Efficacy and tolerability of renzapride in irritable bowel syndrome: a meta-analysis of randomized,controlled clinical trials including 2528 patients

Introduction

By targeting different subtypes of 5-hydroxytryptamine (5HT) receptors in the gastrointestinal (GI) tract, several drugs have been introduced for the management of irritable bowel syndrome (IBS). Renzapride is a full agonist for 5HT4 receptor and an antagonist to 5HT2b and 5HT3 receptors which is thought a promising therapeutic agent for constipation predominant IBS (C-IBS) patients due to its accelerating effect on the GI tract. In this meta-analysis, our aim was to evaluate the efficacy and tolerability of renzapride in the management of IBS.

Material and methods

A search was done from 1992 to February 2013 for placebo-controlled trials that investigated the efficacy of renzapride in IBS.

Results

Relative risk (RR) for clinical efficacy in IBS patients treated for 5 weeks or less comparing renzapride to placebo was 1.07 (95% CI = 0.89–1.29, p = 0.38). This value for IBS patients treated for more than 5 weeks was 1.04 (95% CI = 0.78–1.239, p = 0.77). The RR for clinical efficacy in IBS patients treated with renzapride (4 mg) for 5 weeks or less and more than 5 weeks in comparison to placebo was 1.2 (95% CI = 0.97–1.48, p = 0.1) and 1.16 (95% CI = 0.98–1.37, p = 0.08), respectively, which were statistically non-significant but clinically important. The analysis of tolerability demonstrated that amongst different reported adverse effects, renzapride caused diarrhea more than placebo (RR = 1.61 with a 95% CI = 1.16–2.24, p = 0.004). The RR for withdrawals from renzapride compared to placebo was 1.58 (95% CI = 1.26–2.07, p = 0.0007).

Conclusions

Renzapride is not superior to placebo in relieving IBS symptoms and causes significant incidences of diarrhea and drop-outs due to adverse effects in treated patients vs. placebo. Thus, this medicine might be a cost burden to patients without providing good effectiveness.     

Atazanavir / ritonavir versus Lopinavir / ritonavir-based combined antiretroviral therapy (cART) for HIV-1 infection: a systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis was conducted to evaluate the safety and effectiveness of Atazanavir/ritonavir over lopinavir/ritonavir in human immunodeficiency virus-1 (HIV-1) infection.MethodsClinical trials with a head-to-head comparison of atazanavir/ritonavir and lopinavir/ritonavir in HIV-1 were included. Electronic databases: PubMed/Medline CENTRAL, Embase, Scopus, and Web of Science were searched. Viral suppression below 50 copies/ml at the longest follow-up period was the primary outcome measure. Grade 2–4 treatment-related adverse drug events, lipid profile changes and grade 3–4 bilirubin elevations were used as secondary outcome measures.ResultsA total of nine articles from seven trials with 1938 HIV-1 patients were included in the current study. Atazanavir/ritonavir has 13% lower overall risk of failure to suppress the virus level < 50 copies/ml than lopinavir/ritonavir in fixed effect model (pooled RR: 0.87; CI: 0.78, 0.96; P=0.006). The overall risk of hyperbilirubinemia is very high for atazanavir/ritonavir than lopinavir/ritonavir in the random effects model (pooled RR: 45.03; CI: 16.03, 126.47; P< 0.0001).ConclusionAtazanavir/ritonavir has a better viral suppression at lower risk of lipid abnormality than lopinavir/ritonavir. The risk and development of hyperbilirubinemia from atazanavir-based regimens should be taken into consideration both at the time of prescribing and patient follow-up.     

A meta-analysis on the efficacy and tolerability of natalizumab in relapsing multiple sclerosis

Introduction

Natalizumab is a new humanized monoclonal antibody used in multiple sclerosis (MS). The aim of this meta-analysis was to evaluate the efficacy and tolerability of this drug in relapsing MS. PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy and/or tolerability of natalizumab in MS. Data were collected from 1966 to 2008 (up to October).

Material and methods

The search terms were: “multiple sclerosis” or “MS” and “natalizumab”. “Mean change in Expanded Disability Status Scale (EDSS)”, “number of patients with at least one relapse”, and “number of patients with at least one new gadolinium (Gd)-enhancing lesion” were the key outcomes of interest for assessment of efficacy. “Any adverse events”, “serious adverse events”, “death”, and “withdrawal because of adverse events” were the key outcomes for tolerability. Among existing trials, four randomized placebo controlled clinical trials met our criteria and were included.

Results

Pooled relative risk for at least one relapse in four trials including all doses was 0.7, with a non-significant RR (95% CI: 0.42–1.17, p = 0. 17). Summary RR for at least one relapse in two trials in which doses of 3 mg/kg or 6 mg/kg or 300 mg every 4 weeks were administered gave a value of 0.5 asa significant RR (95% CI: 0.42–0.61, p < 0.0001). The summary RR for at least one new Gd-enhancing lesion was 0.22, a non-significant RR (95% CI: 0.05–1.01, p = 0.051). Three deaths were reported in the natalizumab group. Comparing adverse events between natalizumab and placebo yielded a non-significant RR of 0.99 (95% CI: 0.96–1.01, p = 0.34) for any adverse events (n = 3), and a significant RR of 0.39 (95% CI: 0.29–0.52, p < 0.0001) for serious adverse events (n = 2). The summary RR for withdrawal due to adverse events by natalizumab vs. placebo therapy between two trials was 1.43, a non-significant RR (95% CI: 0.68–3.02, p = 0.35).

Conclusions

It seems that using 3 or 6 mg/kg every 4 weeks is the best method of administration of natalizumab for preventing relapse and occurrence of new Gd-enhancing lesions. The current data on the efficacy and safety of natalizumab are insufficient to reach a convincing conclusion and thus further clinical trials are still needed.     

A system dynamics model for national drug policy

Background

Data modeling techniques can create a virtual world to analyze decision systems. National drug authorities can use such techniques to take care of their deficiencies in decision making processes. This study was designed to build a system dynamics model to simulate the effects of market mix variables (5 P’s) on the national drug policy (NDP) indicators including availability, affordability, quality, and rationality. This was aimed to investigate how to increase the rationality of decision making, evaluate different alternatives, reduce the costs and identify the system obstacles.System dynamics is a computer-based approach for analyzing and designing complex systems over time. In this study the cognitive casualty map was developed to make a concept about the system then the stock-flow model was set up based on the market demand and supply concept.

Results

The model demonstrates the interdependencies between the NDP variables through four cognitive maps. Some issues in availability, willingness to pay, rational use and quality of medicines are pointed in the model. The stock-flow diagram shows how the demand for a medicine is formed and how it is responded through NDP objectives. The effects of changing variables on the other NDP variables can be studied after running the stock-flow model.

Conclusion

The model can initiate a fundamental structure for analyzing NDP. The conceptual model made a cognitive map to show many causes’ and effects’ trees and reveals some relations between NDP variables that are usually forgotten in the medicines affairs. The model also provides an opportunity to be expanded with more details on a specific disease for better policy making about medication.     

Monitoring of National Drug Policy (NDP) and its standardized indicators; conformity to decisions of the national drug selecting committee in Iran

Background  

Pharmaceuticals have made an important contribution to global reductions in morbidity and mortality. To help save lives and improve health, it is important to be sure about equity to access to drugs, drug efficacy, quality and safety, and rational use of drugs, which are standardized National Drug Policy (NDP) objectives. NDP's indicators are useful to evaluate the pharmaceutical system performance in a country. Iran has adapted a National Drug List (NDL). Since management of drug supply in Iran takes place only for drugs that have been selected in NDL and this list is selected by the member of Iran Drug Selecting Committee (IDSC), thus evaluation of IDSC's decision making during last 5 years is an appropriate way to evaluate the implementation of drug supply system in the country.     

Use of proton pump inhibitors during pregnancy and rates of major malformations: a meta-analysis

Proton pump inhibitors are used to treat gastroesophageal reflux, a symptom common in pregnancy. The aim of this study was to systematically analyze the available data on the risk for malformations following use of these agents in the first trimester of pregnancy. Medline, EMBASE, published abstracts, and reference lists were searched for articles reporting on proton pump inhibitor use in pregnancy. Summary relative risks and 95% confidence intervals (95% CI) were calculated using the Mantel-Haenszel method. Five cohort studies met the inclusion criteria for this meta-analysis. With almost 600 exposed pregnancies, the overall relative risk was 1.18 with a 95%CI of 0.72–1.94. In conclusion, proton pump inhibitors do not present a major teratogenic risk when used in recommend doses. These data are reassuring for the countless patients who have used these agents in the early part of their pregnancies.     

Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials

BACKGROUND: Stimulated 5-hydroxytryptamine-3 (5-HT(3)) receptors promote intestinal motility, secretion, and sensation, effects that are related to the known pathophysiology of irritable bowel syndrome (IBS). A previous meta-analysis of 6 randomized controlled trials of the 5-HT(3)-receptor antagonist alosetron found that this agent was associated with global improvement in symptoms, pain, and discomfort in patients with IBS. OBJECTIVE: This was a meta-analysis of randomized, placebo-controlled trials that evaluated the efficacy and tolerability of alosetron for the management of IBS. It updated and expanded on the previous meta-analysis. METHODS: PubMed, EMBASE, SCOPUS, Web of Science, and the cochrane central Register of controlled Trials were searched from 1966 through September 2007 for placebo-controlled trials that examined the efficacy and tolerability of alosetron in the management of IBS. The search terms were alosetron, 5-HT, irritable bowel, functional bowel diseases, and irritable colon. No language restriction was applied. The data were analyzed in terms of 2 main outcomes: global improvement in IBS symptoms and adequate relief of IBS pain and discomfort. RESULTS: Eight multicenter, randomized, placebo-controlled, 12-week clinical trials met the criteria for inclusion in the meta-analysis. The studies included 4,170 patients with IBS (80% female) who were randomized to receive either alosetron or placebo. All patients met the Rome criteria for IBS, and all subtypes of IBS were represented. Most patients had diarrhea-predominant IBS; only 2.6% of patients had constipation-predominant IBS. In the 3 trials included in the analysis of global improvement in symptoms, alosetron was significantly more effective than placebo (relative risk [RR] = 1.60; 95% CI, 1.44-1.76; P <0.001). In the 6 trials included in the analysis of adequate relief of IBS pain and discomfort, there was also a significant difference in favor of alosetron (RR = 1.31; 95% CI, 1.20-1.43; P < 0.001). Analysis of adequate relief of IBS pain and discomfort by sex also indicated significant differences between alosetron and placebo in both sexes (female: RR = 1.34 [95% cI, 1.21-1.48]; male: RR = 1.23 [95% CI, 1.02-1.47]). The analysis of tolerability, which was based on data from 7 studies, found a significant difference between alosetron and placebo (RR = 1.19; 95% cI, 1.07-1.31; P<0.001). The only adverse events that occurred with a significantly higher incidence in those treated with alosetron compared with placebo were constipation in 8 trials (RR = 4.35; 95% CI, 3.01-6.26; P < 0.001) and abdominal pain and discomfort in 5 trials (RR = 1.96; 95% CI, 1.46-2.64; P < 0.001). In the alosetron group, there were 4 cases of ischemic colitis (0.16%) and 2 cases of serious complications of constipation (0.08%); neither of these was reported in the placebo group. Alosetron was not associated with any deaths. CONCLUSIONS: Alosetron was effective in these men and women with IBS. constipation was the most frequently reported adverse event associated with alosetron therapy. Ischemic colitis and serious complications of constipation were reported in a small number of patients treated with alosetron.     

On the Benefit of Probiotics in the Management of Pouchitis in Patients Underwent Ileal Pouch Anal Anastomosis: A Meta-analysis of Controlled Clinical Trials

The objective of this study was to evaluate and collect current evidence on the effect of probiotics in preventing pouchitis after restorative ileal pouch anal anastomosis (IPAA). The Pubmed, Medline, EMbase, CINAHL, Web of Science, and Scopus bibliographic, and Google Scholar databases were searched between 1966 and May 2007, and relevant controlled clinical trials were extracted, reviewed, and validated according to the study protocol. The outcome of interest was for pouchitis defined by a pouchitis disease activity index (PDAI) ≥7. Five randomized, placebo-controlled clinical trials were included in the meta-analysis. Pooling of the results from these trials yielded an odds ratio (OR) of 0.04 with a 95% CI of 0.01–0.14 (P < 0.0001) in the treatment group in comparison with the placebo group. In conclusion, the benefit of probiotics in the management of pouchitis after IPAA operation was confirmed by the meta-analysis.     

Do anti-tumor necrosis factors induce response and remission in patients with acute refractory Crohn's disease? A systematic meta-analysis of controlled clinical trials

To determine whether anti-tumor necrosis factors induce clinical response and remission in patients with Crohn's disease, PUBMED, OVID, and SCOPUS databases were searched for studies investigated the efficacy of anti-tumor necrosis factors on CD. Data were collected from 1966 to 2005 (up to 31 December). Types of outcome investigated were response (decrease in CDAI score >/=70 points) and remission (CDAI score 相似文献