Dimensionality and clinical importance of pain and disability in hand osteoarthritis: Development of the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index

Objective: To develop a reliable, valid, and responsive self-administered questionnaire to probe pain, stiffness and physical disability in patients with osteoarthritis (OA) of the hand. Design: In order to assess the dimensionality of the symptomatology of hand OA, a self-administered questionnaire was developed to probe various aspects of pain (10 items), stiffness (two items), and physical function (83 items). The question inventory was generated from eight existing health status measures and an interactive process involving four rheumatologists, two physiotherapists, and an orthopaedic surgeon. Results: Face-to-face interviews were conducted with 50 OA hand patients; 39 females and 11 males with mean age 62.8 years and mean disease duration 9.4 years. Items retained were those which fulfilled specified selection criteria: prevalence greater than or equal to60% and mean importance score approximating or exceeding 2.0 Item exclusion criteria included low prevalence, gender-based, ambiguous, duplicates or similarities, alternatives, composite items, and items that were too restrictive. This process resulted in five pain, one stiffness and nine function items which have been proposed for incorporation in the AUSCAN Index. Conclusions: Using a traditional development strategy, we have constructed a self-administered multi-dimensional outcome measure for assessing hand OA. The next stage includes reliability, validity and responsiveness testing of the 15-item questionnaire. (C) 2002 OsteoArthritis Research Society Intenational. Published by Elsevier Science Ltd. All rights reserved.

A comparative study of telephone versus onsite completion of the WOMAC 3.0 Osteoarthritis Index

Objective. Outcome assessment in clinical trials using the Western Ontario and McMaster University (WOMAC 3.0) Osteoarthritis Index is traditionally achieved through self-administration of the Index. However, in other areas of clinical measurement, telephone administration has been shown to be a reliable method of acquiring data that are both accurate and complete. To address this issue in knee osteoarthritis (OA), we conducted a comparative study of telephone administration by interviewer of WOMAC LK3.0 versus onsite self-completion at the hospital. Methods. Fifty consenting patients with knee OA were randomized to complete the WOMAC LK3.0 Index by telephone interview one day, followed by onsite completion the following day, or vice versa. Neither patients nor interviewers had access to any prior scores. Results. The mean age of the 50 patients was 66.3 years (range 44-82); 34 (68%) were female and 16 (32%) male. There was excellent agreement between the mean office and telephone scores, with mean differences for the WOMAC LK3.0 pain, stiffness, and function subscale scores and total score of 0.09, 0.12, 0.78, and 0.98, respectively. These differences were well within the respective protocol defined equivalence criteria of +/- 1.7, +/- 0.9, +/- 6.4, and +/- 9.1, and represented differences from office scores of 0.9, 2.6, 2.4, and 2.2%, respectively. Conclusion. The use of telephone interviews for the WOMAC LK3.0 Index is a valid method of obtaining OA outcome measurements. These observations have important implications for designing data acquisition strategies for future OA clinical trials and for longterm observational studies.

Macrolides in cystic fibrosis. Is there a role?

A spectrum of anti-inflammatory properties, evidence of anti-infective action against Pseudomonas aeruginosa at sub-inhibitory concentrations and positive clinical experience in patients with diffuse panbronchiolitis, a disease with features in common with cystic fibrosis (CF), has prompted research to evaluate the role of macrolide therapy in patients with CF. Newer macrolides such as azithromycin have the advantage of improved tolerability and a prolonged intracellular half-life requiring an infrequent dosing regimen. Results from initial studies suggest a benefit from several months of macrolide therapy in patients with CF. An improvement in lung function was initially shown in a small open study in children, while maintenance of lung function compared with placebo, reduced acute respiratory exacerbations, and reduced systemic markers of inflammation were demonstrated in a randomized, placebo-controlled study of macrolide therapy in adult patients with CF. Additional controlled studies are required to determine optimal drug, dosage, and duration of therapy, and long-term adverse effects of prolonged therapy with macrolides in patients with CF. The potential, with long-term use, to induce resistance against other bacteria colonizing the upper respiratory tract e.g. pneumococci has not been explored. Measurement of cytokines and inflammatory mediators from the sputum of patients with CF is technically difficult and does not correlate with disease activity. There is a need for easily measurable, reproducible and clinically meaningful end-points for evaluation of new therapies in CF. The choice of appropriate outcome measures, apart from lung function, to monitor disease activity needs careful consideration in clinical trials determining the efficacy of macrolides in patients with CF. Evidence-based recommendations for the use of macrolides in the treatment of CF are not expected for some years although macrolides are already being prescribed for long-term use in some centers. There is a need for further research into mechanisms of anti-inflammatory action of macrolides in the lungs of patients with CF and whether or not such therapy may be beneficial in the long term. Copyright 2002 Adis International

Combined physiotherapy and education is efficacious for chronic low back pain

Manual therapy, exercise and education target distinct aspects of chronic low back pain and probably have distinct effects, This study aimed to determine the efficacy of a combined physiotherapy treatment that comprised all of these strategies. By concealed randomisation, 57 chronic low back pain patients were allocated to either the four-week physiotherapy program or management as directed by their general practitioners, The dependent variables of interest were pain and disability. Assessors were blind to treatment group. Outcome data from 49 subjects (86%) showed a significant treatment effect. The physiotherapy program reduced pain and disability by a mean of 1.5/10 points on a numerical rating scale (95% CI 0.7 to 2.3) and 3.9 points on the 18-point Roland Morris Disability Questionnaire (95% CI 2 to 5.8), respectively. The number needed to treat in order to gain a clinically meaningful change was 3 (95% CI 3 to 8) for pain, and 2 (95% CI 2 to 5) for disability. A treatment effect was maintained at one-year follow-up. The findings support the efficacy of combined physiotherapy treatment in producing symptomatic and functional change in moderately disabled chronic low back pain patients.

Carbamazepine augmentation for schizophrenia: How good is the evidence?

Background: Augmentation strategies in schizophrenia treatment remain an important issue because despite the introduction of several new antipsychotics, many patients remain treatment resistant. The aim of this study was to undertake a systematic review and meta-analysis of the safety and efficacy of one frequently used adjunctive compound: carbamazepine. Data sources and study selection: Randomized controlled trials comparing carbamazopine (as a sole or as an adjunctive compound) with placebo or no intervention in participants with schizophrenia or schizoaffective disorder were searched for by accessing 7 electronic databases, cross-referencing publications cited in pertinent studies, and contacting drug companies that manufacture carbamazepine. Method: The identified studies were independently inspected and their quality assessed by 2 reviewers, Because the study results were generally incompletely reported, original patient data were requested from the authors; data were received for 8 of the 10 randomized controlled trials included in the present analysis, allowing for a reanalysis of the primary data. Dichotomous variables were analyzed using the Mantel-Haenszel odds ratio and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. Results: Ten studies (total N = 283 subjects) were included. Carbamazepine was not effective in preventing relapse in the only randomized controlled trial that compared carbamazepine monotherapy with placebo. Carbamazepine tended to be less effective than perphenazine in the only trial comparing carbamazepine with an antipsychotic. Although there was a trend indicating a benefit from carbamazepine as an adjunct to antipsychotics, this trend did not reach statistical significance. Conclusion: At present, this augmentation strategy cannot be recommended for routine use. The most promising targets for future trials are patients with excitement, aggression, and schizoaffective disorder bipolar type.

Introducing OTseeker (Occupational Therapy Systematic Evaluation of Evidence): A new evidence database for occupational therapists

OTseeker (Occupational Therapy Systematic Evaluation of Evidence) is a new resource for occupational therapists that has been designed with the principle aim of increasing access to research to support clinical decisions. It contains abstracts of systematic reviews and quality ratings of randomized controlled trials (RCTs) relevant to occupational therapy. It is available, free of charge, at www.otseeker.com. This paper describes the OTseeker database and provides an example of how it may support occupational therapy practice.

Balancing the number and size of sites: An economic approach to the optimal design of cluster samples

The design of randomized controlled trials entails decisions that have economic as well as statistical implications. In particular, the choice of an individual or cluster randomization design may affect the cost of achieving the desired level of power, other things being equal. Furthermore, if cluster randomization is chosen, the researcher must decide how to balance the number of clusters, or sites, and the size of each site. This article investigates these interrelated statistical and economic issues. Its principal purpose is to elucidate the statistical and economic trade-offs to assist researchers to employ randomized controlled trials that have desired economic, as well as statistical, properties. (C) 2003 Elsevier Inc. All rights reserved.

Qualidade de vida relacionada com o exercício em indivíduos com asma: revisão sistemática

Background: A asma condiciona o dia-a-dia do indivíduo asmático do ponto de vista clínico e emocional demonstrando-se muitas vezes como um subtractivo da qualidade de vida (QV). Alguns estudos, com particular incidência nos últimos dez anos, para além de demonstrarem os benefícios da actividade física na componente clínica da doença, têm analisado o seu efeito na QV dos asmáticos. Objectivo: Analisar os efeitos da actividade física na QV de indivíduos com asma tendo por base uma revisão da literatura actual. Métodos: Foi conduzida uma pesquisa dos randomized controlled trials (RCT) compreendidos entre Janeiro de 2000 e Agosto de 2010, bem como as citações e as referências bibliográficas de cada estudo nas principais bases de dados de ciências da saúde (Academic Search Complete, DOAJ, Elsevier – Science Direct, Highwire Press, PubMed, Scielo Global, Scirus, Scopus, SpringerLink, Taylor & Francis e Wiley Interscience) com as palavras-chave: asthma, quality of life, QoL, physical activity, exercise, breathing, training e programme em todas as combinações possíveis. Os estudos foram analisados independentemente por dois revisores quanto aos critérios de inclusão e qualidade dos estudos. Resultados: Dos 1075 estudos identificados apenas onze foram incluídos. Destes, seis apresentaram um score 5/10, três 6/10 e dois 7/10 segundo a escala PEDro. Cinco destes estudos foram realizados em crianças entre os 7 e os 15 anos e os restantes em adultos. Os programas de intervenção dividiram-se em programas de treino aeróbio e programas de exercícios respiratórios. Todos programas de treino aeróbio apresentaram melhorias na QV demonstrando uma influência positiva do treino aeróbio na asma. Principais conclusões: Há uma tendência notória do benefício dos programas de treino aeróbio na QV dos indivíduos asmáticos. Os programas de exercícios respiratórios foram poucos e heterogéneos impossibilitando uma conclusão positiva quanto à sua recomendação para a melhoria da QV nesta patologia. Há uma grande necessidade de mais RCT com rigor metodológico.

A eficácia e segurança da fisioterapia respiratória no tratamento da bronquiolite aguda em crianças até 2 anos de idade: revisão sistemática

Contexto: a bronquiolite aguda é a principal patologia a afectar a criança nos primeiros 2 anos de vida, a fisioterapia respiratória é uma intervenção terapêutica utilizada com a intenção de melhorar o curso desta doença mantendo-se a incerteza sobre a sua eficácia. Objectivo: determinar a eficácia e segurança da fisioterapia respiratória em crianças com menos de 2 anos com bronquiolite aguda. Fontes de Informação: Medline (1966 a Agosto 2010), EMBASE(1990 a Agosto 2010), Pedro e Lilacs (1982 a Agosto 2010). Outra fonte de informação incluiu a bibliografia dos estudos obtidos. Selecção de estudos: estudos experimentais comparando a fisioterapia respiratória com cuidados habituais, em crianças com menos de 2 anos e bronquiolite aguda, em ventilação espontânea, em qualquer contexto. Estudos pré-experimentais ou observacionais com os mesmos participantes e intervenções foram admitidos complementarmente aos experimentais. Extracção de dados e análise: um investigador extraiu os dados dos artigos obtidos e avaliou o risco de viés. A eficácia e segurança da fisioterapia respiratória foram determinadas pelos seguintes outcomes: duração do internamento hospitalar ou do evento, variação de scores de severidade clínica, saturação periférica e suplementação de oxigénio, recidivas, recurso a antibióticos e efeitos deletérios ou deterioração clínica reportada. Síntese de dados: 6 estudos experimentais foram admitidos. As suas amostras provinham de criança internadas em hospital. As técnicas de fisioterapia respiratória foram comparadas com cuidados habituais. Nenhum estudo evidenciou melhoria dos outcomes de interesse na comparação entre grupos, excepto avaliações de curta duração da saturação periférica de oxigénio e scores de severidade clínica. 1 estudo reportou uma percentagem significativamente maior no grupo submetido a fisioterapia respiratória de crianças que vomitaram, tiveram uma desestabilização respiratória transitória, e na percepção de stress da criança pelos cuidadores. São relatadas ainda fracturas costais a causa de fisioterapia respiratória. Limitações: o risco de viés era alto em 2 estudos, baixo num estudo e indeterminado nos restantes. Conclusões: aparentemente a fisioterapia respiratória não é eficaz e pode produzir efeitos deletérios importantes, mas a evidência é pobre, carecendo de novos estudos.

Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial

OBJECTIVE: To compare the reactogenicity of three yellow fever (YF) vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo. METHODS: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered ("day 0") following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests. RESULTS: Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.

Familial amyloid polyneuropathy (FAP): clinical features, pathophysiology and treatment

In the literature, concepts of “polyneuropathy”, “peripheral neuropathy” and “neuropathy” are often mistakenly used as synonyms. Polyneuropathy is a specific term that refers to a relatively homogenous process that affects multiple peripheral nerves. Most of these tend to present as symmetric polyneuropathies that first manifest in the distal portions of the affected nerves. Many of these distal symmetric polyneuropathies are due to toxic-metabolic causes such as alcohol abuse and diabetes mellitus. Other distal symmetric polyneuropathies may result from an overproduction of substances that result in nerve pathology such as is observed in anti-MAG neuropathy and monoclonal gammopathy of undetermined significance. Other “overproduction” disorders are hereditary such as noted in the Portuguese type of familial amyloid polyneuropathy (FAP). FAP is a manifestation of a group of hereditary amyloidoses; an autosomal dominant, multisystemic disorder wherein the mutant amyloid precursor, transthyretin, is produced in excess primarily by the liver. The liver accounts for approximately 98% of all transthyretin production. FAP is confirmed by detecting a transthyretin variant with a methionine for valine substitution at position 30 [TTR (Met30)]. Familial Amyloidotic Polyneuropathy (FAP) – Portuguese type was first described by a Portuguese neurologist, Corino de Andrade in 1939 and published in 1951. Most persons with this disorder are descended from Portuguese sailors who sired offspring in various locations, primarily in Sweden, Japan and Mallorca. Their descendants emigrated worldwide such that this disorder has been reported in other countries as well. More than 2000 symptomatic cases have been reported in Portugal. FAP progresses rapidly with an average time course from symptom onset to multi-organ involvement and death between ten and twenty years. Treatments directed at removing this aberrant protein such as plasmapheresis and immunoadsorption proved to be unsuccessful. Liver transplantation has been the only effective solution as evidenced by almost 2000 liver transplants performed worldwide. A therapy for FAP with a novel agent, “Tafamidis” has shown some promise in ongoing phase III clinical trials. It is well recognized that regular physical activity of moderate intensity has a positive effect on physical fitness as gauged by body composition, aerobic capacity, muscular strength and endurance and flexibility. Physical fitness has been reported to result in the reduction of symptoms and lesser impairment when performing activities of daily living. Exercise has been advocated as part of a comprehensive approach to the treatment of chronic diseases. Therefore, this chapter concludes with a discussion of the role of exercise training on FAP.

Effectiveness of motivational interviewing at improving oral health: a systematic review

OBJECTIVE : To analyze the effectiveness of motivational interviewing (MI) at improving oral health behaviors (oral hygiene habits, sugar consumption, dental services utilization or use of fluoride) and dental clinical outcomes (dental plaque, dental caries and periodontal status). METHODS : A systematic search of PubMed, LILACS, SciELO, PsyINFO, Cochrane and Google Scholar bibliographic databases was conducted looking for intervention studies that investigated MI as the main approach to improving the oral health outcomes investigated. RESULTS : Of the 78 articles found, ten met the inclusion criteria, all based on randomized controlled trials. Most studies (n = 8) assessed multiple outcomes. Five interventions assessed the impact of MI on oral health behaviors and nine on clinical outcomes (three on dental caries, six on dental plaque, four on gingivitis and three on periodontal pockets). Better quality of evidence was provided by studies that investigated dental caries, which also had the largest population samples. The evidence of the effect of MI on improving oral health outcomes is conflicting. Four studies reported positive effects of MI on oral health outcomes whereas another four showed null effect. In two interventions, the actual difference between groups was not reported or able to be recalculated. CONCLUSIONS : We found inconclusive effectiveness for most oral health outcomes. We need more and better designed and reported interventions to fully assess the impact of MI on oral health and understand the appropriate dosage for the counseling interventions.

Non-adherence to telemedicine interventions for drug users: systematic review

OBJECTIVE To estimate rates of non-adherence to telemedicine strategies aimed at treating drug addiction. METHODS A systematic review was conducted of randomized controlled trials investigating different telemedicine treatment methods for drug addiction. The following databases were consulted between May 18, 2012 and June 21, 2012: PubMed, PsycINFO, SciELO, Wiley (The Cochrane Library), Embase, Clinical trials and Google Scholar. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of the studies. The criteria evaluated were: appropriate sequence of data generation, allocation concealment, blinding, description of losses and exclusions and analysis by intention to treat. There were 274 studies selected, of which 20 were analyzed. RESULTS Non-adherence rates varied between 15.0% and 70.0%. The interventions evaluated were of at least three months duration and, although they all used telemedicine as support, treatment methods differed. Regarding the quality of the studies, the values also varied from very poor to high quality. High quality studies showed better adherence rates, as did those using more than one technique of intervention and a limited treatment time. Mono-user studies showed better adherence rates than poly-user studies. CONCLUSIONS Rates of non-adherence to treatment involving telemedicine on the part of users of psycho-active substances differed considerably, depending on the country, the intervention method, follow-up time and substances used. Using more than one technique of intervention, short duration of treatment and the type of substance used by patients appear to facilitate adherence.

Downstream processing development of enveloped viruses for clinical applications: innovative tools for rational process optimization

Dissertation presented to obtain a Ph.D. degree in Engineering and Technology Sciences, Biotechnology at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa