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Biomedical subjects

M M Ward

Publications and source records attributed to M M Ward.

At least 19 recordsLinked to original sources
PubMed2006

Outcomes in ankylosing spondylitis: what makes the assessment of treatment effects in ankylosing spondylitis different?

There are four major challenges in the assessment of outcomes in patients with ankylosing spondylitis (AS) that are particularly relevant to the evaluation of new therapies. Firstly, measures of symptoms and impairment in AS are not specific for inflammatory processes, they also capture mechanical symptoms and fixed limitations. The non-specific nature of these measures may cause them to be less responsive and therefore less useful in determining treatment efficacy. Secondly, acute phase reactants have limited value as measures of AS activity and other surrogate markers have not yet been established. Thirdly, the assessment of the disease modifying potential of new therapies is hampered by the slow rate of spinal fusion. Fourthly, work disability has not be studied as an endpoint in clinical trials in AS, despite the fact that work disability is an important outcome in patients with AS. Research into ways to overcome these challenges in outcome measurement will help identify useful therapies and define the range of outcomes that they influence.

Biomarkers↗
PubMed2005

Duration of rheumatoid arthritis influences the degree of functional improvement in clinical trials.

BACKGROUND: Functional capacity is an important outcome in rheumatoid arthritis and is generally measured using the Health Assessment Questionnaire disability index (HAQ). Functional limitation incorporates both activity and damage. Because irreversible damage increases over time, the HAQ may be less likely to show improvement in late than in early rheumatoid arthritis. OBJECTIVE: To determine the relation between sensitivity to change of the HAQ and duration of rheumatoid arthritis in reports of clinical trials. METHODS: Data were pooled from clinical trials that measured responses of HAQ scores at three or six months. The effect size of the HAQ was calculated and linear regression used to predict the effect size by duration of rheumatoid arthritis at group level. Treatment effect was adjusted for by including the effect sizes of pain scores and of tender joint counts as additional independent variables in separate models. Subgroup analysis employed contemporary regimens (methotrexate, leflunomide, combination therapies, and TNF inhibitors) only. RESULTS: 36 studies with 64 active treatment arms and 7628 patients (disease duration 2.5 months to 12.2 years) were included. The effect sizes of the HAQ decreased by 0.02 for each additional year of mean disease duration using all trials, and by 0.04/year in the subgroup analysis (p<or=0.01 for both analyses, except for pain adjusted models at three months). CONCLUSIONS: In individual trials, less improvement in the HAQ might be expected in late than in early rheumatoid arthritis. Comparison of changes in HAQ among rheumatoid arthritis trials should take into consideration the disease stage of the treated groups.

Adult↗
PubMed2005

Glutamate uptake in retinal glial cells during diabetes.

AIMS: Glutamate recycling is a major function of retinal Muller cells. The aim of this study was to evaluate the expression and function of glutamate transporters during diabetes. METHODS: Sprague-Dawley rats were rendered diabetic by a single dose of streptozotocin (50 mg/kg). Following 12 weeks of diabetes, immunolocalisation and mRNA expression of the two glial cell transporters, GLAST and EAAT4 were evaluated using indirect immunofluorescence and real-time PCR. The function of glutamate transport was investigated at 1, 4 and 12 weeks following induction of diabetes by measuring the level of uptake of the non-metabolisable glutamate analogue, D: -aspartate, into Muller cells. RESULTS: There was no difference in the localisation of either GLAST or EAAT4 during diabetes. Although there was a small apparent increase in expression of both GLAST and EAAT4 in diabetic retinae compared with controls this was not statistically significant. At 1, 4 and 12 weeks following diabetes, D: -aspartate immunoreactivity was significantly increased in Muller cells of diabetic rats compared to controls (p<0.001). The EC(50) was found to increase by 0.304 log units in diabetic Muller cells compared with controls, suggesting that glutamate uptake is twice as efficient. CONCLUSIONS: These data suggest that there are alterations in glutamate transport during diabetes. However, these changes are unlikely to play a significant role in glutamate-induced neuronal excitoxicity during diabetes. These results suggest that although Muller cells undergo gliosis at an early stage of diabetes, one of the most important functions for maintaining normal retinal function is preserved within the retina.

Amino Acid Transport System X-AG↗
PubMed2004

Effect of dietary copper source (cupric citrate and cupric sulfate) and concentration on growth performance and fecal copper excretion in weanling pigs.

In each of two experiments, 924 pigs (4.99 kg BW; 16 to 18 d of age) were assigned to 1 of 42 pens based on BW and gender. Pens were allotted randomly to dietary copper (Cu) treatments that consisted of control (10 ppm Cu as cupric sulfate, CuSO4 x 5H2O) and supplemental dietary Cu concentrations of 15, 31, 62, or 125 ppm as cupric citrate (CuCit), or 62 (Exp. 2 only), 125 (Exp. 1 only), or 250 ppm as CuSO4. Live animal performance was determined at the end of the 45-d nursery phase in each experiment. On d 40 of Exp. 2, blood and fecal samples were collected from two randomly selected pigs per pen for evaluation of plasma and fecal Cu concentrations and fecal odor characteristics. In Exp. 1, ADG, ADFI, and G:F were increased (P < 0.05), relative to controls, when pigs were fed diets containing 250 ppm Cu as CuSO4. Pigs fed diets containing 125 ppm Cu as CuCit had increased (P < 0.05) ADG compared with pigs fed diets supplemented with 15 or 62 ppm Cu as CuCit. The ADG, ADFI, and G:F did not differ among pigs fed diets containing 125 and 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. In Exp. 2, pigs fed diets containing 250 ppm Cu as CuSO4 had improved (P < 0.05) ADG, ADFI, and G:F compared with controls. In addition, ADG, ADFI, and G:F were similar when pigs were fed diets containing either 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. Pigs fed diets containing 62 ppm Cu as CuSO4 or CuCit had similar ADG, ADFI, and G:F. Plasma Cu concentrations were not affected by dietary Cu source or concentration, but fecal Cu concentrations were increased (P < 0.05) as the dietary concentration of Cu increased. Pigs consuming diets supplemented with 125 ppm Cu as CuCit had fecal Cu concentrations that were lower (P < 0.05) than pigs consuming diets supplemented with 250 ppm Cu as CuSO4. Fecal Cu did not differ in pigs receiving diets supplemented with 62 ppm Cu as CuSO4 or CuCit. Odor characteristics of feces were not affected by Cu supplementation or source. These data indicate that 125 and 250 ppm Cu gave similar responses in growth, and that CuCit and CuSO4 were equally effective at stimulating growth and improving G:F in weanling pigs. Fecal Cu excretion was decreased when 125 ppm Cu as CuCit was fed compared with 250 ppm Cu as CuSO4. Therefore, 125 ppm of dietary Cu, regardless of source, may provide an effective environmental alternative to 250 ppm Cu as CuSO4 in weanling pigs.

Animal Feed↗
PubMed2003

Time perspective predicts the progression of permanent organ damage in patients with systemic lupus erythematosus.

Patients whose perspective is oriented to the future more than to the present may have better long-term health outcomes. We examined if time perspective predicted future organ damage in patients with systemic lupus erythematosus (SLE). We assessed the time perspectives of 87 patients with SLE using a questionnaire at a baseline visit. Permanent organ damage was assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index during the same visit, and reassessed after a median of 4.6 years. Patients who were oriented more to the future were less likely to have an increase in the Damage Index than those oriented more to the present. In a multivariate analysis, each 1-point increase in the degree of orientation to the future (on a scale of 1-6) was associated with a 22% decrease in the likelihood that the Damage Index would increase over time (odds ratio 0.78; 95% confidence interval 0.64-0.94; P = 0.009). Other measures that predicted an increase in the Damage Index were lower education levels, greater health locus of control attributed to chance and greater health locus of control attributed to powerful others. In conclusion, time perspective is a significant predictor of future organ damage in SLE. Patients who have a greater orientation to the future are less likely to develop permanent organ damage.

Adult↗
PubMed2002

Psychological distress and changes in the activity of systemic lupus erythematosus.

OBJECTIVE: To determine if changes in depressive symptoms or anxiety lead to changes in the activity of systemic lupus erythematosus (SLE). METHODS: Twenty-three patients with SLE were examined prospectively every 2 weeks for up to 40 weeks. At each assessment, patients completed the Centers for Epidemiologic Studies--Depression scale (CES-D), the State subscale of the State-Trait Anxiety Inventory and a global assessment of the activity of their SLE by visual analogue scale. SLE activity was also assessed at each visit by physician global assessment, the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure (ECLAM). RESULTS: Changes in depression and anxiety were positively correlated with simultaneous changes in the patient global assessment of SLE activity and in the SLAM, but not with changes in the physician global assessment, SLEDAI or ECLAM. Depression and anxiety scores were also correlated with patient global assessments and SLAM scores 2 weeks later, but lagged scores were not significantly associated with the patient global assessment or SLAM after controlling for current depression and anxiety scores. The associations between depression and anxiety scores and the SLAM were not present when SLAM scores were modified to exclude ratings of depression and fatigue. No measure of SLE activity increased in the 2 weeks immediately after a large increase in CES-D or State Anxiety scores. CONCLUSIONS: Depression and anxiety scores parallel changes in patients' assessments of the activity of their SLE. We found no evidence to support the hypothesis that psychological distress causes increased SLE activity.

Adult↗
PubMed2001

Mortality and causes of death in systemic lupus erythematosus.

Cohort studies of survival in systemic lupus erythematosus (SLE) often have been limited by methodologic problems. In studies of inception cohorts of patients followed since 1980, survival at 5 years has exceeded 90%. These estimates are generally higher than survival estimates from earlier studies, suggesting that short-term survival in SLE has improved. There is less evidence to support major improvements over time in survival after 10 years or more of SLE. Infections, atherosclerotic disease, and active systemic lupus erythematosus or organ damage caused by SLE are the main causes of death in patients with SLE, but the proportion of early deaths caused by active SLE has decreased over time.

Bacterial Infections↗
PubMed2001

Risk factors for work disability in patients with ankylosing spondylitis.

OBJECTIVE: To identify risk factors for work disability in patients with ankylosing spondylitis (AS). METHODS: Risk factors for permanent work disability and for receipt of disability payments were assessed using Cox regression models in a retrospective cohort study of 234 patients with AS. Candidate risk factors included age at onset of AS, sex, race, education level, marital status, the presence of comorbid conditions, smoking and drinking history, recreational activity, occupation, and physical activity at work. Risk factors for changes in the type of work performed, decrease in number of hours worked, long sick leave, and the need for help at work were assessed using logistic regression models in a prospective study of the subset of 144 patients who reported working for pay during the study. Candidate risk factors for these aspects of work disability were age, sex, race, education level, levels of functional disability, pain and stiffness, changes in functional disability, pain or stiffness over the preceding 6 months, minutes/week of recreational exercise, back exercises, freedom of movement at work, control over the pace of work, and physical activity at work. RESULTS: In a cohort of 234 patients with a median duration of AS of 21.4 years, 31 patients (13.2%) developed permanent work disability and 57 patients (24.3%) had received disability payments. Older age at onset of AS, less formal education, and having had jobs that were more physically active were significant risk factors for permanent work disability. These factors, along with the presence of a comorbid condition and being female, were also significantly associated with the receipt of disability payments. In a prospective study of 144 patients followed for a median of 4 years, higher levels of functional disability and pain were associated with increased risks of decreased work hours, long sick leaves, and needing help at work, while higher levels of pain were also associated with an increased risk of changing the type of work performed. Women were significantly more likely than men to change their type of work or decrease their work hours. Patients whose jobs were more physically demanding were more likely to change their type of work or need help at work. CONCLUSION: Patients with AS who have physically demanding jobs are more likely to experience permanent or temporary work disability, or need to change the type of work done or receive help at work, than those with jobs that are less physically demanding.

Adult↗
PubMed2000

Changes in the incidence of end-stage renal disease due to lupus nephritis, 1982-1995.

BACKGROUND: The availability of more effective treatments for severe lupus nephritis may have influenced the rate at which end-stage renal disease (ESRD) develops in these patients. OBJECTIVE: To examine changes in the incidence of ESRD due to lupus nephritis from 1982 to 1995. METHODS: All patients with incident ESRD included in the US Renal Data System from 1982 to 1995 were studied. The US Renal Data System includes information on all patients who receive Medicare-reimbursed renal replacement therapy, who constitute approximately 94% of all patients with ESRD in the United States. The incidence of ESRD due to lupus nephritis in each year, standardized to the age-sex-ethnicity composition of the US general population in 1990, was computed in this serial cross-sectional study. RESULTS: The standardized incidence rate of ESRD due to lupus nephritis increased steadily from 1.16 cases per million person-years in 1982 to 3.08 cases per million person-years in 1995. The rate of increase was comparable to that of ESRD due to all other primary renal diseases. CONCLUSION: The incidence of ESRD due to lupus nephritis increased steadily over the 14-year study period, despite the introduction of efficacious new treatment regimens for lupus nephritis during this time.

Adult↗
PubMed2000

Exercise and changes in health status in patients with ankylosing spondylitis.

BACKGROUND: Although exercise is a commonly recommended treatment for ankylosing spondylitis (AS), little is known about the effectiveness of unsupervised recreational and back exercises. We examined the effects of recreational exercise and back exercises on patient-reported pain severity, stiffness severity, and functional disability in a prospective longitudinal study of 220 patients with AS. METHODS: Participants provided information on exercise habits and health status every 6 months using mailed questionnaires (median follow-up, 4.5 years). Pain severity and stiffness severity were measured using visual analog scales, and functional disability was measured using the Health Assessment Questionnaire (HAQ) Disability Index. RESULTS: Among all patients, there were no associations between either the number of exercise minutes per week or the number of days of back exercise per week and short-term (6-month) changes in pain, stiffness, or HAQ Disability Index. However, among those who had AS for 15 years or less, pain scores were 0.18 points lower (on a scale of 0-3; P =.04), and stiffness scores were 6.4 points lower (on a scale of 0-100; P =.005) during periods with more than 200 minutes per week of exercise compared with periods with 0 to 30 minutes of exercise per week. Among those who had AS for more than 15 years, pain scores were 0.11 points lower (on a scale of 0-3; P =. 03), and HAQ Disability Indexes were 0.08 points lower (on a scale of 0-3; P<.001) during periods with 5 to 7 days per week of back exercise compared with periods when back exercises were not performed. Less intense levels of exercise were not associated with improvements in health status. CONCLUSIONS: Unsupervised recreational exercise improves pain and stiffness, and back exercise improves pain and function in patients with AS, but these effects differ with the duration of AS. Health status is improved when patients perform recreational exercise at least 30 minutes per day and back exercises at least 5 days per week. Arch Intern Med. 2000;160:2969-2975

Adult↗
PubMed2000

Identification of clinically important changes in health status using receiver operating characteristic curves.

Identification of criterion standards for clinically important changes for groups of patients requires that judgments of the degree of change that represents a clinically important change are consistent among patients. We demonstrate the use of receiver operating characteristic (ROC) curves to test if patients' judgments of clinically important changes are consistent. Twenty-three patients with systemic lupus erythematosus (SLE) were examined prospectively every 2 weeks for up to 40 weeks. At each assessment, each patient rated the activity of their SLE on a visual analog scale, rated whether their SLE was more active, less active, or unchanged over each 2-week interval, and rated the importance of any change in SLE activity. One of three physician examiners completed similar assessments. Each measured change in the patient global assessment was categorized according to the patient's judgment of whether no change in SLE activity was noted or whether the patient thought their SLE was more or less active during the interval. ROC curves were constructed from these data. Areas under the ROC curve that were significantly greater than 0.5 were considered evidence for consistent ratings among patients of important changes in SLE activity. Patient assessments of change were available for 383 of 392 2-week intervals (97.7%). Of these, patients reported no change in SLE activity in 200 intervals, improvement in 72 intervals, and worsening in 111 intervals. Intervals of improvement could be distinguished from intervals of no change by changes in the patient global assessments [ROC area = 0.68; 95% confidence interval (CI) 0. 60, 0.76]. The cutpoint with the greatest sensitivity and specificity for any improvement was a decrease of 5 points or more (on a 0-100 scale) in patient global assessment. Intervals of worsening could also be distinguished from intervals of no change (ROC area = 0.80; 95% CI 0.74, 0.85), and the best cutpoint was an increase of 5 points or more in the patient global assessment. Group criteria for major improvement or worsening and for relative changes in the patient global assessment could also be determined, as could criteria for important changes in physician global assessments. By testing the consistency of patients' judgments of important changes, ROC curves provide a means to determine if group criteria for clinically important change can be established.

Adult↗
PubMed2000

Access to renal transplantation among patients with end-stage renal disease due to lupus nephritis.

Access to living related renal and cadaveric renal transplantation was compared between 5,863 adults with incident end-stage renal disease (ESRD) caused by lupus nephritis and 463,141 adults with other causes of ESRD who were included in the US Renal Data System from 1987 to 1995. Using Cox regression models that adjusted for differences in age, sex, race, region of residence, and year of onset of ESRD, patients with ESRD caused by lupus nephritis were as likely as patients with other causes of ESRD to receive a living related renal transplant (adjusted hazard ratio [HR] = 1.02; 95% confidence interval [CI], 0.93 to 1.10; P = 0.70) but were 20% less likely to receive a cadaveric renal transplant (adjusted HR = 0.80; 95% CI, 0.75 to 0.85; P < 0.0001). Patients with ESRD caused by lupus nephritis were significantly more likely to be entered onto a waiting list for cadaveric renal transplantation (adjusted HR = 1. 15; 95% CI, 1.10 to 1.21; P < 0.0001) but were less likely to receive a cadaveric transplant once entered onto a waiting list (adjusted HR = 0.73; 95% CI, 0.69 to 0.78; P < 0.0001). Patients with ESRD caused by lupus nephritis had equal access to living related renal transplantation and greater enrollment on waiting lists for cadaveric transplantation than patients with ESRD from other causes, indicating that medical ineligibility is not a major barrier to transplantation. Both medical and nonmedical factors may contribute to the decreased likelihood of cadaveric transplantation among patients with ESRD caused by lupus nephritis.

Adult↗
PubMed2000

A comparison of three approaches for attributing hospitalizations to specific diseases in cost analyses.

OBJECTIVES: Calculations of healthcare costs rarely disclose the specific approach used to allocate the cost of hospitalizations by diagnosis. However, the type of approach used can have a major impact on the findings in the case of significant comorbidities. The present analyses compared three approaches for attributing Medicare DRG reimbursements (which were used as surrogates for average costs) for hospitalization by diagnosis. METHODS: Medical resource utilization data from the National Hospital Discharge Survey were analyzed using each of three allocation approaches: a) attributing 100% of the cost of hospitalization to the disease when it was the first-listed diagnosis; b) attributing a portion of the cost of hospitalization to the disease, depending on its position in the list of diagnoses and the relevance of any comorbidities; and c) an incremental analysis of cost based upon the hospitalization experiences of an age and gender matched cohort. These three approaches were applied to the cost of hospitalization for chronic obstructive pulmonary disease (COPD). RESULTS: The first approach projected 206,098 hospitalizations at $3,449 per hospitalization for a projected U.S. annual total of $711 million. The second approach projected 681,547 hospitalizations at $3,205 per hospitalization for a projected U.S. annual total of $2.2 billion. The third approach also projected 681,547 hospitalizations, but at $2,361 per hospitalization, for a projected U.S. annual total of $1.6 billion. CONCLUSIONS: Expanding from the example on COPD, the limitations of each approach are described and their applications to other conditions are presented.

Aged↗