RESUMO
OBJECTIVES: To determine the efficacy of community water-based therapy for the management of lower limb osteoarthritis (OA) in older patients. DESIGN: A pre-experimental matched-control study was used to estimate efficacy of water-based exercise treatment, to check design assumptions and delivery processes. The main study was a randomised controlled trial of the effectiveness of water-based exercise (treatment) compared with usual care (control) in older patients with hip and/or knee OA. The latter was accompanied by an economic evaluation comparing societal costs and consequences of the two treatments. SETTING: Water exercise was delivered in public swimming pools in the UK. Physical function assessments were carried out in established laboratory settings. PARTICIPANTS: 106 patients (93 women, 13 men) over the age of 60 years with confirmed hip and/or knee OA took part in the preliminary study. A similar, but larger, group of 312 patients (196 women, 116 men) took part in the main study, randomised into control (159) and water exercise (153) groups. INTERVENTIONS: Control group patients received usual care with quarterly semi-structured telephone interview follow-up only. The intervention in the main study lasted for 1 year, with a further follow-up period of 6 months. MAIN OUTCOME MEASURES: Pain score on the Western Ontario and McMaster Universities OA index (WOMAC). Additional outcome measures were included to evaluate effects on quality of life, cost-effectiveness and physical function measurements. RESULTS: Short-term efficacy of water exercise in the management of lower limb OA was confirmed, with effect sizes ranging from 0.44 [95% confidence interval (CI) 0.03 to 0.85] on WOMAC pain to 0.76 (95% CI 0.33 to 1.17) on WOMAC physical function. Of 153 patients randomised to treatment, 82 (53.5%) were estimated to have complied satisfactorily with their treatment at the 1-year point. This had declined to 28 (18%) by the end of the 6-month follow-up period, during which support for the intervention had been removed and those wishing to continue exercise had to pay their own costs for maintaining their exercise treatment. High levels of co-morbidity were recorded in both groups. Nearly two thirds of all patients had a significant other illness in addition to their OA. Fifty-four control and 53 exercise patients had hospital inpatient episodes during the study period. Water exercise remained effective in the main study but overall effect size was small, on WOMAC pain at 1 year, a reduction of about 10% in group mean pain score. This had declined, and was non-significant, at 18 months. Mean cost difference estimates showed a saving in the water exercise group of pound123--175 per patient per annum and incremental cost-effectiveness ratios ranged from pound3838 to pound5951 per quality-adjusted life-year (QALY). Net reduction in pain was achieved at a net saving of pound135--175 per patient per annum and the ceiling valuation of pound580--740 per unit of WOMAC pain reduction was favourably low. CONCLUSIONS: Group-based exercise in water over 1 year can produce significant reduction in pain and improvement in physical function in older adults with lower limb OA, and may be a useful adjunct in the management of hip and/or knee OA. The water-exercise programme produced a favourable cost--benefit outcome, using reduction in WOMAC pain as the measure of benefit. Further research is suggested into other similar public health interventions. Investigation is also needed into how general practice can best be supported to facilitate access to participants for research trials in healthcare, as well as an examination of the infrastructure and workforce capacities for physical activity delivery and the potential extent to which healthcare may be supported in this way. More detailed research is required to develop a better understanding of the types of exercise that will work for the different biomechanical subtypes of knee and hip OA and investigation is needed on access and environmental issues for physical activity programmes for older people, from both a provider and a participant perspective, the societal costs of the different approaches to the management of OA and longer term trends in outcome measures (costs and effects).
Assuntos
Terapia por Exercício , Osteoartrite do Quadril/economia , Osteoartrite do Quadril/terapia , Osteoartrite do Joelho/economia , Osteoartrite do Joelho/terapia , Piscinas , Idoso , Serviços de Saúde Comunitária , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Projetos PilotoRESUMO
Traditional treatment strategies and public health interventions aimed at reducing the incidence of obesity are proving inadequate at controlling the global epidemic of this condition. The main focus of any intervention should be on preventing small excesses of weight, which lead to large weight gain over time, as once a large amount of excess weight is gained, it is very difficult to lose. The only effective approach is for governments to implement radical policy change, to regulate food consumption and control the food industry in a similar way to that of the tobacco industry, by banning the advertising of selected produce, taxing certain foods, and rationing the purchase of others.
Assuntos
Surtos de Doenças/prevenção & controle , Obesidade/epidemiologia , Publicidade/legislação & jurisprudência , Ingestão de Energia/fisiologia , Alimentos/economia , Indústria Alimentícia/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Humanos , Estilo de Vida , Obesidade/prevenção & controle , Prevalência , Saúde Pública , Impostos/economia , Aumento de Peso/fisiologiaRESUMO
OBJECTIVE: To examine the effectiveness of a 12-month community-based water exercise programme on measures of self-reported health and physical function in people aged over 60 years old with knee-hip osteoarthritis (OA). DESIGN: A quasi-experimental design consisting of an exercise group and an age-matched control group. SETTING: Public community swimming pool in Sheffield, UK. SUBJECTS: One hundred and six community-dwelling sedentary older people, with confirmed knee-hip osteoarthritis, enrolled in an experimental controlled trial for 12 months. Sixty-six subjects in the exercise group were offered a water-exercise programme. Forty age-matched, nonexercising, 'control' subjects received monthly education material and quarterly telephone calls. INTERVENTIONS: Participants in the exercise group were asked to attend two exercise sessions a week of 1 hour duration led by specially trained swimming instructors. MAIN MEASURES: Primary outcome measure was the disease-specific Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Secondary outcomes included a battery of performance-based physical function tests. RESULTS: Adherence to exercise averaged 70% (+/- 14%) over the year: 77% of the exercising subjects and 89% control subjects completed both pre- and post-outcome measures. After one year, participants in the exercise group experienced a significant improvement in physical function (4.0 +/- 9.1 versus -0.4 +/- 7.3 units; 95% confidence interval (CI) 0.96-7.96, p < 0.05) and reduction in the perception of pain (1.3 +/- 3.7 versus 0.2 +/- 2.5 units; 95% CI -0.19-2.52, p < 0.05) compared with the control group, as measured by the WOMAC Osteoarthritis Index. In addition, the exercise group performed significantly better in the ascending and descending stairs tests (p < 0.05), had significantly greater improvements in knee range of movement (p < 0.01) and hip range of movements (p < 0.005). There were no significant differences in the two groups for quadriceps muscle strength and psychosocial well-being (Arthritis Impact Measurement Scales 2 questionnaire). CONCLUSIONS: Older people with knee/hip osteoarthritis gained modest improvements in measures of physical function, pain, general mobility and flexibility after participating in 12 months of community-based water exercise.
Assuntos
Terapia por Exercício , Osteoartrite do Quadril/reabilitação , Osteoartrite do Joelho/reabilitação , Idoso , Serviços de Saúde Comunitária , Feminino , Humanos , Masculino , Cooperação do PacienteRESUMO
This study reports the results of a battery of physical function tests used to assess physical function of older patients with clinical knee and/or hip osteoarthritis (OA), and the correlation to the WOMAC Index (disease-specific questionnaire). A total of 106 sedentary subjects, aged >60 years (mean 69.4, S.D. 5.9) with hip and/or knee OA (mean 12.2 yrs, S.D. 11.0) participated in the study. Mobility, joint flexibility and muscle strength were evaluated by recording time to: walk a distance of 8', ascend/descend 4 stairs, rise from/sit down from a chair (5 times). Hip/knee flexion and isometric quadriceps strength were also measured. Categories of performance were formed by dividing data into quartiles for each test (1=highest, 4=lowest score, 5=unable to complete) and, by summing the category scores, a total summary score (TSS) was obtained. The battery of physical function tests showed an acceptable test-retest reliability (ICC of all tasks > or =0.80) and internal consistency (Cronbach's alpha > or =0.80). Performance scores on walking, stair climb, chair-rise and ROM of affected OA joints were significantly correlated with each other, and with the WOMAC Index (P<0.05, Spearman's correlation). Lower scores on the TSS were associated with lower scores on all the WOMAC Index items (P<0.001). This study shows that a simple battery of physical function tests in combination with the WOMAC Index are reliable and may be useful outcome measures in the evaluation of therapeutic interventions and geriatric rehabilitation.
Assuntos
Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Coortes , Inglaterra , Feminino , Nível de Saúde , Humanos , Masculino , Contração Muscular , Músculo Esquelético/fisiopatologia , Medição da Dor/normas , Qualidade de Vida , Amplitude de Movimento Articular , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Inquéritos e Questionários , CaminhadaRESUMO
In a feline model of mucopolysaccharidosis type VI (MPS VI), recombinant feline N-acetylgalactosamine-4-sulfatase (rf4S) administered at a dose of 1 mg/kg of body weight, altered the clinical course of the disease in two affected cats treated from birth. After 170 days of therapy, both cats were physically indistinguishable from normal cats with the exception of mild corneal clouding. Feline N-acetylgalactosamine-4-sulfatase was effective in reducing urinary glycosaminoglycan levels and lysosomal storage in all cell types examined except for corneal keratocytes and cartilage chondrocytes. In addition, skeletal pathology was nearly normalized as assessed by radiographic evidence and bone morphometric analysis. Comparison of results with a previous study in which recombinant human 4S (rh4S) was used at an equivalent dose and one 5 times higher indicated that rf4S had a more pronounced effect on reducing pathology than the same dose of rh4S, and in some instances such as bone pathology and lysosomal storage in aorta smooth muscle cells, it was as good as, or better than, the higher dose of rh4S. We conclude that in the feline MPS VI model the use of native or same species enzyme for enzyme replacement therapy has significant benefits.
Assuntos
Mucopolissacaridose VI/tratamento farmacológico , N-Acetilgalactosamina-4-Sulfatase/administração & dosagem , Animais , Gatos , Humanos , N-Acetilgalactosamina-4-Sulfatase/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Especificidade da EspécieRESUMO
Lysosomes degrade a wide range of macromolecules to yield monomer products which are exported out of the lysosome by a series of transporters. In addition, lysosomes perform a range of other functions which are cell or tissue specific. In order to gain insight into the tissue specific role of lysosomes, carrier-ampholyte two-dimensional electrophoresis (2-DE) was used in combination with N-terminal sequencing to identify the major proteins present in both the membrane and luminal space of placental lysosomes. From the 45 N-terminal peptide sequences generated, 14 luminal and five membrane proteins were identified while three other sequences were novel. The sequenced proteins were a mixture of lysosomal and non-lysosomal proteins. The lysosomal proteins consisted of gamma-interferon-inducible protein (IP-30), Saposin D, cathepsins B and D, beta-hexosaminidase, palmitoyl protein thioesterase, alpha-glucosidase, and LAMP-1. The non-lysosomal proteins were serum albumin, serotransferrin, haemoglobin gamma G chain, alpha-1-antitrypsin, placental lactogen, endoplasmin, peptide binding protein 74, p60 lymphocyte protein, p450 side chain cleavage enzyme and placental alkaline phosphatase. The 2-DE maps obtained in this study are the first to identify the major proteins in both the lumen and membrane of placental lysosomes through sequence analysis, and thus provide the basis upon which to build a complete 2-DE database of the lysosome. Furthermore, the identities of the proteins sequenced from the placental lysosomes suggest a role for lysosomes in the transport of nutrients across the trophoblastic layer.
Assuntos
Lisossomos/química , Proteínas de Membrana/análise , Placenta/metabolismo , Proteínas da Gravidez/análise , Gravidez/metabolismo , Adulto , Sequência de Aminoácidos , Fracionamento Celular , Eletroforese em Gel Bidimensional , Feminino , Humanos , Membranas Intracelulares/química , Dados de Sequência Molecular , Mapeamento de PeptídeosRESUMO
Early diagnosis of lysosomal storage disorders (LSDs), before the onset of irreversible pathologies, will be a key factor in the development of effective therapies for many of these disorders. Newborn screening offers a potential mechanism for the early detection of these disorders. From studies of both normal and LSD-affected human skin fibroblasts we identified the lysosome-associated membrane protein LAMP-1 as a potential diagnostic marker. We have developed a sensitive method for the quantification of this protein with a time-resolved fluorescence immunoassay. A soluble form of LAMP-1 was observed in plasma samples, and determination of 152 unaffected individuals gave a median value of 303 micrograms/L with the 5th and 95th percentile at 175 and 448 micrograms/L respectively. Plasma samples from 320 LSD-affected individuals representing 25 different disorders were assayed. We observed that 17 of the 25 disorder groups tested had > 88% of individuals above the 95th percentile of the control population, with 12 groups having 100% above the 95th percentile. Overall, 72% of patients had LAMP-1 concentrations above the 95th percentile of the unpartitioned control population. We suggest that LAMP-1 may be a useful marker in newborn screening for LSDs.
Assuntos
Antígenos CD/sangue , Doenças por Armazenamento dos Lisossomos/diagnóstico , Glicoproteínas de Membrana/sangue , Adolescente , Adulto , Idoso , Antígenos CD/análise , Biomarcadores/sangue , Criança , Pré-Escolar , Fibroblastos , Fluorimunoensaio , Humanos , Lactente , Recém-Nascido , Proteínas de Membrana Lisossomal , Lisossomos/química , Lisossomos/enzimologia , Glicoproteínas de Membrana/análise , Microscopia Eletrônica , Pessoa de Meia-IdadeRESUMO
We report evidence of a dose responsive effect of enzyme replacement therapy in mucopolysaccharidosis type VI cats from birth, at the clinical, biochemical, and histopathological level. Cats treated with weekly, intravenous recombinant human N-acetylgalactosamine-4-sulfatase at 1 and 5 mg/kg, were heavier, more flexible, had greatly reduced or no spinal cord compression, and had almost normal urinary glycosaminoglycan levels. There was near normalization or complete reversal of lysosomal storage in heart valve, aorta, skin, dura, liver, and brain perivascular cells. No reduction in lysosomal vacuolation was observed in cartilage or cornea; however, articular cartilage was thinner and external ear pinnae were larger in some treated cats. Degenerative joint changes were not obviously delayed in treated cats. Skeletal pathology was reduced, with more normalized bone dimensions and with more uniform bone density and trabecular pattern clearly visible on radiographs by 5 to 6 mo; however, differences between 1 and 5 mg/kg dose rates were not clearly distinguishable. At a dose of 0.2 mg/kg, disease was not significantly altered in the majority of parameters examined. Lysosomal storage was present in all tissues examined in the midterm mucopolysaccharidosis type VI fetus and increased rapidly in extent and severity from birth.