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2.
BMJ Open ; 4(4): e004473, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24736035

RESUMO

OBJECTIVE: To evaluate the process of implementation of the modified London Stroke Carers Training Course (LSCTC) in the Training Caregivers After Stroke (TRACS) cluster randomised trial and contribute to the interpretation of the TRACS trial results. The LSCTC was a structured competency-based training programme designed to help develop the knowledge and skills (eg, patient handling or transfer skills) essential for the day-to-day management of disabled survivors of stroke. The LSCTC comprised 14 components, 6 were mandatory (and delivered to all) and 8 non-mandatory, to be delivered based on individual assessment of caregiver need. DESIGN: Process evaluation using non-participant observation, documentary analysis and semistructured interviews. PARTICIPANTS: Patients with stroke (n=38), caregivers (n=38), stroke unit staff (n=53). SETTINGS: 10 of the 36 stroke units participating in the TRACS trial in four English regions (Yorkshire, North West, South East and South West, Peninsula). RESULTS: Preparatory cascade training on delivery of the LSCTC did not reach all staff and did not lead to multidisciplinary team (MDT) wide understanding of, engagement with or commitment to the LSCTC. Although senior therapists in most intervention units observed developed ownership of the LSCTC, MDT working led to separation rather than integration of delivery of LSCTC elements. Organisational features of stroke units and professionals' patient-focused practices limited the involvement of caregivers. Caregivers were often invited to observe therapy or care being provided by professionals but had few opportunities to make sense of, or to develop knowledge and stroke-specific skills provided by the LSCTC. Where provided, caregiver training came very late in the inpatient stay. Assessment and development of caregiver competence was not commonly observed. CONCLUSIONS: Contextual factors including service improvement pressures and staff perceptions of the necessity for and work required in caregiver training impacted negatively on implementation of the caregiver training intervention. Structured caregiver training programmes such as the LSCTC are unlikely to be practical in settings with short inpatient stays. Stroke units where early supported discharge is in place potentially offer a more effective vehicle for introducing competency based caregiver training. LINKED TRACS CLUSTER RANDOMISED CONTROLLED TRIAL NUMBER: ISRCTN49208824.


Assuntos
Cuidadores/educação , Avaliação de Processos em Cuidados de Saúde , Reabilitação do Acidente Vascular Cerebral , Atividades Cotidianas , Idoso , Inglaterra , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Qualidade de Vida
3.
Horm Cancer ; 4(5): 270-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23715671

RESUMO

Lung cancer is the leading cause of cancer death worldwide. Sex differences in lung cancer incidence and survival are known. Female sex is an independent good prognostic factor. Estrogens appear to play a key role in lung cancer outcomes. Accordingly, antiestrogen use may also influence survival in female non-small cell lung cancer (NSCLC) patients. In this study, we compared survival among antiestrogen users and nonusers. We performed a retrospective population-based study. Using the Manitoba Cancer Registry (MCR), we identified all women diagnosed with NSCLC from 2000 to 2007. The population-based Drug Program Information Network was accessed to establish which patients received antiestrogens. Demographic data (e.g., smoking patterns, stage, histology) were gathered from the MCR and by chart review. Survival differences between antiestrogen-exposed and not exposed groups were compared using multivariable Cox regression. Two thousand three hundred twenty women fit our patient criteria, of which 156 had received antiestrogens. Exposure to antiestrogens was associated with a significantly decreased mortality in those exposed both before and after the diagnosis of NSCLC (adjusted hazard ratio, 0.42, p = 0.0006). This association remained consistent across age and stage groups. Antiestrogen use before and after the diagnosis of NSCLC is associated with decreased mortality. This supports previous evidence that estrogens may play a key role in the biology and outcomes of NSCLC and suggests a potential therapeutic use for these agents in this disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Moduladores de Receptor Estrogênico/administração & dosagem , Neoplasias Pulmonares/mortalidade , Idoso , Idoso de 80 Anos ou mais , Canadá , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Manitoba/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do Tratamento
4.
Appl Radiat Isot ; 70(7): 1228-37, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22245364

RESUMO

The steadily increasing number of explosive threat classes, including home-made explosives (HMEs), liquids, amorphous and gels (LAGs), is forcing up the false-alarm rates of security screening equipment. This development can best be countered by increasing the number of features available for classification. X-ray diffraction intrinsically offers multiple features for both solid and LAGs explosive detection, and is thus becoming increasingly important for false-alarm and cost reduction in both carry-on and checked baggage security screening. Following a brief introduction to X-ray diffraction imaging (XDI), which synthesizes in a single modality the image-forming and material-analysis capabilities of X-rays, the Multiple Inverse Fan Beam (MIFB) XDI topology is described. Physical relationships obtaining in such MIFB XDI components as the radiation source, collimators and room-temperature detectors are presented with experimental performances that have been achieved. Representative X-ray diffraction profiles of threat substances measured with a laboratory MIFB XDI system are displayed. The performance of Next-Generation (MIFB) XDI relative to that of the 2nd Generation XRD 3500TM screener (Morpho Detection Germany GmbH) is assessed. The potential of MIFB XDI, both for reducing the exorbitant cost of false alarms in hold baggage screening (HBS), as well as for combining "in situ" liquid and solid explosive detection in carry-on luggage screening is outlined.

5.
Fam Pract ; 29(2): 203-12, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21982810

RESUMO

BACKGROUND: Chronic musculoskeletal pain (CMP) is treated in primary care by a wide range of health professionals including chiropractors, osteopaths and physiotherapists. AIMS: To explore patients and chiropractors, osteopaths and physiotherapists' beliefs about CMP and its treatment and how these beliefs influenced care seeking and ultimately the process of care. METHODS: Depth interviews with a purposive sample of 13 CMP patients and 19 primary care health professionals (5 osteopaths, 4 chiropractors and 10 physiotherapists). RESULTS: Patients' models of their CMP evolved throughout the course of their condition. Health professionals' models also evolved throughout the course of their treatment of patients. A key influence on patients' consulting behaviour appeared to be finding someone who would legitimate their suffering and their condition. Health professionals also recognized patients' need for legitimation but often found that attempts to explore psychological factors, which may be influencing their pain could be construed by patients as delegitimizing. Patients developed and tailored their consultation strategies throughout their illness career but not always in a strategic fashion. Health professionals also reflected on how patients' developing knowledge and changing beliefs altered their expectations. Therefore, overall within our analysis, we identified three themes: 'the evolving nature of patients and health professionals models of understanding CMP'; 'legitimating suffering' and 'development and tailoring of consultation and treatment strategies throughout patients' illness careers'. CONCLUSIONS: Seeking care for any condition is not static but a process particularly for long-term conditions such as CMP. This may need to be taken into account by both CMP patients and their treating health professionals, in that both should not assume that their views about causation and treatment are static and that instead they should be revisited on a regular basis. Adopting a shared decision-making approach to treatment may be useful particularly for long-term conditions; however, in some cases, this may be easier said than done due to both patients' and health professionals' sometimes discomfort with adopting such an approach. Training and support for both health professionals and patients may be helpful in facilitating a shared decision-making approach.


Assuntos
Quiroprática , Tomada de Decisões , Dor Musculoesquelética/terapia , Médicos Osteopáticos , Fisioterapeutas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/psicologia
6.
Aliment Pharmacol Ther ; 32(4): 591-602, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20528826

RESUMO

BACKGROUND: Current questionnaires for assessing gastro-oesophageal reflux disease (GERD) symptoms are limited in their ability to capture nocturnal symptoms. AIM: To develop and validate an instrument, the Nocturnal Gastro-oesophageal Reflux Disease Symptom Severity and Impact Questionnaire (N-GSSIQ), to assess severity and impact of nocturnal GERD symptoms. METHODS: Two focus groups and 16 cognitive debriefing interviews were conducted among GERD patients to identify key issues about nocturnal symptoms. A draft instrument was tested in 196 patients at 11 clinics in the US to evaluate psychometric properties. Exploratory factor and item response theory analyses were conducted to finalize items and subscales. Internal consistency reliability, reproducibility and construct validity were examined. RESULTS: Mean age was 45 (s.d. = 13.8) years; 76% were female and 68% were Caucasian. Patient-rated severity was mild-moderate for 69% of participants; 48% reported symptoms on two to three nights the past week. The final questionnaire includes 20 items and three subscales: Nocturnal GERD Symptoms, Morning Impact of Nocturnal GERD and Concern about Nocturnal GERD. The subscales demonstrated internal consistency reliability (Cronbach's alpha 0.84-0.94) and were significantly correlated with similar measures and disease severity (0.41-0.81; P < 0.0001). CONCLUSION: The results support the reliability and validity of the N-GSSIQ as a measure of severity, morning impact and concern about nocturnal GERD.


Assuntos
Refluxo Gastroesofágico/psicologia , Transtornos do Sono-Vigília/psicologia , Inquéritos e Questionários/normas , Adulto , Idoso , Ritmo Circadiano , Análise Fatorial , Feminino , Grupos Focais , Refluxo Gastroesofágico/diagnóstico , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia
7.
Appl Radiat Isot ; 68(6): 993-1005, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20138773

RESUMO

This review discusses the principles and technological realisation of a technique, termed Compton scatter imaging (CSI), which is based on spatially resolved detection of Compton scattered X-rays. The applicational focus of this review is to objects of historical interest. Following a historical survey of CSI, a description is given of the major characteristics of Compton X-ray scatter. In particular back-scattered X-rays allow massive objects to be imaged, which would otherwise be too absorbing for the conventional transmission X-ray technique. The ComScan (an acronym for Compton scatter scanner) is a commercially available backscatter imaging system, which is discussed here in some detail. ComScan images from some artefacts of historical interest, namely a fresco, an Egyptian mummy and a mediaeval clasp are presented and their use in historical analysis is indicated. The utility of scientific and technical advance for not only exploring history, but also restoring it, is briefly discussed.


Assuntos
Diagnóstico por Imagem/métodos , Espalhamento de Radiação , Raios X , Diagnóstico por Imagem/instrumentação , História Medieval , Humanos , Múmias/diagnóstico por imagem , Radiografia
8.
Appl Ergon ; 41(4): 504-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18930180

RESUMO

Photosensitive epilepsy came to prominence in the 1950s with the advent of television. Photosensitive epilepsy occurs in 1 in 4000 of the population. The incidence is 1.1 per 100,000 per annum, however amongst 7-19 year-olds the incidence is more than five times as common. Photosensitive epilepsy is twice as common in females as in males. The onset is around puberty, but less than 25 per cent of patients lose their photosensitivity in their twenties. Patients are investigated in the EEG laboratory using intermittent photic stimulation. Peak sensitivity is between 16 and 20 flashes/s but 49 per cent of patients are sensitive to 50 flashes/s, explaining the sensitivity to PAL television systems. From 1993 the development of broadcast guidelines was developed restricting both flash rates and the areas of screen involved, as well as the use of long-wavelength red. Automatic analysis systems can now test material for compliance with guidelines in real time.


Assuntos
Epilepsia Reflexa , Estimulação Luminosa/efeitos adversos , Convulsões/etiologia , Adolescente , Criança , Epilepsia Reflexa/epidemiologia , Feminino , Humanos , Masculino , Medição de Risco , Televisão/legislação & jurisprudência , Reino Unido/epidemiologia , Jogos de Vídeo/legislação & jurisprudência , Adulto Jovem
9.
Eur Respir J ; 34(3): 648-54, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19720809

RESUMO

There is need for a validated short, simple instrument to quantify chronic obstructive pulmonary disease (COPD) impact in routine practice to aid health status assessment and communication between patient and physician. Current health-related quality of life questionnaires provide valid assessment of COPD, but are complex, which limits routine use. The aim of the present study was to develop a short validated patient-completed questionnaire, the COPD Assessment Test (CAT), assessing the impact of COPD on health status. 21 candidate items identified through qualitative research with COPD patients were used in three prospective international studies (Europe and the USA, n = 1,503). Psychometric and Rasch analyses identified eight items fitting a unidimensional model to form the CAT. Items were tested for differential functioning between countries. Internal consistency was excellent: Cronbach's alpha = 0.88. Test re-test in stable patients (n = 53) was very good (intra-class correlation coefficient 0.8). In the sample from the USA, the correlation with the COPD-specific version of the St George's Respiratory Questionnaire was r = 0.80. The difference between stable (n = 229) and exacerbation patients (n = 67) was five units of the 40-point scale (12%; p<0.0001). The CAT is a short, simple questionnaire for assessing and monitoring COPD. It has good measurement properties, is sensitive to differences in state and should provide a valid, reliable and standardised measure of COPD health status with worldwide relevance.


Assuntos
Indicadores Básicos de Saúde , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Psicometria , Doença Pulmonar Obstrutiva Crônica/psicologia , Qualidade de Vida , Reprodutibilidade dos Testes , Estados Unidos
10.
Neurology ; 72(18): 1595-600, 2009 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-19414727

RESUMO

BACKGROUND: Determination of auditory function is a fundamental part of a complete neurologic examination. Disability from permanent hearing loss is common in the general population. Current bedside auditory tests are unreliable and cumbersome. We evaluated the calibrated finger rub auditory screening test (CALFRAST) as a routine diagnostic tool. METHODS: The sound spectrum and mean peak intensities of standard finger rub were measured, as well as background noise. CALFRAST overlapped the frequency spectrum of normal speech. Patients and companions were recruited from a neurology clinic. With arms extended, two stimulus intensities were presented: strong finger rub (CALFRAST-Strong 70) and the faintest rub that the examiner could hear (CALFRAST-Faint 70). With subjects' eyes closed, each ear's CALFRAST threshold was ascertained and then compared with its audiometric measure. The normal threshold was considered to be 25 dB. Validity, reliability, and discrimination abilities were obtained using standard methods. RESULTS: Two hundred twenty-one subjects (442 ears; 58% women) were examined. Ages ranged from 18 to 88 years, with a mean of 46 years. Eighty-five subjects (39%) had some degree of hearing loss. Both specificity and positive predictive value of CALFRAST-Strong 70 were 100%. Both sensitivity and negative predictive value of CALFRAST-Faint 70 were 99%, with a negative likelihood ratio <0.1. Area under the receiver operating characteristic curve was 0.94, consistent with excellent discrimination ability. Both intrarater and interrater reliability were excellent, both kappa >0.8. Subjects' self-assessment of hearing was unreliable. CONCLUSION: The calibrated finger rub auditory screening test (CALFRAST) is simple, accurate, inexpensive, and reliable. As a routine screening tool, CALFRAST may contribute to more efficient identification of auditory impairment.


Assuntos
Estimulação Acústica/métodos , Audiometria/métodos , Dedos/fisiologia , Transtornos da Audição/diagnóstico , Programas de Rastreamento/métodos , Sistemas Automatizados de Assistência Junto ao Leito/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Audiometria/economia , Análise Custo-Benefício , Feminino , Transtornos da Audição/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Discriminação da Altura Tonal/fisiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
11.
Appl Radiat Isot ; 67(2): 287-95, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18805014

RESUMO

A brief description is given of some applications of X-ray diffraction imaging (XDI) in security screening, including detection of narcotics and a wide range of explosives: organic (plastic) explosives, liquids, home-made explosives (HMEs) and special nuclear materials (SNMs). A Bayesian formulation of the "rare event scenario" is presented, allowing the probability to be quantified that an unlikely threat is indeed present when an uncertain detection system raises an alarm. Granted the utility of X-ray diffraction (XRD) as a significant screening modality for false-alarm resolution, the topic of its technological feasibility is addressed. It is shown that, in analogy to computed tomography, XDI permits a significant reduction to be achieved in measurement time per object volume element (voxel) compared with that of a classical X-ray diffractometer. This reduction can be accomplished by designing the XDI system to record energy-dispersive XRD profiles from many volume elements (object voxels) in parallel. A general scheme for designing "massively-parallel" (MP) XDI systems is presented. XDI configurations of the first generation (1 voxels(-1)), second generation (100 voxelss(-1)) and third generation (10(4) voxelss(-1)) are presented and discussed. Three alternative 3rd Generation XDI geometries, namely: direct fan-beam; parallel (waterfall) beam; and inverse fan-beam are compared with respect to technological realization. Directions for future development of XDI in screening applications are outlined.


Assuntos
Medidas de Segurança , Difração de Raios X/métodos , Entorpecentes/análise , Terrorismo/prevenção & controle
12.
Health Technol Assess ; 12(22): iii-iv, ix-155, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18505668

RESUMO

OBJECTIVES: To determine whether GPs should advise their older patients with chronic knee pain to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: An equivalence study was designed to compare the effect of advice to use preferentially oral or topical ibuprofen (an NSAID) on knee pain and disability, NSAID-related adverse effects and NHS/societal costs, using a randomised controlled trial (RCT) and a patient preference study (PPS). Reasons for patient preferences for topical or oral preparations, and attitudes to adverse effects, were explored in a qualitative study. SETTING: Twenty-six general practices in the UK. PARTICIPANTS: Participants comprised 585 people with knee pain, aged 50 years or over; 44% were male, mean age 64 years. The RCT had 282 participants: 144 in the oral group and 138 in the topical group. The PPS had 303 participants: 79 in the oral group and 224 in the topical group. INTERVENTIONS: Advice to use preferentially oral or topical NSAIDs for knee pain. OUTCOME MEASURES: The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the Short Form with 36 Items (SF-36), perceived troublesomeness of knee pain, satisfaction with health status, major adverse effects (unplanned hospital admissions and deaths) and minor adverse events over 12 months. The health economic analysis measured the comparative cost per quality-adjusted life-year (QALY) from both an NHS and a societal perspective over 1 and 2 years. RESULTS: Changes in the global WOMAC score at 12-months were equivalent in both studies: topical - oral, RCT difference=2 [95% confidence interval (CI) -2 to 6], PPS difference=1 (95% CI -4 to 6). There were no differences in the secondary outcomes, except for a suggestion, in the RCT, that those in the topical group were more likely to have more severe overall pain and disability as measured by the chronic pain grade, and more likely to report changing treatment because of inadequate pain relief. There were no differences in the rate of major adverse effects but some differences in the number of minor ones. In the RCT, 17% and 10% in the oral and the topical group, respectively, had a defined respiratory adverse effect (95% CI of difference -17% to -2.0%); after 12 months, the change in serum creatinine was 3.7 mmol/l (95% CI 0.9 to 6.5) less favourable in the oral than in the topical group, and 11% of those in the oral group reported changing treatment because of adverse effects compared with 1% in the topical group (p=0.02). None of these differences were seen in the PPS. Oral NSAIDs cost the NHS 191 pounds and 72 pounds more per participant over 1 year in the RCT and PPS respectively. In the RCT the cost per QALY in the oral group, from an NHS perspective, was in the range 9000-12,000 pounds. In the PPS it was 2564 pounds over 1 year, but over 2 years the oral route was more cost-effective. Patient preference for medication type was affected by previous experience of medication (including adverse reactions), other illness, pain elsewhere, anecdotes, convenience, severity of pain and perceived degree of degeneration. Lack of understanding about knee pain and the action of medication led to increased tolerance of symptoms. Potentially important symptoms may inadvertently have been disregarded, increasing participants' risk of suffering a major adverse effect. CONCLUSIONS: Advice to use either oral or topical preparations has an equivalent effect on knee pain, but oral NSAIDs appear to produce more minor adverse effects than topical NSAIDs. Generally, these results support advising older people with knee pain to use topical rather than oral NSAIDS. However, for patients who prefer oral NSAID preparations rather than a topical NSAID, particularly those with more widespread or severe pain, the oral route is a reasonable treatment option, provided that patients are aware of the risks of potentially serious adverse effects from oral medication. Further research is needed into strategies to change prescribing behaviour and ensure that older patients are aware of the potential risks and benefits of using NSAIDs. Observational studies are needed to estimate rates of different predefined minor adverse effects associated with the use of oral NSAIDs in older people as are long-term studies of topical NSAIDs in those for whom oral NSAIDs are not appropriate.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Ibuprofeno/administração & dosagem , Traumatismos do Joelho/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/farmacologia , Doença Crônica , Aconselhamento , Medicina de Família e Comunidade , Feminino , Humanos , Ibuprofeno/farmacologia , Traumatismos do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Relações Médico-Paciente , Reino Unido
13.
Prim Care Diabetes ; 1(1): 35-41, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18632017

RESUMO

AIMS: To develop and pilot a survey instrument assessing general practitioners' (GP) attitudes to the diagnosis and management of one form of pre-diabetes, impaired glucose tolerance (IGT) and to assess the performance of the questionnaire. METHODS: Qualitative data together with an audit were used to generate questionnaire items, which were then subjected to a process of pre-piloting and piloting to generate a finalised item list. The pilot questionnaire was sent to 222 principal GPs in three PCTs in South West England. The first fifty responders were asked to complete the questionnaire again 2 weeks later. Principal components analysis with a Varimax rotation was used to detect latent factors within the data that may help to explain the attitudes of GPs. RESULTS: The response rate after one reminder was 54.1%. Four robust factors were identified which were internally consistent (range of Cronbach's alpha=0.79-0.65), homogeneous (item-total correlations=0.60-0.21), and stable (test-retest correlation=0.74-0.58) accounting for 31.1% of the variance. The predictive validity of the item list was assessed (P=0.02 for factor 1). CONCLUSIONS: The PAtH questionnaire identifies four factors that help to describe GPs attitudes to the diagnosis and management of IGT.


Assuntos
Atitude do Pessoal de Saúde , Competência Clínica , Hiperglicemia/diagnóstico , Análise Fatorial , Feminino , Humanos , Hiperglicemia/terapia , Masculino , Auditoria Médica , Projetos Piloto , Padrões de Prática Médica , Reprodutibilidade dos Testes , Inquéritos e Questionários , Reino Unido
14.
Cytokine ; 36(1-2): 57-68, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17161616

RESUMO

Osteoporosis and associated fractures are the most common and debilitating complication of glucocorticoid use. The use of alternative anti-inflammatory agents without the deleterious skeletal effects of glucocorticoids is needed. Dehydroepiandrosterone (DHEA) may have immunomodulatory as well as positive effects on bone. For our further understanding of the mechanisms of action of DHEA, as a steroid-sparing agent, we investigated and compared the effects of dexamethasone (DEX) and DHEA on the regulation of the downstream effector pathway of osteoclastogenesis; RANKL/OPG and a range of inflammatory/pro-resorbing cytokines and receptors using a human clonal osteoblastic cell line. The cells were treated with DEX, DHEA, and androstenedione (ANDI). The mRNA expression of RANKL and OPG was determined by real-time PCR after overnight incubation. The regulation of a broad spectrum of cytokines by DEX and DHEA was also investigated using a human cytokine/growth factor and receptor gene array consisting of 268 cytokine-related cDNAs. To confirm some of the gene expression changes, protein production was measured by ELISA. RANKL expression and RANKL/OPG ratio were increased by DEX. This effect was reversed by co-treatment with both DHEA or ANDI. Several pro-inflammatory/resorptive cytokines including IL-6, IL-4, IFN-gamma, macrophage inhibitory factor (MIF) were down-regulated not only by DEX but also by DHEA. In contrast to DEX, DHEA did not lead to suppression of growth factors including vascular endothelial growth factor (VEGF), fibroblast growth factor-5 (FGF-5), insulin-like growth factor-binding protein3 (IGF-BP3). Several new target genes previously documented to influence bone formation were up-regulated by DHEA such as Notch 2, insulin receptor, thrombin receptor (PAR1). The data suggest that DHEA has immunomodulatory properties without the catabolic effects on bone remodeling, observed with glucocorticoid use. DHEA may thus prove useful as a steroid-sparing agent in the management of inflammatory disorders such as SLE or rheumatoid arthritis. Further in vivo studies are indicated.


Assuntos
Citocinas/metabolismo , Desidroepiandrosterona/farmacologia , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Receptores de Citocinas/metabolismo , Androstenodiona/farmacologia , Linhagem Celular , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Osteoclastos/metabolismo , Osteoprotegerina/biossíntese , Osteoprotegerina/genética , Ligante RANK/biossíntese , Ligante RANK/genética , RNA Mensageiro/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese
16.
Histol Histopathol ; 21(6): 633-43, 2006 06.
Artigo em Inglês | MEDLINE | ID: mdl-16528674

RESUMO

Stem cells from fetal and adult central nervous system have been isolated and characterized, providing populations for potential replacement therapy for traumatic injury repair and neurodegenerative diseases. The regenerative capacity of the olfactory system has attracted scientific interest. Studies focusing on animal and human olfactory bulb ensheathing cells (OECs) have heightened the expectations that OECs can enhance axonal regeneration and repair demyelinating diseases. Harvest of OECs from the olfactory bulb requires highly invasive surgery, which is a major obstacle. In contrast, olfactory epithelium (OE) has a unique regenerative capacity and is readily accessible from its location in the nasal cavity, allowing for harvest without lasting damage to the donor. Adult OE contains progenitors responsible for the normal life-long continuous replacement of neurons and supporting cells. Culture techniques have been established for human OE that generate populations of mitotically active neural progenitors that form neurospheres (Roisen et al., 2001; Winstead et al., 2005). The potential application of this technology includes autologous transplantation where minimal donor material can be isolated, expanded ex vivo, and lineage restricted to a desired phenotype prior to/or after re-implantation. Furthermore, these strategies circumvent the ethical issues that arise with embryonic or fetal tissues. The long term goal is to develop procedures through which a victim of a spinal cord injury or neurodegenerative condition would serve as a source of progenitors for his/her own regenerative grafts, avoiding the need for immunosuppression and ethical controversy. In addition, these cells can provide populations for pharmacological and/or diagnostic evaluation.


Assuntos
Regeneração Nervosa , Bulbo Olfatório/citologia , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/fisiologia , Células Cultivadas , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Glicoproteínas de Membrana/análise , Proteínas do Tecido Nervoso/análise , Nestina , Doenças Neurodegenerativas/terapia , Bulbo Olfatório/química , Bulbo Olfatório/fisiologia , Mucosa Olfatória/química , Mucosa Olfatória/citologia , Mucosa Olfatória/fisiologia , Periferinas , Receptores de Fator de Crescimento Neural/análise , Traumatismos da Medula Espinal/terapia , Células-Tronco/química , Tubulina (Proteína)/análise
17.
World J Urol ; 24(1): 61-5, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16389540

RESUMO

BACKGROUND: Asymptomatic bacteriuria is common in diabetic women. Treatment of asymptomatic bacteriuria is not beneficial, but the natural history of the microbiology of asymptomatic bacteriuria has not been well described. OBJECTIVE: To describe the microbiological outcomes of bacteriuria in diabetic women with untreated asymptomatic bacteriuria. METHODS: Study subjects were initially identified through ambulatory endocrinology clinics. They were enrolled if they had two positive urine cultures > or = 10(8) cfu/l with the same organism within 2 weeks and no symptoms referable to urinary tract infection. Women initially received a 2-week course of placebo with follow-up cultures obtained at the end of treatment and 4 weeks post-treatment. Subsequently, the prevalence of bacteriuria was determined with urine cultures obtained every 3 months to a maximum of 36 months. Outcomes at yearly intervals were designated as one of: persistent bacteriuria; spontaneous resolution; resolution with antibiotics for symptomatic urinary infection; or resolution with antibiotics given for other indications. Women with and without persistent or frequent bacteriuria were compared to identify variables associated with bacteriuria. RESULTS: The prevalence of bacteriuria in the study cohort declined to about 50% by 9 months, and subsequently remained stable throughout 3 years follow-up. Almost 20% of subjects remained bacteriuric with the original infecting organism throughout the period of observation. With evaluation at 12-month intervals, approximately one-quarter of subjects had each of the four potential outcomes of: resolution following antibiotic therapy for symptomatic urinary infection, following antibiotic therapy for other indications, spontaneous resolution without antibiotics, and persistent bacteriuria with the same organism. Women infected with gram-negative organisms were more likely to have persistent bacteriuria. Many women with resolution of initial bacteriuria, with or without antibiotics, became bacteriuric again during follow-up. CONCLUSIONS: Women with asymptomatic bacteriuria and diabetes tend to have persistent or recurrent asymptomatic bacteriuria. Bacteriuria is benign, and seldom permanently eradicable.


Assuntos
Bacteriúria/tratamento farmacológico , Bacteriúria/microbiologia , Diabetes Mellitus/diagnóstico , Placebos/administração & dosagem , Infecções Urinárias/microbiologia , Adulto , Distribuição por Idade , Idoso , Anti-Infecciosos Urinários/administração & dosagem , Bacteriúria/epidemiologia , Intervalos de Confiança , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Urinálise , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia
18.
Rheumatology (Oxford) ; 45(6): 751-6, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16418201

RESUMO

OBJECTIVES: To explore the views of participants in a randomized controlled trial of physical treatments for low back pain about the treatment packages they received in the trial. METHODS: Within a randomized controlled trial that found small to moderate benefits from adding a manipulation package or an exercise programme to general practice care, we elicited participants' views on the treatment using an open question in participant questionnaires. These data were analysed using an adapted framework approach. RESULTS: We received a total of 1259 comments from 1334 participants. Participants randomized to usual general practice care reported dissatisfaction with receiving only 'usual care', which consisted of providing analgesic medication without providing an explanation for their pain. Those randomized to a manipulation package felt the intervention was appropriate to their needs and commonly reported striking benefits. Participants assigned to the exercise programme developed a sense of self-reliance in managing back pain, although some failed to be sufficiently motivated to continue their exercise regimen outside the classes. CONCLUSIONS: This qualitative analysis has found much clearer differences between the groups than the main quantitative analysis. This suggests that some of the added value from being allocated to additional physical treatment for low back pain is not being captured by existing methods of measurement. Improved methods of assessment that consider a wider range of domains may be needed when interpreting the added value of such treatments to individual patients.


Assuntos
Dor Lombar/reabilitação , Satisfação do Paciente , Modalidades de Fisioterapia/psicologia , Adolescente , Adulto , Analgésicos/uso terapêutico , Terapia Combinada , Terapia por Exercício , Medicina de Família e Comunidade/normas , Seguimentos , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/psicologia , Pessoa de Meia-Idade , Manipulações Musculoesqueléticas/psicologia , Resultado do Tratamento
19.
Anim Reprod Sci ; 95(3-4): 251-61, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16289553

RESUMO

The Gulf Coast Native sheep, or Louisiana Native sheep, is an endangered previously feral domestic sheep population of European origin that has been under natural selection pressure for reproductive survival in their transplanted range while roaming in the southern Gulf Coast Region of the United States. This sheep population has an increased natural resistance to internal parasites, breeds year-around and has a greater percentage of live lambs as compared with other breeds of sheep raised in similar environments. To preserve the genetic diversity of this important feral sheep population, semen was collected by electro-ejaculation and subjected to cryopreservation for subsequent storage in a genome resource bank. Unrelated rams (n=5) were collected 3 days-a-week, allowing at least 2 days of rest between collections. Two ejaculates were obtained from each ram per collection day, with the second collection conducted 10min after the first ejaculation. Semen was processed using the standard Salamon cryopreservation procedure in a Tris-yolk-glycerol extender, frozen in 0.5ml plastic straws using liquid nitrogen (LN(2)) vapor and stored in LN(2). Each ejaculate was evaluated for volume, sperm concentration/ml (x10(9)/ml), number of spermatozoa/ejaculate (x10(9)), sperm progressive motility (%) for pre-cooled semen, cooled semen and semen after thawing. For the five rams, each semen variable for the first ejaculate was compared with that of the second ejaculate collected 10min later. The mean semen volume, sperm concentration and number of spermatozoa per ejaculate obtained from the first ejaculate were significantly greater (P< or =0.01) than those of the second ejaculate (comparisons being 1.62 and 1.06; 3.2 and 1.5; 5.4 and 1.8, respectively). Overall, the mean motility of pre-cooled (22 degrees Celsius), cooled (5 degrees Celsius) and frozen (-196 degrees Celsius) post-thawed spermatozoa was less (P< or =0.01) in the first ejaculate (71.5, 64.8 and 34.1%, respectively) compared with that of the second ejaculate (75, 72.4 and 44.1%, respectively). Conversely, no differences were detected in loss in the percent progressive motility of sperm from cooled sperm to post-thaw sperm from the first and second ejaculates. In summary, our findings suggest sperm collected during the second ejaculate 10min after the first ejaculate of rams survives thawing with a greater rate of progressive motility than that of the first ejaculate. The ability to collect two consecutive ejaculates in a short period by electro-ejaculation could be valuable for gamete resource banking and preserving genetic diversity of the Gulf Coast Native sheep.


Assuntos
Criopreservação/veterinária , Preservação do Sêmen/veterinária , Sêmen/fisiologia , Ovinos/fisiologia , Animais , Conservação dos Recursos Naturais , Ejaculação , Estimulação Elétrica , Temperatura Alta , Louisiana , Masculino , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/anormalidades , Fatores de Tempo
20.
Haemophilia ; 10(1): 34-41, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14962218

RESUMO

No disease-specific tool for measuring health-related quality of life (HRQL), an important outcome when assessing medical treatment, has been developed for children with haemophilia. The goal of this study was to develop a parent-administered questionnaire for evaluating quality of life (QOL) in paediatric haemophilia patients between 2 and 6 years of age. After interviewing physicians (5), nurses (5) and parents (10) of children with haemophilia aged between 2 and 6 years, 92 questions were developed and pilot-tested with parents (44) of children with haemophilia to create a 39-question instrument that assessed somatic symptoms, physical functioning, sleep disturbance, stigma, social functioning, fear/resentment, mood/behaviour, restrictions, treatment upset, haemophilia concern and energy level. Reliability and validity were evaluated with 103 parents of children with haemophilia and parents of 249 age- and gender-matched healthy children. Estimates of scale reliability (internal consistency) for eight multi-item scales ranged from 0.73 to 0.94. Results showed construct validity (correlations with age, severity of haemophilia, treatment type, days absent and days confined to bed) and correlated with two general, paediatric quality-of-life instruments (Impact on Family Scale and Functional Status II). Discriminant validity was demonstrated by comparing scores between patients receiving/not receiving prophylactic therapy and between haemophilia patients and healthy controls. This disease-specific HRQL measure should be of use in clinical trials and general practice to better understand disease and treatment impacts in young children with haemophilia.


Assuntos
Hemofilia A/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Criança , Pré-Escolar , Humanos , Lactente , Sensibilidade e Especificidade
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