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Biomedical subjects

A Cranney

Publications and source records attributed to A Cranney.

At least 37 records · Page 2Linked to original sources
PubMed2001

Etidronate for treating and preventing postmenopausal osteoporosis.

OBJECTIVES: To systematically review the efficacy of etidronate on bone density, fractures and toxicity in postmenopausal women. SEARCH STRATEGY: We searched MEDLINE from 1966 to December 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. SELECTION CRITERIA: We included thirteen trials (with 1010 participants) that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least one year. DATA COLLECTION AND ANALYSIS: For each trial, three independent reviewers assessed the methodological quality and abstracted data. MAIN RESULTS: The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.60% (95% CI 0.41 to 0.88). There was no effect on non-vertebral fractures (pooled relative risk 1.00, (95% CI 0.68 to 1.42)). Etidronate, relative to control, increased bone density after three years of treatment in the lumbar spine by 4.27% (95% CI 2.66 to 5.88), in the femoral neck by 2.19% (95% CI 0.43, 3.95) and in the total body by 0.97% (95% CI 0.39, 1.55). Effects were larger at 4 years, though the number of patients followed was much smaller. REVIEWER'S CONCLUSIONS: Etidronate increases bone density in the lumbar spine and femoral neck. The pooled estimates of fracture reduction with etidronate are consistent with a reduction in vertebral fractures, but no effect on non-vertebral fractures.

Bone Density↗
PubMed2001

A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.

The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1-3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

Aged↗
PubMed2001

Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation.

OBJECTIVE: To assess the cost effectiveness of nasal calcitonin (Miacalcin) compared with no therapy, alendronate or etidronate in the treatment of postmenopausal women with previous osteoporotic fracture. DESIGN AND SETTING: Meta-analysis followed by economic analysis. PERSPECTIVE: A Canadian provincial Ministry of Health. METHODS: The meta-analysis of randomised controlled clinical trials was based on the recommendations of the Cochrane Collaboration. Economic analysis was conducted within a Markov model using probabilities and costs derived from Canadian sources. RESULTS: The meta-analysis found evidence of the positive effect of both nasal calcitonin and alendronate in reducing the risks of hip, wrist and vertebral fractures in postmenopausal women. However, there was a lack of evidence of the effect of etidronate on hip and wrist fractures. For a 65-year-old woman, with 5 years' therapy, the incremental cost per quality-adjusted life-year (QALY) gained for nasal calcitonin was 46,500 Canadian dollars ($Can) compared with no therapy and $Can32,600 compared with etidronate (1998 values). Comparison with alendronate was highly sensitive to the inclusion of one specific trial. CONCLUSIONS: Given the results of the analysis, based on current evidence, nasal calcitonin can be considered at the margins of being cost effective when compared with no therapy. Compared with active therapy, nasal calcitonin can be considered more cost effective than etidronate, but its cost effectiveness versus alendronate is inconclusive.

Aged↗
PubMed2001

The psychometric properties of patient preferences in osteoporosis.

OBJECTIVE: Osteoporosis is a chronic disease manifested by wrist, vertebral, and hip fractures that results in significant morbidity and burden to society. About 30% of postmenopausal women have osteoporosis according to the WHO criteria. Women with one vertebral fracture have a 4-fold increased risk of a subsequent fracture. The goal of treatment is to prevent fractures and improve quality of life. Preferences or utilities are now recommended for incorporating quality of life into evaluations of the cost effectiveness of new therapeutic interventions. We evaluated the psychometric properties of preference based measures in osteoporosis. METHODS: Preference scenarios were constructed with a health state classification system. The reliability and validity of the feeling thermometer and the standard gamble was assessed by interviewing 42 women from 4 different patient groups. The sensitivity to change of the feeling thermometer and standard gamble was compared with the Health Utilities Index Mark 2 (HUI2) and SF-36. All subgroups were reassessed about 2 months after their first interview. RESULTS: Preference measurement was feasible in women of different age groups. The reliability coefficients for health states ranged from 0.65 to 0.87. The preference scores for the marker states demonstrated content validity. Convergent validity of the feeling thermometer was supported by a significant correlation with the HUI2 (r = 0.38, p < 0.05) and the physical health summary of the SF-36 (r = 0.56, p < 0.005). The standard gamble did not correlate with the HUI2 (r = 0.15) or the feeling thermometer (r = 0.09), but correlated with 2 domains of the SF-36. The preference measures were sensitive to change, with the efficiency scores ranging from 0.78 to 1.0. CONCLUSION: Preference measurements in the evaluation of osteoporosis are feasible. The feeling thermometer and standard gamble appear to be related to different aspects of health related quality of life. Both instruments were sensitive to change over a 2 month period.

Aged↗
PubMed2001

Discrimination of changes in osteoporosis outcomes.

The purpose of this paper was to identify existing work related to discrimination, responsiveness, and minimal clinically important differences (MCID) for 4 key clinical outcomes in osteoporosis, to serve as a background to discussions about how to define MCID for both individuals and groups. The outcomes assessed were bone density, fractures, quality of life, and function. We conducted a systematic literature search in MEDLINE, EMBASE, and Current Contents for articles that discussed responsiveness, detectable difference, improvement criteria, and clinical importance. We used the Beaton cube to classify the studies depending on whether they compared differences between or changes within individuals or groups. Although a number of studies were identified that presented data on detectable differences beyond error and observed differences, few studies presented data on how to define clinically important differences. A key priority for future research is to define minimally clinical important differences for clinically important osteoporosis outcomes using a consensus based approach that will be accepted by the osteoporosis community at large. Furthermore, these MCID will likely be different for individual patients seen in clinical practice than for individuals in a clinical trial.

Clinical Trials as Topic↗
PubMed2000

Calcium and vitamin D for corticosteroid-induced osteoporosis.

OBJECTIVES: To assess the effects of calcium and vitamin D compared to calcium alone or placebo in the prevention of bone loss in patients taking systemic corticosteroids. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal trials register, Cochrane Controlled Trials Register, EMBASE and Medline up to 1996. We also conducted a hand search of abstracts from various scientific meetings and reference lists of selected trials. SELECTION CRITERIA: All randomized trials comparing calcium and vitamin D to calcium alone or placebo in patients taking systemic corticosteroids. DATA COLLECTION AND ANALYSIS: Data was abstracted from trials by two investigators. Methodological quality was assessed in a similar manner. Analysis was performed using fixed effects models. MAIN RESULTS: Five trials were included, with 274 patients. The analysis was performed at two years after starting calcium and vitamin D. There was a significant weighted mean difference (WMD) between treatment and control groups in lumbar (WMD 2.6 (95% CI 0.7, 4.5), and radial bone mineral density (WMD 2.5 (95% CI 0.6, 4.4). The other outcome measures (femoral neck bone mass, fracture incidence, biochemical markers of bone resorption) were not significantly different. REVIEWER'S CONCLUSIONS: This meta-analysis demonstrated a clinically and statistically significant prevention of bone loss at the lumbar spine and forearm with vitamin D and calcium in corticosteroid treated patients. Because of low toxicity and cost all patients being started on corticosteroids should receive prophylactic therapy with calcium and vitamin D.

Calcium↗
PubMed2000

Bisphosphonates for steroid induced osteoporosis.

OBJECTIVES: To assess the effects of bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, Medline up to 1997 and Embase1988-1997), and selected hand searching of reference lists was conducted. Hand searching of scientific abstracts from relevant meetings for the last five years was also done. An electronic search in Current Contents was done for the last six months. The Cochrane Controlled Trials Register (CCTR) will be searched for future updates. All languages were included in the search. For practical reasons only those in English were included, but all languages will be retrieved and translated for future updates. SELECTION CRITERIA: All controlled clinical trials (CCTs) dealing with prevention or treatment of corticosteroid-induced osteoporosis with bisphosphonates of any type and reporting the outcomes of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. DATA COLLECTION AND ANALYSIS: All data extraction was performed by two independent reviewers. Outcomes of interest included change in bone mineral density (BMD) at the lumbar spine and femoral neck at six and 12 months. If present, data on number of new fractures and withdrawals due to adverse effects were also extracted. All data extraction was performed by two independent reviewers. Both continuous and dichotomous data were analyzed using fixed effects models. When significant heterogeneity was present, a random effects model was used. MAIN RESULTS: A total of 13 trials, including 842 patients are included in this meta-analysis. Results are reported as a weighted mean difference of the percent change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. The 95% confidence intervals (95% CI) are presented. At the lumbar spine, the weighted mean difference of BMD between the treatment and placebo groups was 4.3% (95% CI 2.7, 5.9). At the femoral neck, the weighted mean difference was 2.1% (95%CI 0. 01, 3.8). Although there was a 24% reduction in odds of spinal fractures [OR 0.76 (95%CI 0.37, 1.53)], this result was not statistically significant. REVIEWER'S CONCLUSIONS: Bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk.

Diphosphonates↗
PubMed2000

Calcitonin for the treatment and prevention of corticosteroid-induced osteoporosis.

BACKGROUND: Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy. OBJECTIVES: To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected RCTs which met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations. MAIN RESULTS: Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for nonvertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing. REVIEWER'S CONCLUSIONS: Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.

Calcitonin↗
PubMed1999

A measure of limited joint motion and deformity correlates with HLA-DRB1 and DQB1 alleles in patients with rheumatoid arthritis.

OBJECTIVE: To assess factors associated with a poor outcome in rheumatoid arthritis (RA), a measure was developed of limited joint motion and deformity, a deformity index (DI), and correlated biochemical and genetic variables with the magnitude of the DI. METHODS: Forty patients were evaluated in a cross sectional study. Clinical measures included the DI and Health Assessment Questionnaire, and disease variables included the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and HLA-DRB1 and DQB1 alleles. RESULTS: Significant correlations were noted between increasing DI and duration of RA and concentration of C reactive protein. Patients with a DQB1*301 allele or DR4 allele had a higher DI than those without, and a positive trend was noted between increasing DI and dose of DRB1 RA susceptibility alleles. The trend was lost when a non-linear regression technique was used to remove the effect attributable to C reactive protein, suggesting an interrelation between persistent inflammation and genetics in determining total joint damage. CONCLUSIONS: The DI may be useful to study interactions between genetic and inflammatory processes in rheumatoid disease progression.

Adult↗
PubMed1999

Validity of area-under-the-curve analysis to summarize effect in rheumatoid arthritis clinical trials.

There is a continuing interest in increasing the statistical efficiency of the analysis of clinically meaningful endpoints in rheumatology. One issue that is attracting increasing attention is whether the conventional practice of only reporting the outcome at the end of the study (EOS) might be replaced or complemented by a longitudinal summary that better reflects the clinical course of the disease. The area under the curve (AUC) is a summary measure that integrates serial assessments of a patient's endpoint over the duration of the study. We evaluated the utility of AUC as a summary measure for the analysis and reporting of two RA trials: (i) methotrexate combined with cyclosporine versus methotrexate and placebo in partial methotrexate responders in relatively late disease, and (ii) prednisone plus methotrexate plus sulfasalazine versus sulfasalazine alone in relatively early disease. We replicated the published results of each trial first using the conventional EOS and then AUC summaries. For each patient, the changes from baseline over time were transformed into a summary measure by calculating AUC using the trapezium rule and then standardizing it by the study duration. Using an approach similar to the index of responsiveness to change, we scaled treatment differences derived from EOS and AUC summary measures by their standard deviation of the control group. This signal-versus-noise ratio captures the treatment discrimination ability of each summary measure. Compared to EOS and within each treatment group, the AUC summary reported smaller effects (i.e., change from baseline) with reduced errors in the estimates. AUC measures preserved discriminant validity in treatment comparisons and reported smaller but more precise treatment effect estimates. In the COBRA trial with rapidly-acting medications, AUC seemed to be more sensitive than EOS to detect treatment difference. With slow acting medications and in relatively late disease patients as in the cyclosporine trial, EOS was more sensitive to detect treatment difference than was AUC. In this setting, AUC, however, still seemed to be more sensitive than EOS for the two responsive-to-change endpoints: tender joint counts and pain by visual analog scale. AUC integrates repeated assessments during the trial duration into summary measures. Compared to EOS, the report of RA trial results using AUC summary provides smaller estimates of treatment effects but with better precision. AUC summary is likely to preserve treatment group discrimination taking into account the appropriate onset and offset of the drug action. Trial reports using AUC summary have smaller effect sizes. For trials with long acting medications and short duration similar to the cyclosporine trial, AUC still preserves treatment discrimination but may not be as sensitive as EOS. The calculations of AUC require some additional work in the analysis of each endpoint.

Antirheumatic Agents↗
PubMed1999

A metaanalysis on the use of bisphosphonates in corticosteroid induced osteoporosis.

OBJECTIVE: To conduct a metaanalysis on the use of bisphosphonates in corticosteroid induced osteoporosis. METHODS: A Cochrane systematic review including electronic database searching (MEDLINE and EMBASE), and selected hand searching of reference lists and scientific abstracts was conducted. Metaanalysis using random and fixed effects modeling was used on the selected trials to calculate summary effect measures. All controlled clinical trials dealing with prevention or treatment of corticosteroid induced osteoporosis with bisphosphonates of any type and reporting the outcome of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. Outcomes of interest were change in bone mineral density (BMD) at the lumbar spine and femoral neck at 6 and 12 months. If present, data on number of new fractures and adverse effects were also extracted. The extraction was performed by 2 independent reviewers. RESULTS: Results are reported as a weighted mean difference in the percentage change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. At the lumbar spine the weighted mean difference between the treatment and placebo groups was 4.0% (95% CI 2.5, 5.5). At the femoral neck the weighted mean difference was 2.1% (95% CI 0.2, 4.0). Although there was a 24% reduction in spinal fractures, this result did not reach statistical significance. CONCLUSION: Bisphosphonates are effective at preventing and treating corticosteroid induced bone loss at the lumbar spine. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk. Bisphosphonates are less efficacious at preventing or treating corticosteroid induced osteoporosis at the femoral neck.

Adrenal Cortex Hormones↗
PubMed1999

Responsiveness of endpoints in osteoporosis clinical trials--an update.

As an update of our earlier paper, published as part of the Outcome Measures in Rheumatology Clinical Trials (OMERACT 3) proceedings in 1996, we surveyed the types of outcomes incorporated in recent clinical trials. A literature search was conducted on MEDLINE and Current Contents, from January 1996 to March 1998, using the search strategy recommended by the Cochrane Collaboration for the identification of randomized controlled trials (RCT). Two independent reviewers selected trials according to inclusion criteria. The same reviewers extracted data on clinical and radiographic fractures, pain, quality of life, and bone mineral density (BMD). Seventy-four RCT conducted on bone loss in postmenopausal women were identified. Most trials incorporated biochemical markers and BMD as outcome measures. Fewer trials included vertebral fractures, pain, height, and quality of life. The responsiveness is presented in terms of the sample size needed per group to show a statistically significant difference. The most responsive outcomes were pain, BMD, and biochemical markers. The number needed to treat to prevent one vertebral fracture ranged from 13 to 54, depending on the intervention and population. Investigators should examine the characteristics of the patient population and the nature of the intervention in determining the sample size required to demonstrate a significant effect. The selection of endpoints should be based on their responsiveness, feasibility, and the importance of using standardized outcomes. Standardized outcomes greatly facilitate the synthesis of available information into systematic reviews by groups such as the Cochrane Collaboration.

Antirheumatic Agents↗
PubMed1998

The use of Neoral in rheumatoid arthritis.

Neoral (a microemulsion-based formulation) is an immunomodulator that possesses a more predictable and improved absorption than the conventional oral formulation (Sandimmun). The increased bioavailability of Neoral could result in improved efficacy. The pharmacokinetics of cyclosporin and efficacy of cyclosporin in rheumatoid arthritis are reviewed in this article. Current guidelines for the use of Neoral in the treatment of rheumatoid arthritis patients are outlined.

Antirheumatic Agents↗
PubMed1997

Implications of OMERACT outcomes in arthritis and osteoporosis for cochrane metaanalysis.

The Cochrane Collaboration has established a set of methods for pooling multiple studies assessing the same intervention. Assessing the same endpoints in all studies is important to allow different trials to be combined using metaanalysis. OMERACT can play a key role in establishing consensus on the use of common endpoints that are credible to clinicians. We describe the data that need to be included in individual trial reports for metaanalyses to be carried out.

Arthritis↗