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The Cochrane Database of Systematic... Apr 2012During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed.
OBJECTIVES
To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children.
SEARCH METHODS
For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies.
DATA COLLECTION AND ANALYSIS
Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir.
MAIN RESULTS
Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar.
AUTHORS' CONCLUSIONS
Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.
Topics: Antiviral Agents; Child; Child, Preschool; Enzyme Inhibitors; Guanidines; Humans; Infant; Influenza, Human; Neuraminidase; Oseltamivir; Pyrans; Randomized Controlled Trials as Topic; Sialic Acids; Zanamivir
PubMed: 22513907
DOI: 10.1002/14651858.CD002744.pub4 -
The Cochrane Database of Systematic... Jan 2012During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed.
OBJECTIVES
To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children.
SEARCH METHODS
For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies.
DATA COLLECTION AND ANALYSIS
Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir.
MAIN RESULTS
Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar.
AUTHORS' CONCLUSIONS
Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. Oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.
Topics: Acetamides; Antiviral Agents; Child; Enzyme Inhibitors; Guanidines; Humans; Influenza, Human; Neuraminidase; Oseltamivir; Pyrans; Randomized Controlled Trials as Topic; Sialic Acids; Zanamivir
PubMed: 22258949
DOI: 10.1002/14651858.CD002744.pub3 -
Addiction (Abingdon, England) Nov 2011To assess the effectiveness of methamphetamine precursor regulations in reducing illicit methamphetamine supply and use. (Review)
Review
AIMS
To assess the effectiveness of methamphetamine precursor regulations in reducing illicit methamphetamine supply and use.
METHODS
A systematic review of 12 databases was used to identify studies that had evaluated the impact of methamphetamine precursor regulations on methamphetamine supply and/or use. The guidelines of the Effective Practice and Organization of Care Group (EPOC) of The Cochrane Collaboration were used to determine which study designs were included and assess their quality.
RESULTS
Ten studies met the inclusion criteria. These studies evaluated 15 interventions (13 regulations and two related interdiction efforts), all of which were located in North America. Interventions had consistent impacts across various indicators of methamphetamine supply and use. Seven of the 15 interventions produced reductions in methamphetamine indicators (ranging from 12% to 77%). Two of the largest impacts were seen following interdiction efforts, involving the closure of rogue pharmaceutical companies. There was no evidence of a shift into other types of drug use, or injecting use, although the impact on the synthetic drug market was not examined. Null effects were related largely to the existence of alternative sources of precursor chemicals or the availability of imported methamphetamine.
CONCLUSIONS
Methamphetamine precursor regulations can reduce indicators of methamphetamine supply and use. Further research is needed to determine whether regulations can be effective outside North America, particularly in developing countries, and what impact they have on the broader synthetic drug market. Improved data on precursor diversion are needed to facilitate the evaluation of precursor regulations.
Topics: Amphetamine-Related Disorders; Central Nervous System Stimulants; Commerce; Designer Drugs; Developing Countries; Drug and Narcotic Control; Humans; Illicit Drugs; Law Enforcement; Methamphetamine; Nasal Decongestants; North America; Prodrugs; Program Evaluation; Pseudoephedrine
PubMed: 21895829
DOI: 10.1111/j.1360-0443.2011.03582.x -
Expert Review of Pharmacoeconomics &... Apr 2010Capecitabine, an oral prodrug of 5-fluorouracil, is indicated for adjuvant treatment in patients with Dukes' C colon cancer and for subsequent lines in metastatic... (Review)
Review
Capecitabine, an oral prodrug of 5-fluorouracil, is indicated for adjuvant treatment in patients with Dukes' C colon cancer and for subsequent lines in metastatic colorectal cancer. The aim of this article is to review the literature on the economics of capecitabine for the treatment of colon cancer. A systematic review was conducted to search for articles published from January 2003 to December 2009 that met the inclusion criteria. For abstracts that were considered acceptable, full-text articles were then reviewed. Of the 42 potential studies that were identified, 13 original studies (16 publications) met the inclusion criteria. To date, the economic evaluation literature has consistently projected or found that capecitabine is not only a cost-effective treatment for adjuvant or for metastatic colorectal cancer (i.e., providing good value for money) but, furthermore, would actually be cost saving in the majority of country settings.
Topics: Antimetabolites, Antineoplastic; Capecitabine; Chemotherapy, Adjuvant; Colorectal Neoplasms; Cost Savings; Cost-Benefit Analysis; Deoxycytidine; Fluorouracil; Health Care Costs; Humans; Neoplasm Metastasis; Prodrugs
PubMed: 20384557
DOI: 10.1586/erp.10.12 -
Drugs of Today (Barcelona, Spain : 1998) Feb 2010Cyclooxygenase (COX) enzymes mediate prostaglandin generation. COX-1 is expressed in all cells, producing prostaglandins that maintain cellular homeostasis, and COX-2 is... (Review)
Review
Cyclooxygenase (COX) enzymes mediate prostaglandin generation. COX-1 is expressed in all cells, producing prostaglandins that maintain cellular homeostasis, and COX-2 is an inducible enzyme that generates inflammatory prostaglandins at sites of inflammation and healing. Nonsteroidal antiinflammatory drugs (NSAIDs) that nonselectively inhibit COX-1 and COX-2 continue to be an important option for the management of pain. However, despite the potential advantages of NSAIDs, including their opioid-sparing effect and reduced opioid-related side effects, improved analgesia, and attenuation of the inflammatory pain response, several side effects limit their use. NSAIDs predispose to ulcer formation and upper gastrointestinal bleeding, impaired coagulation, cardiovascular effects and renal dysfunction. Selective cyclooxygenase-2 (COX-2) inhibitors were designed based on the hypothesis that selective inhibition of the COX-2 isoform should reduce pain and inflammation without compromising the integrity of the gastric mucosa. Celecoxib and parecoxib are two COX-2 inhibitors (coxibs) that are approved for the relief of acute postoperative pain and symptoms of chronic inflammatory conditions such as osteoarthritis and rheumatoid arthritis. They have similar pharmacological properties but a slightly improved gastrointestinal safety profile compared with traditional NSAIDs. Celecoxib is an orally administered coxib. Agents such as celecoxib, which are highly COX-2 specific and have shown excellent efficacy in relieving inflammation and associated pain, unfortunately exhibit only modest aqueous solubility, thus restricting dosing options. Parecoxib is the sulfonamide-based prodrug of valdecoxib and is the only parenterally administered coxib available to date. There is no evidence demonstrating any greater degree of pain relief between these two coxibs. However, parenteral preparations may be especially useful in the immediate postoperative period, when patients are unable to take oral medication or are experiencing nausea and vomiting.
Topics: Animals; Celecoxib; Cyclooxygenase 2 Inhibitors; Drug Administration Routes; Evidence-Based Medicine; Humans; Inflammation; Isoxazoles; Pain; Pain Measurement; Pyrazoles; Structure-Activity Relationship; Sulfonamides; Treatment Outcome
PubMed: 20224826
DOI: No ID Found -
Expert Opinion on Drug Metabolism &... Oct 20095-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the... (Review)
Review
BACKGROUND
5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC.
OBJECTIVE
To summarize current data on balsalazide and to discuss its impact on management of UC.
METHODS
A systematic review of published literature was performed on PubMed using the search terms 'Balsalazide' and 'Colazal(TM)'. The Cochrane database was also reviewed.
RESULTS
Balsalzide, a 5-ASA prodrug, ulilizes azoreduction by colonic bacteria to achieve a sustained release of active 5-ASA throughout the colon. A recent clinical trial has demonstrated balsalazide 6.7 g/day to be superior to placebo in inducing remission in symptomatic UC. The drug is well tolerated with a safety profile comparable to other oral 5-ASA agents. The current data suggests that symptomatic remission occurs with both greater swiftness and greater frequency when compared with mesalamine.
CONCLUSION
Balsalazide is approved for the treatment of mild-to-moderate active UC. It is efficacious for the induction of remission in mild to moderate UC and has a favorable safety profile, with the added advantages of greater efficacy of remission induction and rapidity of onset.
Topics: Clinical Trials as Topic; Colitis, Ulcerative; Delayed-Action Preparations; Gastrointestinal Agents; Humans; Mesalamine; Phenylhydrazines; Prodrugs; Remission Induction
PubMed: 19743890
DOI: 10.1517/17425250903206996 -
European Heart Journal Aug 2009Currently, clopidogrel is recommended for treatment of patients with acute coronary syndrome and/or percutaneous coronary intervention. However, the delayed onset of the... (Review)
Review
Currently, clopidogrel is recommended for treatment of patients with acute coronary syndrome and/or percutaneous coronary intervention. However, the delayed onset of the effect and the occurrence of poor platelet inhibition responders with clopidogrel as well as non-compliance to dual antiplatelet treatment are associated with a raised risk of stent thrombosis. The molecular target of the active metabolite of clopidogrel and several emerging antiplatelet treatments is the P2Y(12) receptor, which is the main platelet receptor responsible for ADP-induced platelet aggregation. Active metabolites of the thienopyridine prodrugs (ticlopidine, clopidogrel, and prasugrel) covalently bind to the P2Y(12) receptor and are irreversible, indirect platelet inhibitors. The newer, direct-acting P2Y(12) inhibitors (cangrelor and ticagrelor) change the conformation of the P2Y(12) receptor, resulting in reversible, concentration dependent inhibition of the receptor. An understanding of the similarities and differences in the properties and mechanisms of action of these new inhibitors compared with clopidogrel is needed in order to optimize the development and use of these agents in clinical practice. The objectives of this systematic review are to summarize the pharmacokinetics, pharmacodynamics, and pharmacogenetics of the different P2Y(12) inhibitors and to discuss the clinical implications for treatment of patients.
Topics: Acute Coronary Syndrome; Clopidogrel; Cytochrome P-450 Enzyme System; Humans; Piperazines; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Pyridines; Thiophenes; Ticlopidine
PubMed: 19633016
DOI: 10.1093/eurheartj/ehp296 -
The Cochrane Database of Systematic... Jul 2009Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic... (Review)
Review
BACKGROUND
Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral aceclofenac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
OBJECTIVES
To assess the efficacy of single dose oral aceclofenac in acute postoperative pain, and any associated adverse events.
SEARCH STRATEGY
We searched The Cochrane Library (Issue 1, 2009), MEDLINE via Ovid (1966 to March 2009); EMBASE via Ovid (1980 to March 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of oral aceclofenac for relief of acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
MAIN RESULTS
Searches identified only one study (217 participants total), which used oral aceclofenac 150 mg in patients with established postoperative pain. Aceclofenac 150 mg could not be distinguished from placebo, though ibuprofen 400 mg was distinguished from placebo.
AUTHORS' CONCLUSIONS
In the absence of evidence of efficacy for oral aceclofenac in acute postoperative pain (at least at 150 mg single dose), its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies are lacking, use in other indications should be evaluated carefully. Given the large number of effective drugs available in this and similar classes of analgesics, there is no urgent research agenda required to demonstrate the effective dose of aceclofenac in acute postoperative pain.
Topics: Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Pain, Postoperative
PubMed: 19588436
DOI: 10.1002/14651858.CD007588.pub2 -
Orvosi Hetilap Mar 20095-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond... (Review)
Review
5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Drug Administration Schedule; Humans; Medication Adherence; Mesalamine; Remission Induction; Severity of Illness Index
PubMed: 19228568
DOI: 10.1556/OH.2009.28555 -
The Cochrane Database of Systematic... Jan 2009The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta-analysis was performed to evaluate the efficacy of these agents for the maintenance of remission of quiescent Crohn's disease.
OBJECTIVES
To assess the efficacy of azathioprine and 6-mercaptopurine for maintenance of remission in quiescent Crohn's disease.
SEARCH STRATEGY
Pertinent studies were selected using the MEDLINE data base (1966-May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease register, as well as abstracts from major gastrointestinal research meetings and references from published articles and review. This search strategy was updated (1998-May 2008) using the MEDLINE, EMBASE and International Pharmaceutical Abstracts databases, the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register.
SELECTION CRITERIA
Randomized, double-blind, placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with quiescent Crohn's disease.
DATA COLLECTION AND ANALYSIS
Data were extracted by three independent observers (EP, MC, LRS) based on the intention to treat principle. Peto odds ratios and 95% confidence intervals for maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined.
MAIN RESULTS
Seven trials of azathioprine therapy and one of 6-mercaptopurine were included in the review. Azathioprine and 6-mercaptopurine had a positive effect on maintaining remission. The Peto odds ratio (OR) for maintenance of remission with azathioprine was 2.32 (95% CI 1.55 to 3.49) with a NNT of 6. The Peto OR for maintenance of remission with 6-mercaptopurine was 3.32 (95% CI 1.40 to 7.87) with a of 4. Higher doses of azathioprine improved response. A steroid sparing effect with azathioprine was noted, with a Peto OR of 5.22 (95% CI 1.06 to 25.68) and NNT of 3 for quiescent disease. Withdrawals due to adverse events were more common in patients treated with azathioprine (Peto OR 3.74; 95% CI 1.48 to 9.45, NNH = 20) than with placebo.
AUTHORS' CONCLUSIONS
Azathioprine and 6-mercaptopurine are more effective than placebo for maintenance of remission in Crohn's disease. Higher response rates were obtained with azathioprine than 6-mercaptopurine. However, the one study evaluating 6-mercaptopurine used a relatively low dose of the drug. Future studies should look at the effect of higher doses of 6-mercaptopurine. There is weak evidence for a steroid sparing effect with azathioprine treatment.
Topics: Azathioprine; Crohn Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Prodrugs; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 19160175
DOI: 10.1002/14651858.CD000067.pub2