a subset of PTLD cases (12/18) and a series of corresponding controls (36), consecutive samples of serum were studied by the new EBV-qPCR. All the PTLD patients were positive for EBV-DNA with progressively rising copy numbers. In most PTLD patients EBV DNA became detectable within 70 days of SCT. Of note, the appearance of EBV DNA preceded the PTLD symptoms (fever, lymphadenopathy, atypical lymphocytes). Among the SCT controls, EBV DNA occurred only sporadically, and the EBV-DNA levels remained relatively low. We concluded that EBV qPCR is a highly sensitive (100%) and specific (96%) new diagnostic approach. We also looked for and found risk factors for the development of PTLD. Together with a liver transplantation group at the Transplantation and Liver Surgery Clinic we wanted to clarify how often and how severely do EBV infections occur after liver transplantation. We studied by the EBV qPCR 1284 plasma samples obtained from 105 adult liver transplant recipients. EBV DNA was detected in 14 patients (13%) during the first 12 months. The peak viral loads of 13 asymptomatic patients were relatively low (<6600/ml), and EBV DNA subsided quickly from circulation. Fatal PTLD was diagnosed in one patient. Finally, we wanted to determine the number and clinical significance of EBV infections of various types occurring among a large, retrospective, nonselected cohort of allogenic SCT recipients. We analysed by EBV qPCR 5479 serum samples of 406 SCT recipients obtained during 1988-1999. EBV DNA was seen in 57 (14%) patients, of whom 22 (5%) showed progressively rising and ultimately high levels of EBV DNA (median 54 million /ml). Among the SCT survivors, EBV DNA was transiently detectable in 19 (5%) asymptomatic patients. Thereby, low-level EBV-DNA positivity in serum occurs relatively often after SCT and may subside without specific treatment. However, high molecular copy numbers (>50 000) are diagnostic for life-threatening EBV infection. We furthermore developed a mathematical algorithm for the prediction of development of life-threatening EBV infection.

Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.

Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits. These vascular changes may represent a previously unrecognized contributor to ongoing malaria-associated morbidity and mortality.

A qualidade de vida e a satisfação dos utentes em unidades de internamento da Rede Nacional de Cuidados Continuados Integrados (RNCCI)

RESUMO - Enquadramento: Com o aumento da Esperança Média de Vida, e o consequente envelhecimento generalizado da população portuguesa, envelhecer com boa saúde e com elevada qualidade de vida, onde as pessoas com mais de 65 anos tenham a possibilidade de expressar todas as suas potencialidades e manterem um papel ativo na sua vida e na sociedade, é vincadamente um dos maiores desafios da sociedade contemporânea. Desta forma, foi imposto à sociedade e aos sistemas de saúde, a criação de novas estratégias, que promovessem a reabilitação, a autonomia e a qualidade de vida dos idosos. Nesta linha, surgiu em Portugal a criação da Rede Nacional de Cuidados Continuados Integrados, combinando os cuidados de saúde com o apoio social adequado a esta população. Objetivos: Num primeiro objetivo, pretende-se avaliar os diferentes domínios da autoperceção de qualidade de vida de indivíduos com idade igual ou superior a 65 anos, que se encontrem em período de internamento nas diferentes tipologias de Unidades de internamento da RNCCI (Unidade de Convalescença, Unidade de Média Duração e Reabilitação e Unidade de Longa Duração e Manutenção), bem como o seu grau de (in) dependência, de risco de falha de auto-cuidado, e de risco de quedas. Como segundo objetivo propomo-nos a avaliar o grau de satisfação desses mesmos utentes, relativamente à equipa de profissionais de saúde e aos aspetos organizacionais e serviços prestados pela Unidade da RNCCI, onde se encontram internados. Por último, pretendemos averiguar a existência ou inexistência de relação entre as demais variáveis em estudo com a tipologia de Unidade de internamento onde o utente se encontra a receber cuidados. Métodos: O presente estudo é caraterizado como um estudo quantitativo, de caráter exploratório, e de índole descritivo-correlacional, que visa descrever fenómenos e, posteriormente, identificar e explorar possíveis relações entre variáveis. O estudo centrou-se em indivíduos, com idade igual ou superior a 65 anos, internados em Unidades de Cuidados Continuados da Rede Nacional de Cuidados Continuados Integrados, tendo sido efetuados dois questionários distintos: um de satisfação, e um segundo instrumento de perceção da qualidade de vida, denominado de EasyCare, estando este já cientificamente validado a nível internacional e nacional. Foi obtida uma amostra de 35 utentes.

A Classificação Internacional de Funcionalidade, Incapacidade e Saúde : um modelo multidimensional e multideterminado da funcionalidade em idosos assistidos na Rede

RESUMO: Os estudos sobre a funcionalidade da população idosa têm uma representação importante naquilo que é o atual conhecimento da demografia do mundo. Portugal posiciona-se e perspetiva-se como pertencendo aos países mais envelhecidos, possuindo uma rede de cuidados pós-agudos – a Rede Nacional de Cuidados Continuados Integrados (RNCCI)– que assiste uma parcela importante dessa população. Os aspetos conceptuais da funcionalidade de acordo com a OMS e operacionalizados pela Classificação Internacional de Funcionalidade (CIF), não mereceram até agora suficiente aplicabilidade no nosso país, inviabilizando a possibilidade de oferecermos contributos para a sua operacionalização. Da mesma forma, também os Core Sets da Classificação não têm sido sujeitos a processos de validação que contemplem amostras portuguesas, mantendo-se desconhecimento da especificidade dos fatores contextuais na nossa população. O presente estudo tem como objetivos conhecer a evolução da funcionalidade dos idosos assistidos na RNCCI na região do Algarve nas unidades de convalescença e média duração, validar o Core Set Geriátrico da OMS e propor uma versão abreviada da sua modalidade abrangente, no contexto destes cuidados. A amostra constituída por 451 idosos, dos quais 62,1% eram mulheres, revelou na pré-morbilidade níveis favoráveis de funcionalidade, com exceção para as Atividades Domésticas. Contudo, os mais idosos (≥ 85 anos), os indivíduos sem escolaridade, as mulheres e os viúvos/solteiros apresentaram mais casos desfavoráveis quando comparados com os seus pares. Na evolução da funcionalidade observámos melhorias significativas em todos os domínios avaliados, com diferenças relativamente à idade e à escolaridade; apesar dos resultados positivos os mais idosos e os indivíduos sem escolaridade apresentaram níveis inferiores de evolução. No entanto, a funcionalidade alcançada revelou ficar com resultados significativamente inferiores na comparação com aquela que os indivíduos possuíam na pré-morbilidade. Os modelos de regressão revelaram que as Funções Mentais, a Perceção do Estado de Saúde e a atividade Usar o Telefone, foram as variáveis que melhor explicaram os outcomes da funcionalidade alcançada. A validação do Core Set Geriátrico foi possível na maioria das categorias, sendo que foi no componente das Funções do Corpo onde esse processo revelou maior fragilidade. As Funções Neuromusculoesqueléticas e Relacionadas com o Movimento foram aquelas que registaram em ambos os momentos avaliativos frequências mais elevadas de deficiência, enquanto no componente Atividades & Participação isso ocorreu na atividade Utilização dos Movimentos Finos da Mão. Os capítulos Apoios e Relacionamentos e Atitudes foram considerados os Fatores Ambientais mais Facilitadores mas também com maior impacto Barreira. A proposta para o Core Set Geriátrico Abreviado resultou das categorias independentes que explicaram os modelos da funcionalidade alcançada e cujo resultado engloba um conjunto de 27 categorias, com um enfoque importante no componente Atividades/Participação de onde se destacam os domínios da Mobilidade e dos Auto Cuidados. A funcionalidade dos indivíduos e das populações deve ser considerada uma variável incontornável da Saúde Pública, cuja avaliação deve refletir uma abordagem biopsicossocial, apoiada na Classificação Internacional de Funcionalidade. A operacionalização da Classificação a partir dos Core Sets necessita de pesquisa mais aprofundada relativamente às caraterísticas psicométricas dos seus qualificadores e dos seus processos de validação.-----------ABSTRACT: The studies about the functioning of the elderly play an important role on what the present knowledge of the demography in the world is. Portugal figures high on the most aged countries, having a network of post-acute care - the National Network of Integrated Continuous Care (RNCCI) - which assists a large part of that population. The conceptual aspects of functioning according to WHO and operated by the International Classification of Functioning (ICF), have been insufficiently addressed concerning its adequate applicability in our country, hindering the contributions of its operation. In the same way, also the Core Sets of the Classification have not been subjected to validation procedures that include portuguese samples, keeping the unawareness of specificity of the contextual factors in our population. The objectives of the present study were to know the evolution of the functioning of the elderly assisted in the RNCCI in the Algarve region in units of convalescence and average duration, validate the WHO Geriatric Core Set and propose an abridged version of this comprehensive core set in this healthcare context. The sample was composed by 451 elderly people, of which 62.1% were women, they showed favourable levels in functioning in the pre-morbid state, except for Domestic Activities. However, the oldest (≥ 85 years), the individuals with no education, women and widowed/ unmarried showed more unfavourable cases when compared to their peers. In the evolution of functioning we observed significant improvements in all domains assessed, with diferences with respect to age and education. In spite of positive results, the oldest and the individuals with no education showed lower levels of evolution. However, the functioning achieved showed significantly lower results when compared to the those observed in pre-morbidity state. Regression models reveal that Mental Functions, the Perceived Health Status and the Use of the Phone activity, were the variables that better explain the functioning of the outcomes achieved. The validation of the Geriatric Core Set of ICF was possible in most categories, and Body Functions was the component where this process showed greatest weakness. Neuromusculoskeletal and Movement-Related Functions experienced in both evaluation times with higher rates of disability, while in the Activities & Participation component this occurred in the Fine Hand Use activity. The Support and Relationships and Attitudes chapters were considered the Environmental Factors most Facilitators but also with greater impact Barrier. The proposal for the Brief Geriatric Core Set has resulted from the independent categories that explained the regression models of functioning and includes a set of 27 categories, with na important emphasis on Activities & Participation component where we can highlight the areas of Mobility and Self Care domains. The functioning of individuals and populations should be considered as an unavoidable variable of Public Health, of which the assessment should reflect a biopsychosocial approach, based on the International Classification of Functioning. The operationalization of the Classification from the Core Sets requires further research regarding the psychometric characteristics of their qualifiers and their validation procedure.

L’effet des différents facteurs de croissance sur la viabilité et la prolifération des ostéoblastes scoliotiques

Résumé: La Scoliose Idiopathique de l’Adolescent (SIA) est une condition débilitante qui peut avoir comme résultat une douleur importante, une altération du fonctionnement quotidien et une détérioration de la qualité de vie. Pour les patients qui ne répondent pas au traitement conservateur, la fusion vertébrale, en utilisant des greffes osseuses, est devenue un traitement de choix pour stabiliser la colonne. Des connaissances plus pointues à propos des facteurs impliqués dans l’ostéogénèse et la formation de l’os peuvent raccourcir le processus de guérison et permettre aux patients de réintégrer leurs activités dans un laps de temps plus court. Les plaquettes peuvent jouer un rôle important dans la première étape de la guérison des fractures car elles sont une source autologue de plusieurs facteurs de croissance qui soutiennent la prolifération et la différenciation des ostéoblastes in vivo et in vitro. Au cours des dernières années, plusieurs tentatives ont été réalisées afin de trouver des traitements additionnels pour : 1) Raccourcir le temps de guérison des fractures relativement long ; 2) Obtenir une plus courte période de convalescence pour les patients qui ont besoin de prothèses ; 3) Corriger plus facilement plusieurs maladies congénitales; 4) Améliorer le processus de fusion vertébrale et 5) Développer de nouvelles approches thérapeutiques, notamment au niveau des processus régularisant le remodelage osseux et la régénération des tissus osseux. Dans le cadre de la présente étude, j’ai étudié la contribution possible du facteur de croissance de l’insuline (IGF) et du facteur vasculaire endothélial de croissance (VEGF) sur la maturation de l’ostéoblaste scoliotique dans des cultures cellulaires in vitro et j’ai comparé les résultats avec celles obtenues dans les mêmes conditions mais en stimulant les ostéoblastes avec de la mélatonine. Cette étude préliminaire a été réalisée sur des échantillons d’os récoltés de quatre patients atteints par la Scoliose Idiopathique de l‘Adolescent (SIA), ainsi que sur des échantillons d’os issus de quatre sujets témoins (cas traumatiques). Les résultats montrent que l’IGFs et le VEGFs possèdent une action d’inhibition sur la prolifération d’ostéoblastes scoliotiques et non scoliotiques, et que cette action est proportionnelle à la concentration de ces facteurs. Les ostéoblastes scoliotiques tendent à avoir une prolifération cellulaire plus rapide et plus élevée que les témoins non scoliotiques. De façon générale les ostéoblastes provenant de patients scoliotiques ont une ostéogénèse in vitro plus accélérée que le sujet non scoliotique. De plus, il semble que la mélatonine joue un rôle physiologique dans la différenciation de l’ostéoblaste scoliotique et elle semble aider à avoir une différenciation plus précoce que chez les non traités. Les ostéoblastes scoliotiques expriment un défaut d’expression de l’IGF 1 et d’IGF 1R en présence de la mélatonine. En conclusion, le VEGF A et l’IGF 1 peuvent également promouvoir la différenciation et la prolifération des ostéoblastes humains scoliotiques en culture primaire.