Anti-tubercular therapy (ATT) induced thrombocytopenia: A systematic review.

INTRODUCTION: Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol. MATERIALS AND METHODS: We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review. RESULTS: Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment. DISCUSSION: ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management. CONCLUSION: This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.

Efficacy and safety of aspirin as an adjunctive therapy in tubercular meningitis: A systematic review and meta-analysis.

BACKGROUND: Tubercular meningitis (TBM) is associated with high mortality and stroke with chronic neurological sequelae even with best of care and antitubercular therapy. Studies have shown that aspirin as an adjunctive therapy might play some role in management of TBM. This systematic review and meta-analysis has been planned to evaluate the efficacy and safety of aspirin as an adjunctive therapy in TBM patients. METHODS: We conducted a systematic search of randomized controlled trials in patients with tubercular meningitis published till October 2019 in all major clinical journals. Study was registered with PROSPERO with registration number: CRD42019136689. Articles were tested for eligibility and assessed for quality and various bias. Data synthesis and analysis was done using Review manager 5.3. The primary end point for assessment of efficacy was mortality at three months. The secondary end point was stroke or composite outcome of stroke and mortality at three months. Adverse effects were also assessed as secondary safety end point. FINDINGS: Overall, three eligible randomized controlled trials with 365 participants were included that provided quantitative data for this meta-analysis. The analysis of primary and secondary end points was done using fixed effect model. There was not significant reduction in mortality [hazard ratio 0.78 (95% CI 0.45-1.35, p = 0.37)] and composite outcome of mortality and new onset stroke [hazard ratio 0.86 (95% CI 0.60-1.24, p = 0.43)] in aspirin group as compared to placebo. However, aspirin as compared to placebo significantly reduced new onset stroke [hazard ratio of 0.51 (95% CI 0.29-0.87, p = 0.01)]. INTERPRETATION: We did not find significant reduction in mortality and composite outcome (mortality and new onset stroke) with aspirin as compared to placebo but there was significant reduction in new onset stroke in aspirin group as compared to placebo with Number Needed to Treat (NNT) = 10, which might be of clinical importance since stroke is responsible for high mortality and morbidity in these subset of patients. However, a large well conducted randomized controlled trial is required to put more light on the available evidence.

Topical fluoride-antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries: a systematic review and meta-analysis.

PURPOSE: To compare the effectiveness of topical fluoride-antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries among 1- to 16-year-old children. METHODS: PubMed, EbscoHost, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched for randomised controlled trials. The trials should have assessed the caries-preventive effectiveness of topical fluoride-antibacterial agent (Povidone Iodine/Chlorhexidine/Xylitol/Triclosan/Cetylpyridinium Chloride) combined therapy versus topical fluoride monotherapy among children. Out of 3475 records that were screened, full text of 41 articles was assessed for potential inclusion. Sixteen trials that fulfilled the eligibility criteria were subjected to qualitative synthesis. The risk of bias was assessed using the Cochrane Collaboration's tool. Continuous data from nine trials were pooled using Inverse Variance test in meta-analysis function of Review Manager (version 5.4). GRADE approach was used to analyse the certainty of evidence. Statistical heterogeneity was quantified using the I2 statistic. A p-value of < 0.05 was considered as statistically significant. RESULTS: With respect to the caries increment, combined therapy showed superior caries-preventive effectiveness than topical fluoride monotherapy [SMD - 0.12, 95% CI (- 0.2 to - 0.04), p = 0.004; (I2 = 20%, p = 0.29)]. No significant difference was noted between the two groups for the post-intervention salivary S mutans count [SMD - 0.11, 95% CI (- 0.33 to 0.1), p = 0.3; (I2 = 0%, p = 0.77)]. CONCLUSION: The pooled analysis indicates towards an added benefit of topical fluoride-antibacterial agent combined therapy over topical fluoride monotherapy in preventing dental caries incidence among children. However, the results may be interpreted with caution since the evidence generated is of low certainty and is driven by two studies on Xylitol, thus it demands further good quality trials.

Antibiotic stewardship in a tertiary care hospital of a developing country: establishment of a system and its application in a unit-GASP Initiative.

PURPOSE: Despite the proven benefits of antimicrobial stewardship, models for executing the same in the developing countries are sparse. The present study highlights the approaches undertaken by our group in initiating one such program in a public sector tertiary level health care setting of a developing country. METHODS: The study focussed on development of a system after evaluation of existing issues and case study of implementation of the program in a unit within the hospital. The system building exercise included (1) development of generic data capture form for prospective audit and feedback; (2) development of an electronic system for data capture; (3) identification of key intervention points for strategy decision for stewardship in a particular unit; (4) application of the stewardship method and (5) evaluation of outcomes. RESULTS: A digital system for prospective audit was constructed after a background study. In the study unit, there was a significant decline in double anaerobic coverage. There was a significant decline in the average number of antimicrobials used per patients and a decrease in Defined Daily Dose of designated antimicrobials was noted. Additionally, there was an increase in the use of optimized doses. CONCLUSION: A system for undertaking antimicrobial stewardship with a mechanism for prospective audit was put in place. The system may be adopted by other public sector hospitals of the developing country.

Fixed-dose combinations of antimicrobials: A need for special attention.

OBJECTIVE: To highlight the issue of freely available fixed-dose combinations (FDCs) of antimicrobials. METHODS: A critique of two such antimicrobial FDCs was undertaken wherein the following aspects were assessed - rational and regulatory issues and justification for clinical use. Available in vitro, in vivo (animals and humans) evidence from published literature was analysed. CONCLUSIONS: There are several inadequately addressed aspects of the considered FDCs which are available in Indian market. In view of the growing problem of antimicrobial resistance, this issue must get the required attention.

Hydroxychloroquine's Efficacy as an Antiplatelet Agent Study in Healthy Volunteers: A Proof of Concept Study.

BACKGROUND: With the inflammatory model of atherosclerosis taking center stage, anti-inflammatory drugs hold a promising place in the therapy of cardiovascular disease (CVD). Recent studies showed that hydroxychloroquine (HCQ) was protective against thrombovascular events in lupus erythematosus and traditional cardiovascular risk factors in patients with rheumatoid arthritis. Some preliminary experimental data have shown that it may prevent platelet activation too. OBJECTIVE: To evaluate the antiplatelet activity of HCQ when given alone and in combination with aspirin (ASA) and compare it with ASA alone and ASA plus clopidogrel (CLOP) in healthy human volunteers. METHODS: In part 1 of the study, 8 volunteers were given HCQ for 7 days. In part 2, 12 volunteers were randomly assigned in a 1:1:1 ratio to the 3 groups in which 2 of the 3 treatments, ASA, ASA plus CLOP, and ASA plus HCQ, were given in the 2 treatment periods separated by a 14-day washout period using the incomplete block design. Inhibition of platelet aggregation (IPA) was measured by light transmission aggregometry. RESULTS: When arachidonic acid (AA) was used as agonist, HCQ given alone showed a significant reduction in platelet aggregation (11.0% ± 4.2%, P = .03). The IPA was significantly increased when ASA plus HCQ was compared with ASA alone (31.2% ± 8.1%, P = .002). This synergistic effect was not seen with adenosine diphosphate and collagen as agonists. Levels of serum 11-dehydrothromboxane B2, a stable marker of thromboxane A2 production, were not significantly different between the groups. There was also a significant decrease in fibrinogen and erythrocyte sedimentation rate values when HCQ was used alone or in combination with ASA. CONCLUSION: This study suggests that HCQ has antiplatelet properties possibly through the AA pathway (downstream to thromboxane A2 production). With possible additional beneficial effects over the traditional CVD risk factors, larger studies in the future might explore HCQ's potential as an antiplatelet agent.

Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug.

Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T 1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85 ± 1.94 h, 13.77 ± 2.05 h, and 878.74 ± 133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

Development of tool for the assessment of comprehension of informed consent form in healthy volunteers participating in first-in-human studies.

Informed consent is a process that involves providing all pertinent study information to the potential study participant. The information imparted in the form gives all such information as would enable a potential participant to come to a decision regarding his/her participation in the study. Various study related aspects are outlined in the participant information leaflet including the background of the study, the benefits and risks, treatment alternatives; the methodology of the study, follow up schedules, confidentiality of the data, compensations and remunerations and right to not participate or withdraw from the study. We have continued a similar exercise for a phase I, first-in-human study, conducted by our center. Here, the volunteers were asked certain questions pertaining to the trial background, design, patients' rights and miscellaneous categories. They were then assessed and the scores compared to come up with certain conclusions. The median (range) for the entire comprehension score was calculated and statistically analyzed on various aspects. Readability of the ease of reading of the consent form was also analyzed on a Flesch-Kinkaid reading scale. A total of 69 volunteers were screened out of which 50 were enrolled in the study. The median (range) score was 27 (19 to 33) and the mean (S.D.) score was 28.9 (3.1). The maximum correct responses were observed for the questions falling under the volunteers' rights category. The Flesch reading ease score was 54 and the Flesch-Kincaid Grade level score was 9.8. Investigators may be encouraged to incorporate such tools in their informed consent process.

Evaluation of the ability of clinical research participants to comprehend informed consent form.

BACKGROUND: The comprehension of informed consent is an integral part of clinical trials. Though India is rapidly becoming a hub of clinical trials very few studies have dealt with the issue of comprehension of informed consent by the patients participating in these trials. METHODS: Patients who were invited to participate in a phase 3 multicentric trial of a novel lipid lowering agent were evaluated for comprehension score. The participants were explained about the structured consent form which included the question on background details for the study, design of the study, rights of the patients and miscellaneous aspects pertinent to the clinical trial. The questionnaire comprised of 24 items and each correct answer was assigned a score of 1. Total comprehension score (CS) was obtained by summing all the scores. RESULTS: Participants were from diverse socio economic and educational backgrounds. The mean +/- SD CS achieved by the participants was 13.4 +/- 2.9; median 14(6 to 20). The highest correct responses were obtained for questions on background details (38%). For most of the categories the mean CS was more than 50%. Aspects related to design were mostly difficult to comprehend. No significant difference in the CS was noted between participants from different educational and socioeconomic groups. 8 patients refused to give consent, fear of adverse drug reactions (n = 3) and inability to follow up (n = 5) were the reasons cited by the patients. CONCLUSION: In conclusion, CS of patients in trials conducted in developing countries can be reasonably good if the investigators explain the consent form in simple language to the participants and CS is not related to the educational status of the participants. Moreover, though a larger majority of patients agree to participate after knowing study details, some patients exercise their right to refuse.

Sildenafil for pulmonary hypertension: need for evidence generation.

BACKGROUND: The present meta-analysis was conducted with the aim of comparing the usefulness of sildenafil for the management of pulmonary hypertension (PH). METHODS: A systematic electronic and manual search was conducted to retrieve all published and unpublished randomized clinical trials of sildenafil in PH. Pertinent data related to various outcomes were extracted. Sildenafil was planned for comparison with placebo, prostacyclin analogs and endothelin receptor antagonists. For continuous data weighted mean difference was used while fixed or random effects models were used for dichotomous data. Revman (Version 4.2) was used for all calculations. RESULTS: Five studies with a total of 190 patients were included in the final analysis. As compared to placebo sildenafil showed a significant improvement in 6-min walk test (68.90 (95% CI 31.14 - 106.65), p = 0.0003), mean pulmonary artery pressure (-13.04 (95% CI - 25.94 to -0.15), p = 0.05), mean cardiac index (0.39 (95% CI 0.24 - 0.54), p < 0.00001), mean Borg dyspnea score (-1.23 (95% CI -1.36 to -1.10), p < 0.00001), mean pulmonary vascular resistance (-171 (95% CI -300 to -30.90), p = 0.02), improvement in functional class (6.48 (95% CI 2.74 - 15.33), p < 0.001) and a nonsignificant change in mean right atrial pressure and clinical worsening. No study satisfied inclusion criteria for comparison with prostacyclin analogs. In comparison with bosentan, sildenafil did not show a significant difference for any of the clinical outcomes of concern. CONCLUSION: In conclusion, sildenafil was shown to produce a significant improvement in functional and clinical outcomes as compared to placebo. There was no significant difference between sildenafil and bosentan for the study outcomes. There is a definite need for conducting adequately powered randomized controlled trials of sildenafil comparing it to placebo and also to other treatments approved for use in PH.

A meta-analysis to evaluate the efficacy of statins in children with familial hypercholesterolemia.

This meta-analysis was conducted to evaluate the effect of statins on the lipid profile in pediatric and adolescent patients with familial hypercholesterolemia (FH). Randomized, double-blind, controlled trials comparing statins with placebo were identified through electronic and manual search; percent reductions from baseline were calculated for various lipid parameters. Standardized mean differences (effect size) with 95% confidence interval (CI) were calculated for each study and pooled effect size was calculated. A total of 6 studies were included in the meta-analysis. As compared to placebo, statins caused a significant decrease in total cholesterol (TC) [-3.11% (95% CI -3.46 to -2.99)], low-density lipoprotein (LDL) [-4.01% (95% CI -4.27 to -3.81)], triglyceride (TG) [-1.41 (95% CI -1.66 to -1.26)] and a significant increase in high-density lipoprotein (HDL) [1.12 (95% CI 0.73 1.13)]. In conclusion, statins were shown to have good efficacy for the treatment of FH in children.

A randomized controlled clinical trial to evaluate the efficacy, safety, cost-effectiveness and effect on PAI-1 levels of the three low-molecular-weight heparins--enoxaparin, nadroparin and dalteparin. The ESCAPe-END study.

BACKGROUND: Comparative data for efficacy and safety between various low-molecular-weight heparins (LMWHs) in patients with unstable angina is not available. The present study was conducted to compare the efficacy, safety, cost-effectiveness and effects on plasminogen activator inhibitor-1 (PAI-1) levels of three LMWHs--enoxaparin, nadroparin and dalteparin. METHODS: The study was a prospective, randomized, comparative, open with blinded endpoints (PROBE design) assessment with a 30-day follow-up. The primary endpoint of efficacy was a composite of cardiovascular death, myocardial infarction, recurrent angina and need for intervention. Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio. Plasma PAI-1 levels were estimated by ELISA. RESULTS: A total of 150 patients were available for intention-to-treat analysis. There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups. The secondary endpoint of silent ischemia was also not significantly different. Adverse events were similar in the three groups. The PAI-1 levels were not significantly different in the three groups. The total cost of treatment in the three groups was similar. CONCLUSION: Any of the three LMWHs evaluated in this study were similar with respect to efficacy, safety, PAI-1 levels and cost-effectiveness.

Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial--the GONIP Trial.

BACKGROUND: Gabapentin and nortriptyline have not been compared in a randomized trial in post-herpetic neuralgia (PHN). The present study was, therefore, undertaken to determine their comparative efficacy and tolerability in the treatment of post-herpetic neuralgia. PATIENTS AND METHODS: The study was a randomized, double-blind, parallel-group trial of 9 weeks duration. Adult PHN patients with history of > 8 weeks of PHN pain after healing of rash, a pain intensity of at least 40 mm on a 100 mm visual analog scale at screening and at randomization, and average pain score of at least 4 on the Likert scale during the baseline week were included in the study. Gabapentin and nortriptyline were given in incremental doses at 2-weekly intervals till a maximum tolerated dose was obtained. The primary efficacy parameter was change in pain score (11-point Likert scale) from baseline to the end of the study period. RESULTS: 70 patients were available for intention-to-treat analysis. The average pain scores on the Likert scale were significantly reduced at the end of study in both the treatment groups with 47.6% and 42.8% reduction in pain scores in nortriptyline and gabapentin groups, respectively. Patients showed significant improvement in sleep scores in both the treatment groups nortriptyline (46.0%) and gabapentin (52.0%). The VAS and the SF-MPQ scores for pain were significantly reduced in both the groups. Gabapentin was, however, better tolerated as compared to nortriptyline. CONCLUSION: Gabapentin was shown to be equally efficacious but was better tolerated compared to nortriptyline and can be considered a suitable alternative for the treatment of PHN.

A meta-analysis of trials comparing Cypher and Taxus stents in patients with obstructive coronary artery disease.

AIMS: Drug-eluting stents have been shown to be superior to bare metal stents in reducing restenosis rates. Recently head-to-head trials comparing sirolimus-eluting stents and paclitaxel-eluting stents have been reported. An early combined analysis of these comparative trials is needed. The present meta-analysis was carried out to compare the effects of sirolimus-eluting stents with paclitaxel-eluting stents on the restenosis rate, major adverse cardiac events and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Electronic (Medline, Cochrane and Embase) and manual search (Index Medicus and cross references of retrieved articles) were carried out for all the relevant articles up till March 2005. Only randomized trials with adequate data for calculation of odds ratio for restenosis rates and major adverse cardiac events using the method of DerSimonian & Laird and standardized mean difference for late loss of arterial lumen diameter were included. RESULTS: Four studies were found to be eligible for inclusion in the meta-analysis. Restenosis rate and late loss of arterial lumen diameter were significantly reduced by sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.598, 95% CI 0.400, 0.893, pooled mean difference -0.414, 95% CI -0.492, 0.336, respectively). The incidence of major adverse cardiac events was less with sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.727, 95% CI 0.518-1.018) but the results were not statistically significant. CONCLUSIONS: Sirolimus-eluting stents are superior to paclitaxel-eluting stents in decreasing restenosis rate and late loss of arterial lumen diameter. However, no statistically significant difference in major adverse cardiac events was noted between the two stents.

Study design and rationale of a mock phase I trial as an educational tool for clinical pharmacology residents.

OBJECTIVE: To invite comments and suggestions from the phase I trialists, the world over, on the design and rationale provided by us for conducting a mock phase I trial for training clinical pharmacology residents. METHODS: The trial will be conducted by clinical pharmacology residents of the Post Graduate Institute of Medical Education and Research. After a thorough evaluation of Preclinical toxicity data of a pharmaceutical product provided by a dummy pharmaceutical firm, a randomized, double-blind, placebo controlled, parallel group design with dose escalation of the product will be carried out. A single dose administration will be followed by monitoring the participants for 24 h and again at one week. After obtaining results of the previous group, the next higher dose will be administered. Evaluation of the learners will be done by two independent teachers who will mark them for actual conduct of the study and writing a report of the study. Subsequently, we will try to publish the results of the mock trial and invite further comments. CONCLUSIONS: This trial designed primarily for training purposes will be instrumental in equipping the residents with the expertise for conducting phase I trials.

What clinical pharmacology means to us.

Clinical Pharmacology is a specialty with many attributes and our association with the subject has allowed us to acquire, apply and disseminate myriad aspects of research and practice. Though clinical pharmacologists are conspicuous by virtue of their small number, recent years have shown a growing need for the course. In the review below we navigate through several aspects of the subject as we encountered them from time to time. From critical appraisal of literature, to application of knowledge of drugs, to clinical practice; moving on to clinical and basic research, to drug development process, to policy making - these are but a few of the many fields which constitute the scope of clinical pharmacology. The importance of the subject lies in allowing a trainee to develop a broad overview of the entire process, from drug generation to drug distribution to drug utilization, a process meant for the greater common goal of better health for all. We foresee a bright future for the subject though with a slight skepticism thrown in. In the present article, we make use of personal experiences and reference from literature to help you get a broad view of what clinical pharmacology means to us.

Comparative gastrointestinal toxicity of selective cyclooxygenase (COX-2) inhibitors.

Cyclooxygenase (COX-2) inhibitors were developed with the hope that they will cause fewer gastrointestinal adverse effects. Ability of selective as well as nonselective COX inhibitors to alter ischemia-reperfusion induced damage of gastric mucosa and hapten-induced colitis in rats has been compared. Celecoxib (10, 20 and 40 mg/kg(-l)) was significantly more potent at aggravating ischemia-reperfusion injury as compared to nimesulide. Similarly, celecoxib was found to maximally potentiate TNBS-induced colitis, followed by nimesulide and indomethacin. Celecoxib at its highest dose produced maximum deep histological injury. This paradoxic ulcer and colitis aggravating effect of selective COX-2 inhibitors may be explained by suppression of protective prostaglandins generated as a consequence of COX-2 induction in inflammatory states.

A meta-analysis of clinical trials of paclitaxel- and sirolimus-eluting stents in patients with obstructive coronary artery disease.

AIM: This meta-analysis was conducted to compare the effects of drug (paclitaxel and sirolimus)-eluting stents with bare metal stents on major adverse cardiac events, restenosis rates and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Randomized, controlled clinical trials comparing sirolimus- and paclitaxel-eluting stents with bare metal stents were identified through electronic and manual search. Fixed effects method of Mantel-Haenszel and random effects method of DerSimonian and Laird were used for computing the pooled odds ratio (OR) and 95% confidence intervals (CI) for major adverse cardiac events and restenosis rates. Standardized mean difference with 95% CI was calculated for late-loss of arterial lumen diameter. RESULTS: A total of 13 studies were included in the meta-analysis. As compared with bare metal stents, the use of sirolimus- and paclitaxel-eluting stents significantly reduced the major adverse cardiac events (pooled OR 0.35; 95% CI 0.24-0.50), restenosis rates (pooled OR 0.27; 95% CI 0.15-0.47), and late loss of arterial lumen diameter (mean difference 0.57 mm, 95% CI 0.49-0.68). CONCLUSION: Paclitaxel- and sirolimus-eluting stents significantly reduced the incidence of major adverse cardiac events, restenosis rates, and late loss of arterial lumen diameter as compared with bare metal stents.

A comparison of observational studies and controlled trials of heparin in ulcerative colitis.

OBJECTIVES: To compare the efficacy of heparin in ulcerative colitis (UC) as demonstrated in observational studies and controlled clinical trials. INTRODUCTION: Ulcerative colitis (UC) is a chronic condition with a relapsing and remitting course. Several studies have been conducted (observational and controlled clinical trials) to test the usefulness of heparin in this condition but the results of these studies are variable. Some studies demonstrate efficacy while others do not. METHODS: We pooled the results of observational studies and clinical trials separately in order to compare the results of observational studies and clinical trials using meta-analysis. With the aid of Medline and a manual search in Index Medicus and cross-references of articles published up to July 2003, we identified studies designed to evaluate the effects of heparin on UC. The pooled cure rate in observational studies was calculated. RESULTS: The results of controlled clinical trials evaluated using meta-analysis showed that the pooled cure rate for observational studies was 87.7% (range 80 - 100). The odds ratio for the controlled trial was 0.34 (95% CI 0.08 - 1.49) using a random effects model and 0.21 (95% CI 0.06 - 1.38) using a fixed effects model. The results of meta-analysis demonstrate a non-significant effect of heparin in controlled clinical trials. CONCLUSION: The findings of the clinical trials differ markedly from observational studies and indicate a lack of efficacy of heparin in patients with ulcerative colitis.