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The Cochrane Database of Systematic... Nov 2016Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the... (Review)
Review
BACKGROUND
Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications.
OBJECTIVES
To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016.
SELECTION CRITERIA
We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach.
MAIN RESULTS
One study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.Persistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir.
AUTHORS' CONCLUSIONS
This review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.
Topics: Acyclovir; Antiviral Agents; Herpes Zoster Ophthalmicus; Humans; Immunocompetence; Randomized Controlled Trials as Topic; Valacyclovir; Valine
PubMed: 27841441
DOI: 10.1002/14651858.CD011503.pub2 -
The Cochrane Database of Systematic... 2000To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease. (Review)
Review
OBJECTIVES
To assess the effectiveness of azathioprine in maintaining remission of 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 Trials Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and reviews.
SELECTION CRITERIA
Five randomized, double-blind, placebo-controlled trials of azathioprine therapy were identified. Two of these trials consisted solely of patients with quiescent Crohn's disease. Three trials had multiple therapeutic arms for both induction of remission and maintenance of remission.
DATA COLLECTION AND ANALYSIS
Data were extracted by three independent observers (GRM, GF, LRS) based on the intention to treat principle. Peto odds ratios for the overall maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated, and from these, 95% confidence intervals were derived. 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
Azathioprine had a positive effect on maintaining remission. The Peto odds ratio for maintenance of remission was 2.16 (CI 1.35 - 3.47) with an NNT of 7. A higher dose improved response. A steroid sparing effect was noted, with a Peto odds ratio of 5.22 (CI 1.06 - 25.68) and NNT of 3 for quiescent disease. The Peto odds ratio for withdrawals due to adverse events was 4.36 (CI 1.63 - 11.67), the NNH (Number Needed to Harm) was 19.
REVIEWER'S CONCLUSIONS
Azathioprine is effective in maintaining remission. There is evidence for a steroid sparing effect.
Topics: Azathioprine; Crohn Disease; Humans; Immunosuppressive Agents; Mercaptopurine; Prodrugs
PubMed: 10796482
DOI: 10.1002/14651858.CD000067 -
Journal of Neuro-oncology Nov 2020These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma.
Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.
TARGET POPULATION
These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma.
IMAGING
Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma?
RECOMMENDATION
Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma.
SURGERY
Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma?
RECOMMENDATIONS
Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery.
NEUROPATHOLOGY
Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma.
RADIATION
Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques.
CHEMOTHERAPY
Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy.
MOLECULAR AND TARGETED THERAPY
Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies.
NOVEL THERAPIES
Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Evidence-Based Practice; Glioblastoma; Humans; Multimodal Imaging; Practice Guidelines as Topic
PubMed: 33215345
DOI: 10.1007/s11060-020-03607-4 -
The Cochrane Database of Systematic... Jul 2007Prevention of relapse is a major issue in the management of Crohn's disease. Corticosteroids and 5-ASA preparations are not effective for the maintenance of remission.... (Review)
Review
BACKGROUND
Prevention of relapse is a major issue in the management of Crohn's disease. Corticosteroids and 5-ASA preparations are not effective for the maintenance of remission. Methotrexate, infliximab, 6-mercaptopurine and its prodrug, azathioprine may be effective in maintaining remission, but these drugs may cause significant adverse events.
OBJECTIVES
To conduct a systematic review to evaluate the efficacy of enteral nutrition for the maintenance of remission in Crohn's disease.
SEARCH STRATEGY
MEDLINE (1966 to January 2007), EMBASE (1984 to January 2007) the Cochrane Central Register of Controlled Trials from the Cochrane Library (Issue 4, 2006) and the IBD/FBD Review Group Specialized Trials Register were searched. The articles cited in each publication were hand searched.
SELECTION CRITERIA
Randomised controlled trials which compared enteral nutrition with no intervention, placebo or with any other intervention were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Data extraction and assessment of methodological quality of included studies were independently performed by two authors. The main outcome measure was the occurrence of clinical or endoscopic relapse as defined by the primary studies. Odds ratios and 95% confidence intervals were calculated for dichotomous outcomes.
MAIN RESULTS
Two studies were identified that met the inclusion criteria and were included in the review. Statistical pooling of the results of these studies was not possible because the control interventions, and the way outcomes were assessed differed greatly between the two studies. In one study (Takagi 2006), patients who received half of their total daily calorie requirements as elemental diet and the remaining half by normal diet had a significantly lower relapse rate compared to patients who received unrestricted normal diet (9 of 26 versus 16 of 25; OR 0.3, 95% CI 0.09 to 0.94). In the other study (Verma 2001), elemental and polymeric feeds (providing between 35 and 50% of patients' pretrial calorie intake in addition to unrestricted normal food) were equally effective for maintenance of remission and allowing withdrawal of steroid therapy (8 of 19 versus 6 of 14; OR 0.97, 95% CI 0.24 to 3.92).
AUTHORS' CONCLUSIONS
The available evidence suggests that supplementary enteral nutritional may be effective for maintenance of remission in Crohn's disease. Whilst larger studies are needed to confirm these findings, enteral nutritional supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in Crohn's disease.
Topics: Crohn Disease; Enteral Nutrition; Humans; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 17636816
DOI: 10.1002/14651858.CD005984.pub2 -
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 -
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 -
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 -
Pharmacological Research 20085-Aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are 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 are 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; Chemistry, Pharmaceutical; Colitis, Ulcerative; Humans; Mesalamine; Patient Compliance
PubMed: 18801439
DOI: 10.1016/j.phrs.2008.08.003 -
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 -
The Cochrane Database of Systematic... May 2016This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear.
OBJECTIVES
To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children.
SEARCH METHODS
We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles.
SELECTION CRITERIA
Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence.
MAIN RESULTS
We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants.Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours.For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both.Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event.
AUTHORS' CONCLUSIONS
Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
Topics: Acetaminophen; Acute Pain; Adult; Analgesics; Child; Humans; Injections, Intravenous; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors
PubMed: 27213715
DOI: 10.1002/14651858.CD007126.pub3