Biomedical subjects

D M Ashcroft

Publications and source records attributed to D M Ashcroft.

16 recordsLinked to original sources

PubMed2006

Reducing variation in antibacterial prescribing rates for 'cough/cold' and sore throat between 1993 and 2001: regional analyses using the general practice research database.

OBJECTIVE: To use the General Practice Research Database (GPRD) to explore the regional variation in prescribing for single diagnostic episodes of 'cough/cold' and sore throat and how this changed between 1993 and 2001. METHODS: Data from the GPRD was used to conduct a longitudinal survey of morbidity and antibiotic prescribing data. RESULTS: Nationally there has been a substantial reduction in diagnosed episodes per 1000 patient years at risk for both diagnoses: from 104.6 (104.0-105.2) to 86.5 (86.0-86.9) for cough/cold (-17.3%) and from 102.8 (102.2-103.4) to 69.2 (68.8-69.6) for sore throat (-32.6%). In addition to the changes in diagnostic rate there have been reductions in diagnosis-related prescribing: from 41.8% to 34.8% of cough/cold episodes (-7.0%) and from 77.3% to 60.8% of sore throat episodes (-16.4%). These aggregated data conceal wide regional variations. For cough/cold the change in prescribing rate during the study varied from -16.0% to +5.3% and for sore throat from -28.3% to -7.3%. CONCLUSIONS: In addition to a substantial reduction in diagnosis of cough/cold and sore throat, there has been a reduction in diagnosis-related prescribing episodes in almost all regions. Although there continues to be regional variation in diagnosis-related prescribing this has reduced substantially over the 9-year study period.

Anti-Bacterial Agents↗

PubMed2006

Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.

AIMS: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. METHODS: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. RESULTS: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. CONCLUSIONS: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.

Adolescent↗

PubMed2006

Interventions for vitiligo.

BACKGROUND: Around 1% of the world's population has vitiligo, which causes a loss of skin colour in patches. The methods currently available to treat vitiligo are largely unsatisfactory and vary widely between cultures and within health systems. OBJECTIVES: To assess the effects of interventions used to manage vitiligo. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED and other databases (last searched September 2004). Reference lists of articles and conference proceedings were searched. Authors of reviews were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed study eligibility and methodological quality and carried out data extraction. The included studies compared different interventions and used different outcome measures so we considered it inappropriate to combine their results. MAIN RESULTS: Nineteen trials with a total of 1350 participants were included. The RCTs generally had low numbers of participants and only RCTs of repigmentation and not other methods of managing vitiligo were able to be included. In one study, potent topical steroids resulted in better repigmentation than placebo and they were also better than oral psoralens plus sunlight in another study (RR 4.70 95% CI 1.14 to 19.39) although their long-term use is limited by adverse effects. Two studies suggested that topical calcipotriol enhanced repigmentation rates from PUVAsol and PUVA when compared with placebo. Another two studies showed higher repigmentation rates with oral PUVAsol versus placebo plus sunlight (RR 19.20 95% CI 1.21 to 304.50 in 79 adults and RR 2.29 95% CI 1.14 to 4.58 in a study of 50 children). The safety of these interventions was poorly described and none of the studies was able to demonstrate long term benefits. Very few studies were carried out on children or included segmental vitiligo. No trials evaluating micropigmentation, melanocyte transplantation, depigmentation or cosmetic camouflage could be found. Despite the fact that the main impact of vitiligo is psychosocial only one study on psychological therapy was found and it is awaiting assessment. AUTHORS' CONCLUSIONS: This review has found some evidence to support existing therapies for vitiligo, but the different designs and outcome measurements, lack of quality of life measures and adverse effect reporting in the studies limit the usefulness of their findings. There is a pressing need for high quality randomised trials using standardised measures of repigmentation and which address relevant clinical outcomes including quality of life.

Humans↗

PubMed2006

Trade-offs between the benefits and risks of drug treatment for psoriasis: a discrete choice experiment with U.K. dermatologists.

BACKGROUND: The choice of drug treatment for an individual patient is a complex matter. In the case of psoriasis there is a range of treatments available, with varying degrees of efficacy and risk of adverse events. OBJECTIVES: To examine the extent to which the attributes of a treatment affect dermatologists' choice of drug therapy and explore the magnitude and nature of the trade-offs between the risks and benefits of treatment. METHODS: A postal questionnaire was sent to members of the British Association of Dermatologists (BAD). The questionnaire used a discrete choice experiment (DCE) to elicit dermatologists' preferences for the treatment of psoriasis. In all, 227 dermatologists completed the questionnaire. The results indicated that time to moderate improvement, time to relapse, risk of hypertension, liver damage, skin cancer and skin irritation were all important factors affecting dermatologists' choice of treatment. Comparing the coefficients for the different side-effects indicated that the dermatologists considered the risk of liver damage to be the most important side-effect, followed by the risk of skin cancer. The time to achieve a moderate (50%) improvement in psoriasis was prioritized over the time to relapse. CONCLUSIONS: This study has provided novel insight into the trade-offs that dermatologists face when selecting treatment for psoriasis patients. Future research should explore the extent to which dermatologists' preferences for treatment match those of psoriasis sufferers.

Adult↗

PubMed2006

Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the risk of cerebrovascular events (CVEs) associated with selective cyclooxygenase-2 inhibitors (coxibs). METHOD: Systematic review and meta-analysis of randomized controlled trials (RCTs). A fixed-effect model was used to estimate the odds ratios (ORs) for risk of CVE associated with coxibs compared against placebo, non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and other coxibs. RESULTS: Forty trials (88 116 patients) were included in the meta-analysis. The overall pooled OR for CVE for any coxib against placebo was 1.03 (95% CI: 0.71, 1.50). Comparing individual coxibs against placebo, we found that celecoxib, rofecoxib, etoricoxib and lumiracoxib were associated with higher CVE risks and valdecoxib was associated with a lower CVE risk, although there were no significant differences detected. There was also no significant difference in risk of CVE when comparing coxibs against any non-selective NSAIDs; the corresponding pooled OR was 0.86 (95% CI: 0.64, 1.16). CONCLUSION: On the basis of a detailed analysis of available RCTs, there does not appear to be any significant difference in risk of CVEs associated with coxibs when compared against placebo or non-selective NSAIDs. It is likely that the increased risk of thrombotic vascular events associated with coxibs is largely attributable to an increased risk of myocardial infarction, rather than CVEs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Likelihood of reporting adverse events in community pharmacy: an experimental study.

BACKGROUND: In the UK the National Reporting and Learning System (NRLS) is designed to coordinate the reporting of patient safety incidents nationally and to improve the ability of the health service to learn from the analysis of these events. Little is known about levels of engagement with the NRLS. OBJECTIVE: To examine the likelihood of community pharmacists and support staff reporting patient safety incidents which occur in community pharmacies. METHODS: Questionnaire survey containing nine incident scenarios. In the scenarios two factors were orthogonally manipulated: the outcome for the patient was reported as good, bad or poor, and the behaviour of the pharmacist was described as either complying with a protocol, not being aware of a protocol (error), or violating a protocol. Respondents were asked to rate whether they would report the incident (1) locally within the pharmacy and (2) nationally to the National Patient Safety Agency (NPSA). RESULTS: 275 questionnaires were returned (79% response rate) from 223 community pharmacists and 52 members of support staff. There were significant main effects for both patient outcome (F(2,520) = 18.19, p<0.001) and behaviour type (F(2,520) = 93.98, p<0.001), indicating that pharmacists and support staff would take into account both the outcome of the behaviour and whether or not it follows a protocol when considering to report an incident within the pharmacy. Likewise, both pharmacists and support staff considered patient outcome (F(2,524) = 12.59, p<0.001) and behaviour type (F(2,524) = 34.82, p<0.001) when considering to report to the NPSA. Both locally and nationally, the likelihood of reporting any incident was low, and judgements on whether to report were more affected by the behaviour of the pharmacist in relation to protocols than the resulting outcome for the patient. CONCLUSIONS: Community pharmacists and their support staff would be unlikely to report adverse incidents if they witnessed them occurring in a community pharmacy. They remain to be convinced that the advantages to them and their patients outweigh the consequences of blame.

Analysis of Variance↗

PubMed2005

Safety culture assessment in community pharmacy: development, face validity, and feasibility of the Manchester Patient Safety Assessment Framework.

OBJECTIVE: To develop a framework that could be used by community pharmacies to self-assess their current level of safety culture maturity, which has high face validity and is both acceptable and feasible for use in this setting. DESIGN: An iterative review process in which the framework was developed and evaluated through a series of 10 focus groups with a purposive sample of 67 community pharmacists and support staff in the UK. MAIN OUTCOME MEASURES: Development of the framework and qualitative process feedback on its acceptability, face validity, and feasibility for use in community pharmacies. RESULTS: Using this process, a version of the Manchester Patient Safety Assessment Framework (MaPSAF) was developed that is suitable for application to community pharmacies. The participants were able to understand the concepts, recognised differences between the five stages of safety culture maturity, and concurred with the descriptions from personal experience. They also indicated that they would be willing to use the framework but recognised that staff would require protected time in order to complete the assessment. CONCLUSIONS: In practice the MaPSAF is likely to have a number of uses including raising awareness about patient safety and illustrating any differences in perception between staff, stimulating discussion about the strengths and weaknesses of patient safety culture within the pharmacy, identifying areas for improvement, and evaluating patient safety interventions and tracking changes over time. This will support the development of a mature safety culture in community pharmacies.

England↗

PubMed2004

Systematic review of the analgesic efficacy and tolerability of COX-2 inhibitors in post-operative pain control.

OBJECTIVE: To evaluate the relative analgesic efficacy and tolerability of single-dose COX-2 inhibitors in post-operative pain management. METHOD: Systematic review of randomized controlled trials (RCTs). OUTCOME MEASURES: The area under the pain relief vs. time curve was used to evaluate the proportion of patient achieving at least 50% pain relief using validated equations. The proportions of patients experiencing any adverse event or specific adverse events were also examined. RESULTS: In all, 18 RCTs were included which contained 2783 patients. The results of the effects of single-dose analgesics on the basis of 50% of patients achieving pain relief over 6 h from dental pain models suggested that oral rofecoxib 50 mg was more effective than codeine/paracetamol 60/600 mg, and the rate ratio (RR) was 2.11 (95% CI 1.6-2.75). Valdecoxib 40 mg was also more effective than oxycodone/paracetamol 10/1000 mg (RR 1.34; 95% CI 1.11-1.62). There was no significant differences between other oral COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs), except that celecoxib 200 mg was less effective than ibuprofen 400 mg (RR 0.66; 95% CI 0.48-0.90) and rofecoxib 50 mg (RR 0.65; 95% CI 0.49-0.87). The results from orthopaedic pain model showed no significant difference between rofecoxib 50 mg and naproxen sodium 550 mg (RR 1.04; 95% CI 0.73-1.49). The adverse effects of single-dose COX-2 inhibitor used in short-term post-operative pain management were generally mild and less than non-selective NSAIDs, although there was no significant difference. CONCLUSIONS: The analgesic efficacy and tolerability of single-dose COX-2 inhibitors were more effective than opioid-containing analgesics and similar to non-selective NSAIDs in post-operative pain management. Further studies are needed to examine the efficacy and tolerability of COX-2 inhibitors compared against active comparators over a longer duration to assess whether these short-term effects are mirrored by longer-term outcomes and to determine their ultimate risk-benefit profile.

Analgesics, Non-Narcotic↗

PubMed2000

Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis.

OBJECTIVES: To evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis. DESIGN: Quantitative systematic review of randomised controlled trials. SUBJECTS: 6038 patients with plaque psoriasis reported in 37 trials. MAIN OUTCOME MEASURES: Mean difference in percentage change in scores on psoriasis area and severity index, and response rate ratios for both patients' and investigators' overall assessments of marked improvement or better. Adverse effects were estimated with the rate ratio, rate difference, and number needed to treat. RESULTS: Calcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol. CONCLUSIONS: Calcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids are needed to see whether these short term benefits are mirrored by long term outcomes such as duration of remission and improvement in quality of life.

Administration, Topical↗

PubMed2000

Combination regimens of topical calcipotriene in chronic plaque psoriasis: systematic review of efficacy and tolerability.

OBJECTIVE: To examine the efficacy and tolerability of calcipotriene combined with phototherapy or systemic therapies compared with monotherapy for the treatment of chronic plaque psoriasis. DESIGN: Quantitative systematic review of 11 randomized controlled trials involving a total of 756 patients with plaque psoriasis. MAIN OUTCOME MEASURES: Rate ratios (RRs) for marked improvement or clearance in patient and investigator overall assessments of response; mean difference in percentage change in Psoriasis Area and Severity Index; and RRs for clearance in patient and investigator overall assessments of response. Adverse effects were estimated with the RR and the rate difference in terms of withdrawal rate, proportion of patients experiencing adverse events, and proportion of patients with cutaneous and noncutaneous adverse effects. RESULTS: Antipsoriatic effects of acitretin, cyclosporine, and psoralen-UV-A phototherapy were enhanced with the addition of topical calcipotriene using the Psoriasis Area and Severity Index as the outcome, but this is not translated into an increase in the number of patients who achieve at least marked improvement. At the end of treatment, the RRs for marked improvement or clearance in patient assessments were as follows: calcipotriene plus acitretin vs acitretin alone (12 weeks), 1.4 (95% confidence interval [CI], 1.0-1. 9); calcipotriene plus cyclosporine vs cyclosporine alone (6 weeks), 1.2 (95% CI, 0.9-1.6); and calcipotriene plus psoralen-UV-A vs psoralen-UV-A alone (12 weeks), 1.2 (95% CI, 0.9-1.6). Patients were also no more likely to obtain marked improvement or better with calcipotriene plus UV-B therapy than with UV-B therapy alone (RR, 1. 0; 95% CI, 0.8-1.1 at 8 weeks in the patient assessment). There is limited evidence that use of calcipotriene might reduce the cumulative exposure to phototherapy and systemic treatment. During the short duration of these trials, there were no significant differences in withdrawal rates or adverse effects between the combined regimens and their corresponding monotherapy control interventions. CONCLUSIONS: Overall, there is insufficient evidence to support any large effects in favor of combination treatment. In the patient assessments, the results do not show an adjuvant effect, but there is some evidence that use of calcipotriene might reduce cumulative exposure to systemic therapy to obtain clearance. There were no long-term morbidity data on the effectiveness of any of the combinations studied. Given that psoriasis is a chronic recurrent disease for most patients, longer trials are needed to determine whether the addition of topical calcipotriene to systemic therapy improves the risk-benefit ratio by reducing the long-term risk of toxic effects. Equally important is the need to examine the impact of such combinations on the duration of remission after treatment.

Administration, Cutaneous↗

PubMed2000

Therapeutic strategies for psoriasis.

Psoriasis is a chronic, inflammatory, hyperproliferative skin disease that affects approximately 1-2% of the general population in the U.K. and U.S.A. It is rarely life-threatening, but causes considerable patient morbidity. The disease waxes and wanes, with substantial variability both between and within individual patients. There is no cure for psoriasis; therefore, the aim of treatment is to minimize the extent and severity of the disease to the point at which it no longer disrupts substantially the patient's quality of life. We review the current treatment options, which include topical therapies, phototherapy and systemic agents. Lack of efficacy, adverse effects and aesthetic problems limit the use of many topical therapies. Likewise, the risk of toxicity is a major problem with currently available phototherapies and systemic treatments. Advances in understanding the aetiology and pathogenesis of psoriasis allude to the possibility of innovative, targeted therapies in the future.

Administration, Oral↗

PubMed2000

Cost-effectiveness analysis of topical calcipotriol versus short-contact dithranol. In the treatment of mild to moderate plaque psoriasis.

OBJECTIVE: To examine the relative cost effectiveness of topical calcipotriol and short-contact dithranol in the treatment of mild to moderate plaque psoriasis. DESIGN AND SETTING: This was a modelling study from the perspective of the UK National Health Service as payer. METHODS: The interventions were compared using 2 decision-analytic models: one using a short term horizon (12 weeks) and the other using a longer term horizon (up to 1 year). Clinical success of treatment and relapse rates were obtained from the results of randomised controlled trials. MAIN OUTCOME MEASURES AND RESULTS: The outcome measure used was the degree of improvement in psoriasis as judged by the patient. In the short term comparison, calcipotriol was the most effective treatment (60.8% success), but it was also the most expensive (96.03 Pounds; 2000 values). The incremental cost per success was 577.50 Pounds using a 12-week course of calcipotriol compared with short-contact dithranol. Over the long term horizon, first-line treatment with calcipotriol still had the highest expected cost per successful treatment (164.91 Pounds), but the incremental cost using this strategy was 38.66 Pounds compared with short-contact dithranol. In terms of cost per successful day's treatment (i.e. the cost for a day in which the patient reported a marked improvement or cleared lesions), the cost of each additional successful day's treatment was 19.93 Pounds when using calcipotriol as first-line treatment rather than short-contact dithranol. CONCLUSION: The combination of differences in drug acquisition costs and relapse rates can lead to large differences in the comparative cost effectiveness of topical treatments for plaque psoriasis. From the perspective of the prescriber, the results of this analysis suggest that selecting short-contact dithranol as first-line treatment was the most cost-effective strategy.

Administration, Topical↗

PubMed1999

Clinical measures of disease severity and outcome in psoriasis: a critical appraisal of their quality.

In clinical trials, a wide range of outcome measures has been used to evaluate the severity of psoriasis and its response to treatment. Despite their widespread use, many measures have received little attention with regards to their reliability and validity. Selecting an appropriately developed measurement tool is therefore of critical importance. We conducted a literature survey to examine the status of clinical outcome measures used in psoriasis research. The measures most commonly used were individual sign scores, e.g. for erythema, plaque thickness or scaling, and pooled indices, e.g. the Psoriasis Area and Severity Index. None of these, however, systematically fulfilled all the requirements of a validated instrument for disease assessment. Ideally, a core set of reliable and validated outcome measures for use in all psoriasis clinical trials is needed. Objective instrumental methods should minimise observer variation, but unless a simple non-invasive method can be developed, the uptake of such technology will probably be limited by cost and lack of practicality. Moreover, the translation of instrumental readings into clinically relevant measures is always a major problem, and for none of the methods has there been a robust mapping of instrumental readings on to a clinically meaningful scale. Further research is needed to determine the most appropriate and sensitive parameters to use as surrogate measures for capturing the distress which psoriatic patients feel but which is not measured with sufficient sensitivity or precision with current quality of life or distress questionnaires.

Outcome Assessment, Health Care↗

PubMed1999

Herbal remedies: issues in licensing and economic evaluation.

In recent years, the use of alternative therapies has become widespread. In particular, there has been a resurgence in the public's demand for herbal remedies, despite a lack of high-quality evidence to support the use of many of them. Given the increasing pressures to control healthcare spending in most countries, it is not surprising that attention is being focused on the cost effectiveness of herbal remedies. We address the question of whether there is sufficient information to enable the assessment of the cost effectiveness of herbal remedies. In so doing, we discuss the current state of play with several of the more high-profile alternative herbal remedies [Chinese medicinal herbs for atopic eczema, evening primrose oil, ginkgo biloba, hypericum (St John's wort)] and some which have made the transition from being alternative to being orthodox remedies. We use historical context to discuss, on the one hand, the increasing commodification of herbal remedies and on the other, the trend towards greater regulatory control and licensing of alternative herbal remedies. We argue that unless great care is exercised, these changes are not necessarily in the best interests of patients. In order to identify cost-effective care, we need reliable information about the costs as well as the efficacy and safety of the treatments being assessed. For most alternative therapies, such data are not available. We believe that studies to gather such data are long overdue. Whilst we argue strongly in favour of control of some herbal remedies, we urge caution with the trend towards licensing of all herbal remedies. We argue that the licensing of those herbal remedies with equivocal benefits and few risks, as evidenced by a long history of safe use, increases barriers to entry and increases societal healthcare costs.

Complementary Therapies↗

PubMed1998

Quality of life measures in psoriasis: a critical appraisal of their quality.

In recent years, the importance of patient-generated evaluations in assessing the impact of healthcare has been recognized. A plethora of quality of life (QoL) instruments have been developed to measure the burden of psoriasis and its treatment on the patient. We review the QoL measures and provide a critical appraisal of their quality. There is considerable variation in how the instruments have been constructed, the categories and items included, and the methods by which their reliability and validity have been examined. In order to guide investigators in their choice of instrument, further head-to-head comparisons of measures should be undertaken. When QoL measures are compared, a Pearson or rank-order correlation coefficient is not sufficient to indicate agreement. Methods that examine agreement, rather than association, are available and should be used. In the future, we will need to demonstrate whether these measurement tools are ready for widespread implementation in clinical trials or routine patient follow-up.

Data Collection↗

PubMedDate not supplied

Upper gastroduodenal ulceration in arthritis patients treated with celecoxib.

OBJECTIVE: To evaluate the comparative incidence of endoscopic gastroduodenal ulcers in patients with rheumatoid arthritis or osteoarthritis treated with celecoxib. DESIGN: Quantitative systematic review of randomized controlled trials. SUBJECTS: Patients (n = 4632) with rheumatoid arthritis or osteoarthritis reported in five trials. MAIN OUTCOME MEASURES: Rate ratios, rate differences, and the number needed to harm were calculated for the incidence of endoscopically documented gastroduodenal ulcers. RESULTS: Pooled rate ratios (RRs) relative to placebo for endoscopic ulcers at 12 weeks were 1.96 (95% CI 0.85 to 4.55) for celecoxib 100 mg twice daily and 2.35 (95% CI 1.02 to 5.38) for celecoxib 200 mg twice daily. There was no significant difference in gastroduodenal ulcers at 12 weeks between celecoxib 200 mg twice daily and celecoxib 100 mg twice daily; the corresponding pooled RR was 1.21 (95% CI 0.62 to 2.38). In contrast, celecoxib 200 mg twice daily was associated with a significantly lower rate of gastroduodenal ulcers than was naproxen 500 mg twice daily at 12 weeks (RR 0.24; 95% CI 0.17 to 0.33). On average, for every seven patients treated with naproxen, one more had an endoscopic ulcer than if they were treated with celecoxib. Celecoxib 200 mg twice daily also had a significantly lower risk of endoscopic ulcers than did either modified-release diclofenac 75 mg twice daily at 24 weeks (RR 0.24; 95% CI 0.11 to 0.52) or ibuprofen 800 mg three times daily at 12 weeks (RR 0.30; 95% CI 0.20 to 0.46). CONCLUSIONS: Endoscopic studies have shown that celecoxib, at a wide range of doses, is associated with a lower incidence of gastroduodenal ulcers than are diclofenac, ibuprofen, or naproxen. The incidence rates of gastroduodenal ulcers associated with celecoxib were similar, although not equivalent, to placebo. Head-to-head comparisons suggest that, at the wide range of doses studied (100-800 mg/d), there are no dose-related increases in endoscopic gastroduodenal ulcers with celecoxib. The results of longer term comparative trials of celecoxib based on clinical outcomes are needed to determine celecoxib's ultimate risk-benefit profile.

Anti-Inflammatory Agents, Non-Steroidal↗