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Biomedical subjects

R Fitzpatrick

Publications and source records attributed to R Fitzpatrick.

At least 37 records · Page 2Linked to original sources

Determining minimally important differences for the PDQ-39 Parkinson's disease questionnaire.

OBJECTIVE: To determine minimally important differences for dimensions of the PDQ-39, a 39-item Parkinson's disease questionnaire. A minimally important difference is defined as the smallest change between two scores that is subjectively meaningful to patients. Data on minimally important differences are essential for the calculation of sample sizes in trials and surveys. METHODS: We conducted a postal survey of randomly selected members of 13 local branches of the Parkinson's Disease Society, asking them to complete the PDQ-39 on two occasions, 6 months apart. On the first occasion respondents received the PDQ-39, demographic questions and a request to provide their name and address if they were willing to take part in the follow-up survey. After 6 months, we sent those who had agreed another copy of the questionnaire and also asked them to indicate how much change they had experienced since baseline in overall health and in each of the eight domains of the questionnaire. RESULTS: We calculated minimally important difference for each dimension and the index score for those reporting minor change since baseline. The minimally important difference varied across dimensions. CONCLUSIONS: These results indicate the minimum magnitude of change that should be sought when designing studies to evaluate change over time in Parkinson's disease. Since minimally important differences differ across dimensions, those designing studies in which sample size calculations are based on the PDQ-39 as an outcome measure should select the dimension which is the primary variable of interest.

Adult↗

The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure.

Changes in health policy have underlined the importance of evidence-based clinical practice and rigorous evaluation of patient-based outcomes. As patient-based outcome measurement is particularly important in treatment trials of multiple sclerosis, a number of disease-specific instruments have been developed recently. One limitation of these instruments is that none was developed using the standard psychometric approach of reducing a large item pool generated from people with multiple sclerosis. Consequently, an outcome measure for clinical trials of multiple sclerosis that is disease specific and combines patient perspective with rigorous psychometric methods will complement existing instruments. The aim of this study was to develop such a measure. Standard psychometric methods were used. A pool of 129 questionnaire items was generated from interviews with 30 people with multiple sclerosis, expert opinion and literature review. The questionnaire was administered by postal survey to 1530 people selected randomly from the Multiple Sclerosis Society membership database. Redundant items and those with limited measurement properties were removed. The remaining items (n = 41) were grouped into scales using factor analysis, and then refined to form the Multiple Sclerosis Impact Scale (MSIS-29), an instrument measuring the physical (20 items) and psychological (nine items) impact of multiple sclerosis. Five psychometric properties of the MSIS-29 (data quality, scaling assumptions, acceptability, reliability and validity) were examined in a separate postal survey of 1250 Multiple Sclerosis Society members. A preliminary responsiveness study of the MSIS-29 was undertaken in 55 people admitted for rehabilitation and intravenous steroid treatment of relapses. The MSIS-29 satisfied all psychometric criteria. Data quality was excellent, missing data were low (maximum 3.9%), item test-re-test reliability was high (r = 0.65-0.90) and scale scores could be generated for >98% of respondents. Item descriptive statistics, item convergent and discriminant validity, and factor analysis indicated that it was legitimate to generate scores for MSIS-29 scales by summing items. MSIS-29 scales showed good variability, small floor and ceiling effects, high internal consistency (Cronbach's alpha <or=0.91) and high test-re-test reliability (intraclass correlation <or=0.87). Correlations with other measures and the analysis of group differences provided evidence that the MSIS-29 measures the physical and psychological impact of multiple sclerosis. Effect sizes (physical scale = 0.82, psychological scale = 0.66) demonstrated preliminary evidence of good responsiveness. These results indicate the MSIS-29 is a clinically useful and scientifically sound patient-based outcome measure of the impact of multiple sclerosis suitable for clinical trials and epidemiological studies.

Evidence-Based Medicine↗

GT160-246, a toxin binding polymer for treatment of Clostridium difficile colitis.

GT160-246, a high-molecular-weight soluble anionic polymer, was tested in vitro and in vivo for neutralization of Clostridium difficile toxin A and B activities. Five milligrams of GT160-246 per ml neutralized toxin-mediated inhibition of protein synthesis in Vero cells induced by 5 ng of toxin A per ml or 1.25 ng of toxin B per ml. In ligated rat ileal loops, 1 mg of GT160-246 neutralized fluid accumulation caused by 5 microg of toxin A. At doses as high as 80 mg/loop, cholestyramine provided incomplete neutralization of fluid accumulation caused by 5 microg of toxin A. GT160-246 protected 80% of the hamsters from mortality caused by infection with C. difficile, whereas cholestyramine protected only 10% of animals. Treatment of C. difficile-infected hamsters with metronidazole initially protected 100% of the hamsters from mortality, but upon removal of treatment, 80% of the hamsters had relapses and died. In contrast, removal of GT160-246 treatment did not result in disease relapse in the hamsters. GT160-246 showed no antimicrobial activity in tests with a panel of 16 aerobic bacteria and yeast and 22 anaerobic bacteria and did not interfere with the in vitro activities of most antibiotics. GT160-246 offers a novel, nonantimicrobial treatment of C. difficile disease in humans.

Animals↗

Reduced item set for the amyotrophic lateral sclerosis assessment questionnaire: development and validation of the ALSAQ-5.

OBJECTIVE: The 40 item amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-40) is a subjective health measure designed specifically to assess areas of importance to patients with ALS. It was designed for use in surveys and clinical trials of this patient group, and has been assessed for reliability and validity. Despite its relative brevity there are situations where an even shorter form of the instrument would be desirable. Consequently, this paper reports a process of item reduction which results in a brief five item version of the instrument. METHODS: Data from two surveys of patients with ALS who completed the ALSAQ-40 were analysed to develop a short form ALSAQ. Questionnaire items were correlated with their dimension total scores. Highly correlated items were transformed onto a scale from 0 to 100 and results compared with the parent dimension. RESULTS: Five items were selected that produced results that closely resembled those of the five dimension scores of the ALSAQ-40. CONCLUSIONS: Results on the new measure compared with the parent ("gold standard") ALSAQ-40 suggest that the measure can produce similar results to the longer form but with considerable economy.

Adult↗

Can item response theory reduce patient burden when measuring health status in neurological disorders? Results from Rasch analysis of the SF-36 physical functioning scale (PF-10).

BACKGROUND: Indices of physical function may have a hierarchy of items. In cases where this can be demonstrated it may be possible to reduce patient burden by asking them to complete only those items which relate directly to their own level of ability. OBJECTIVES: To determine whether statistical procedures, operationalising what is known as item response theory (IRT), can be used to assess the unidimensionality of the 10 item physical functioning domain of the SF-36 in patients with Parkinson's disease and motor neuron disease, and, secondly, to determine whether it would be possible to administer subsets of items to certain patients, on the basis of their replies to other items in the scale, thereby reducing patient burden. METHODS: Rasch analysis, a form of IRT methodology, of the 10 item physical functioning domain (PF-10) in two neurological patient samples was undertaken and the results compared with results of a Rasch analysis of data gained from a population survey (the third Oxford healthy lifestyles survey). RESULTS: Evidence from the analyses suggests that the PF-10 does not form a perfect hierarchy on a unidimensional scale. However, certain items seem to form a hierarchy, and responses to some of them are contingent on responses to the other items. CONCLUSIONS: Rasch analysis of the PF-10 in neurological patients has indicated that certain items of the scale are hierarchically ordered, and consequently not all respondents would need to complete them all: indeed those most severely ill would be required to complete less items than those with only limited disabilities. The implications of this are discussed.

Activities of Daily Living↗

The SF-36 in multiple sclerosis: why basic assumptions must be tested.

OBJECTIVES: To evaluate, in people with multiple sclerosis, two psychometric assumptions that must be satisfied for valid use of the medical outcomes study 36-item short form health survey (SF-36): the data are of high quality and, it is legitimate to generate scores for eight scales and two summary measures using the standard algorithms. METHODS: SF-36 data from 438 people representing the full range of multiple sclerosis were examined (mean age 48; 70% women). Data quality (per cent missing data and computable scale and summary scores) were determined, six scaling criteria were tested to determine the legitimacy of generating the eight SF-36 scale scores using Likert's method of summed ratings, and two scaling criteria were tested to determine the appropriateness of the standard SF-36 algorithms for weighting scale scores to generate two summary measures. RESULTS: Data quality was excellent except in the most disabled subgroup where missing responses reached a maximum of 16.5% and summary scores could only be computed for 72%. There was clear support for the generation of SF-36 scale scores. Item response distributions were symmetric, item mean scores and variances were equivalent, corrected item-total correlations were high (range 0.46-0.85) and similar, and definite scaling success rates exceeded 96%. Nevertheless, there were notable floor or ceiling effects in four of the eight scales. Assumptions for generating two SF-36 summary measures were only partially satisfied. Although principal components analysis suggested a two component model, these components explained less than 60% of the total variance in SF-36 scales, and less than 75% of the variance in five of the eight scales. Moreover, scale to component correlations did not support the use of scale weights derived from United States population data. CONCLUSIONS: When using the SF-36 as a health measure in multiple sclerosis summary scores should be reported with caution.

Activities of Daily Living↗

The benefits of using patient-based methods of assessment. Medium-term results of an observational study of shoulder surgery.

We carried out a prospective study of 93 patients undergoing surgery for conditions of the rotator cuff during 1994 and 1995. They were assessed before operation and after six months, and four years, using the patient-based Oxford Shoulder Score (OSS), the SF-36 questionnaire and the Constant shoulder score. The response rates were higher for the OSS and SF-36. The correlation coefficients were high (r > 0.5) between all scores at each stage of the study. While all scores improved substantially at six months, the Constant score was reduced significantly at four years. This did not correlate with the patients' judgement of the change in symptoms or of the success of the operation. Our study suggests that patient-based measures of pain and function can reliably assess outcomes in the medium term after surgery to the shoulder.

Humans↗

Evidence for the validity of a patient-based instrument for assessment of outcome after revision hip replacement.

The Oxford hip score (OHS) is a patient-based instrument for assessment of outcome which is often used after total hip replacement, and the EuroQol 5D (EQ5D) is a patient-based generic questionnaire for health assessment. In an analysis of the outcome at one year of 609 revision hip replacements (RHRs), we compared the OHS and EQ5D scores, postoperative patient satisfaction and change in pain. About 25% of the operations were repeat RHRs. At one year, 57% of patients were very pleased with their operation. The correlation between preoperative and postoperative scores and change scores for the OHS and EQ5D was high. For both instruments the effect sizes were large, but the greater effect size of the OHS suggests that it is particularly sensitive to improvements after RHR. The effect scores of the OHS declined with the number of previous RHRs, while those for the EQ5D seemed less sensitive. Our results confirm the value of the OHS in assessing outcome after RHR.

Arthroplasty, Replacement, Hip↗

Issues in methodological research: perspectives from researchers and commissioners.

OBJECTIVES: (1) Methodological research has few well-defined tools and processes analogous to those available for reviews and data collection in substantive health technology assessment. (2) This project was set up to obtain researchers' and others' views on the innovative projects on research methodology under the NHS Health Technology Assessment Programme and the usefulness of the research. (3) The study was intended to span both epistemological and management issues. (4) The following issues were explored: (a) the degree to which researchers would feel constrained by the "Cochrane" approach to systematic reviews when undertaking reviews of a methodological nature; (b) whether methodological projects may require exceptional design and management arrangements, in view of their novelty, subjectivity and complexity; (c) whether researchers would seek out other methods, in addition to undertaking reviews of argument, as a means of extending their understanding of methodological issues (there may be three categories of research methods in methodology: reviews of methodological argument, studies that use the literature as a source of data, and research that collects new primary data); (d) whether the Methodology Programme overall can be considered a "success". METHODS: (1) Telephone interviews were carried out on researchers (one senior and one junior per project), resulting in 35 interviews from 19 of the 20 target projects. (2) A qualitative postal survey was sent to 12 people who had played a key role in the development of the Methodology Programme; replies were received from six of them. (3) Analysis was undertaken of the hit rates for 29 projects on the NCCHTA website by the end of February and the end of May 1999, comparing those concerned with methodology (n = 10) and those concerned with other issues (n = 19). RESULTS: UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS: This section summarises the views of 35 researchers who were interviewed by telephone. RESULTS: UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS: (THE NATURE OF METHODOLOGICAL REVIEWS): (1) There was a reluctance among researchers to use the term "systematic review" in the methodological context. (2) Practical problems in undertaking methodological reviews were found at every stage of the research process. (a) In the initial search stage, preplanned strategies were difficult to maintain, owing to the need to respond to the problems of too few or too many references. (b) At the analysis stage, most studies were not formally weighted, but there was implicit weighting in researchers' views of their merits or relevance. (c) It was often only at the synthesis stage that researchers could see clearly what their study was able to do; iteration was frequently necessary at this point. (d) It was difficult to form simple conclusions and recommendations beyond summaries of what was known in the field. (e) Dissemination activities were most often directed to other health service researchers, with some attention to NHS policy makers and research commissioners. RESULTS: UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS (THE NEED FOR FLEXIBILITY): (1) Few researchers had amended their topic or methods once their research was under way, although some had made minor changes to their original plan, generally to refine the topic to fit the time or data available. (2) Changing a topic was seen as inappropriate unless checked with funders, but changes in research methods were viewed as reasonable because questions might be refined in the light of information gained or early thinking. RESULTS: UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS (THE QUESTION OF BIAS): (1) Few researchers considered that this kind of research could be undertaken or presented in a wholly unbiased way because of the need to assess the research studied. (2) Objectivity was nonetheless seen as something that researchers should strive towards. Efforts to do so included presenting data clearly, separating findings from discussion, covering all points of view, setting out their own assumptions and values, and testing their ideas on others known to have differing views. (3) The formal peer-review process was not seen to have made a difference here, primarily because of the stage at which referees become involved. RESULTS: UNDERTAKING METHODOLOGICAL RESEARCH: VIEWS OF RESEARCHERS (PROJECT MANAGEMENT--TIMING AND TIME MANAGEMENT): (1) A majority of projects were completed within 3 months of their due date. Those studies completed roughly on time were considered to have efficient junior researchers and good project management, including clear deadlines for different stages of the research. (2) Some studies had severe problems of time management. Too much time tended to be spent on collecting and reading the literature and the writing stage was not always well planned. Referees' comments were also slow in coming. (ABSTRACT TRUNCATED)

Attitude↗

Primary total hip replacement: variations in patient management in Oxford & Anglia, Trent, Yorkshire & Northern 'regions'.

OBJECTIVES: To examine national practice, and variations in practice, concerning total hip replacement; in particular the choice of prosthesis and the involvement of consultants in NHS operations. DESIGN: Pre-operative survey of patients undergoing total hip replacement. SETTING: Five English regions serving combined population of 16.8 million people. SUBJECTS: 13,343 total hip replacement operations in one year commencing September 1996, either in NHS or private sector. MAIN OUTCOME MEASURES: Prosthesis used for surgery, status of surgeons involved in operation, use of laminar flow operating theatre. RESULTS: Prostheses without well documented 5-year survival were used in 5504 (58%) of 9417 operations for which information was available. The consultant was the operator in 4810 (64%) of 7499 NHS operations. In 1352 trainee-led operations, the consultant was present for only 637 (47%); this figure was 54% for trainees in years 1-4 of their training. Substantial variation between NHS consultant firms occurred both for use of prostheses with well documented survival data, and supervision of trainees by the consultant. CONCLUSIONS: This large study is the first attempt to describe national practice for primary total hip replacement. Substantial variation among consultant firms was observed for all indices of practice reported.

Adult↗

The amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-40): tests of data quality, score reliability and response rate in a survey of patients.

OBJECTIVES: To evaluate response rate, data quality, and score reliability of the 40 item Amyotrophic Lateral Sclerosis Assessment Questionnaire in a survey of MND patients. DESIGN: A survey of members of the MND Association of the UK, of which half were randomly allocated to receive a survey instrument from the MND Association and the other half allocated to receive the MND Association survey instrument and also the ALSAQ-40 questionnaire. SAMPLE: Five hundred patients were randomly selected from the membership lists of the MND Association, of whom 250 received the MND Association Survey and the ALSAQ-40. RESULTS: Response rate to the survey was 59.2%. Over half of the respondents received the ALSAQ-40. Data for individual items were analysed and found to be distributed across all response categories. All items were found to be highly associated with the scales to which they contribute. Internal consistency reliability of all the five scales of the ALSAQ-40 was also found to be high. CONCLUSION: Inclusion of the ALSAQ-40 into the survey did not have an adverse effect upon response rates. Furthermore, the ALSAQ-40 was shown to have highly desirable psychometric properties. This paper provides further evidence of the reliability and validity of the measure.

Adult↗

Comparing health inequality in men and women: prospective study of mortality 1986-96.

OBJECTIVES: To study prospectively the differences in health inequality in men and women from 1986-96 using the Office for National Statistics' longitudinal study and new socioeconomic classification. To assess the relative importance of social class (based on employment characteristics) and social position according to the general social advantage of the household to mortality risk in men and women. DESIGN: Prospective study. SETTING: England and Wales. SUBJECTS: Men and women of working age at the time of the 1981 census, with a recorded occupation. MAIN OUTCOME MEASURES: Mortality. RESULTS: In men, social class based on employment relations, measured according to the Office for National Statistics' socioeconomic classification, was the most important influence on mortality. In women, social class based on individual employment relations and conditions showed only a weak gradient. Large differences in risk of mortality in women were found, however, when social position was measured according to the general social advantage in the household. CONCLUSIONS: Comparisons of the extent of health inequality in men and women are affected by the measures of social inequality used. For women, even those in paid work, classifications based on characteristics of the employment situation may give a considerable underestimate. The Office for National Statistics' new measure of socioeconomic position is useful for assessing health inequality in men, but in women a more important predictor of mortality is inequality in general social advantage of the household.

Age Distribution↗

The ALS Health Profile Study: quality of life of amyotrophic lateral sclerosis patients and carers in Europe.

The measurement of functioning and well-being from the perspective of the patient has in recent years become central to the assessment of health and the evaluation of treatment regimes. The past decade has seen an enormous growth in the application of measures designed to assess quality of life in a vast array of medical specialties. However, the use of such measures in neurology has been relatively limited, and this has certainly been the case in amyotrophic lateral sclerosis (ALS). The European ALS Health Profile Study is a longitudinal survey of patients diagnosed with ALS or other motor neurone diseases in which patients are asked to complete questionnaires concerning their subjective health status. Data from clinical assessments are also collected. It is intended that the information collected will provide more systematic and detailed evidence of the impact of the disease from the perspective of the patient. This contribution documents results from baseline assessment obtained from data supplied by clinicians, carers and patients themselves. Three outcome measures are assessed in this paper: the SF-36, a generic measure of well being and functioning, the ALS Functional Rating Scale and the Carer Strain Index. The evidence presented here suggests that these measures provide a meaningful and valid picture of the impact of the disease. The data indicate that ALS has substantial adverse effects both upon the functioning and well being of patients and carers, as well as an association between the emotional health status of patients and carers, and between the physical health status of patients and carers.

Adult↗

Cell Culture Evaluation of the Semliki Forest Virus Expression System As a Novel Approach for Antigen Delivery and Expression in Fish.

Heterologous gene expression by Semliki Forest virus (SFV) expression vectors was investigated in fish cell culture. Experiments performed using an infectious strain of SFV, replication-defective SFV particles, and recombinant SFV RNA constructs encoding the Escherchia coli LacZ or firefly luciferase reporter genes indicated that levels of SFV-mediated expression in fish cells were dependent on cell type and temperature. Maximal expression levels were observed in the two salmonid-derived cell lines CHSE-214 and F95/9 at 25 degrees C and 20 degrees C. As the temperature was lowered to 15 degrees C or below, levels of reporter gene expression were reduced up to 1000-fold, indicating that the SFV replication complex functioned inefficiently at low temperatures. The ability of SFV expression systems to function in fish cells was further investigated by analyzing the expression of the protective VP2 antigen of infectious pancreatic necrosis virus (IPNV) from the various constructs, including a novel DNA-based SFV plasmid. The VP2 protein produced in CHSE-214 and F95/9 cells transfected or infected with the recombinant SFV-IPNV VP2 constructs appeared to be synthesized in an antigenically correct form, as evidenced by the ability to react with several conformation-dependent IPNV-specific monoclonal antibodies. Whether the temperature-restricted replication and expression displayed by SFV-based constructs in fish cell culture also occurs in vivo remains to be determined.

Journal Article↗

Social distribution of cardiovascular disease risk factors: change among men in England 1984-1993.

OBJECTIVE: To investigate change in the social distribution of some of the main risk factors for cardiovascular disease in men in England during a period when inequality in cardiovascular disease mortality widened DESIGN: Age standardised comparison of the social distribution of seven known risk factors for cardiovascular disease (body mass index, waist to hip ratio, systolic and diastolic blood pressure, consumption of fresh green vegetables, leisure time exercise, cigarette smoking and levels of social support) in two large cross sectional representative samples of the English population. SUBJECTS: Men aged 20-64 years in the 1984 Health and Lifestyle Survey (excluding Scotland and Wales) first sweep and the 1993 Health Survey for England. MAIN OUTCOME MEASURES: Mean values of continuous variables; age adjusted proportions of categorical variables; change in the relative index of inequality for each risk factor. RESULTS: The overall prevalence of cardiovascular disease risk factors improved during the period in which cardiovascular disease mortality was falling. The social distribution of cardiovascular disease risk factors, in contrast, did not become more extreme. Increases in the relative index of inequality for angina from 1.75 to 1.86, for eating vegetables less than once a day from 1.76 in 1984 to 1.96 in 1993, and an apparently larger increase in inequality of social support, from 1.92 to 2.53 were not statistically significant. In most cases the degree of inequality in risk factors tended to narrow non-significantly: for example the relative index of inequality fell from 5.02 in 1984 to 3.07 in 1993 for systolic blood pressure, from 5.60 to 4.29 for current smoking and from 6.24 to 4.19 for eating other than wholemeal bread as the main form of bread in the diet. The two statistically significant changes in inequality were in the direction of narrowing inequality: from a relative index of inequality of 2.12 to 0.90 for diastolic blood pressure (p<0.01) and from 19.3 to 0.87 (p<0.01) for psychological distress as indicated by the General Health Questionnaire. CONCLUSIONS: Healthier lifestyle options have not been adopted at a significantly faster rate by middle class than working class people over this time period. At the population level the change in risk factors is consistent with falling cardiovascular mortality. The change in the social distribution of risk factors within the population, however, shows little or no relation to the pattern of widening inequality in cardiovascular mortality. This may be because the effect is lagged, or because the adoption of healthier behaviour confers greater benefits on those in higher socioeconomic status groups.

Adult↗