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The Cochrane Database of Systematic... Apr 2007Treatment of cancer is increasingly effective but associated with short and long term side effects. Oral side effects, including oral mucositis (mouth ulceration),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment of cancer is increasingly effective but associated with short and long term side effects. Oral side effects, including oral mucositis (mouth ulceration), remain a major source of illness despite the use of a variety of agents to treat them.
OBJECTIVES
To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy or radiotherapy or both.
SEARCH STRATEGY
Computerised searches of Cochrane Oral Health Group's Trials Register; Cochrane Pain, Palliative and Supportive Care Group's Trials Register; CENTRAL; MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. Date of the most recent searches June 2006: CENTRAL (The Cochrane Library 2006, Issue 2).
SELECTION CRITERIA
All randomised controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy or radiotherapy or both. Outcomes were oral mucositis, time to heal mucositis, oral pain, duration of pain control, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and quality of life.
DATA COLLECTION AND ANALYSIS
Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and withdrawals. Quality assessment was carried out on these three criteria. The Cochrane Oral Health Group statistical guidelines were followed and risk ratio (RR) values calculated using fixed effect models.
MAIN RESULTS
Twenty-six trials involving 1353 patients satisfied the inclusion criteria. Four agents, each in single trials, were found to be effective for improving (allopurinol RR 3.33, 95% confidence interval (CI) 1.06 to 10.49; granulocyte macrophage-colony stimulating factor RR 4.23, 95% CI 1.35 to 13.24; immunoglobulin RR 1.81, 95% CI 1.24 to 2.65; human placentral extract RR 4.50, 95% CI 2.29 to 8.86) or eradicating mucositis (allopurinol RR 19.00, 95% CI 1.17 to 307.63). Three of these trials were rated as at moderate risk of bias and one as at high risk of bias. The following agents were not found to be effective: benzydamine HCl, sucralfate, tetrachlorodecaoxide, chlorhexidine and 'magic' (lidocaine solution, diphenhydramine hydrochloride and aluminum hydroxide suspension). Six trials compared the time to heal and mucositis was found to heal more quickly with two interventions: granulocyte macrophage-colony stimulating factor when compared to povidone iodine, with mean difference -3.5 days (95% CI -4.1 to -2.9) and allopurinol compared to placebo, with mean difference -4.5 days (95% CI -5.8 to -3.2). Three trials compared patient controlled analgesia (PCA) to the continuous infusion method for controlling pain. There was no evidence of a difference, however, less opiate was used per hour for PCA, and the duration of pain was shorter. One trial demonstrated that pharmacokinetically based analgesia (PKPCA) reduced pain compared with PCA: however, more opiate was used with PKPCA.
AUTHORS' CONCLUSIONS
There is weak and unreliable evidence that allopurinol mouthwash, granulocyte macrophage-colony stimulating factor, immunoglobulin or human placental extract improve or eradicate mucositis. There is no evidence that patient controlled analgesia (PCA) is better than continuous infusion method for controlling pain, however, less opiate was used per hour, and duration of pain was shorter, for PCA. Further, well designed, placebo-controlled trials assessing the effectiveness of allopurinol mouthwash, granulocyte macrophage-colony stimulating factor, immunoglobulin, human placental extract, other interventions investigated in this review and new interventions for treating mucositis are needed.
Topics: Humans; Mouth Diseases; Mouth Mucosa; Neoplasms; Pain; Pain Management; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 17443514
DOI: 10.1002/14651858.CD001973.pub3 -
The Cochrane Database of Systematic... 2004Treatment of cancer is increasingly effective but associated with short and long-term side effects. Oral side effects, including oral mucositis (mouth ulceration),... (Review)
Review
BACKGROUND
Treatment of cancer is increasingly effective but associated with short and long-term side effects. Oral side effects, including oral mucositis (mouth ulceration), remain a major source of illness despite the use of a variety of agents to treat them.
OBJECTIVES
To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy and/or radiotherapy.
SEARCH STRATEGY
Computerised searches of Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. Date of the most recent searches August 2003: (CENTRAL) (The Cochrane Library Issue 3, 2003).
SELECTION CRITERIA
All randomised controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy and/or radiotherapy. Outcomes were oral mucositis, time to heal mucositis, oral pain, duration of pain control, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and quality of life.
DATA COLLECTION AND ANALYSIS
Data were independently extracted, in duplicate, by two reviewers. Authors were contacted for details of randomisation, blindness and withdrawals. Quality assessment was carried out on these three criteria. The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using fixed effect models.
MAIN RESULTS
Twenty-five trials involving 1292 patients satisfied the inclusion criteria. Three agents, each in single trials, were found to be effective for improving (allopurinol RR 3.33, 95% CI 1.06 to 10.49; immunoglobulin RR 1.81, 95% CI 1.24 to 2.65; human placentral extract RR 4.50, 95% CI 2.29 to 8.86) or eradicating mucositis (allopurinol RR 19.00, 95% CI 1.17 to 307.63). Two of these trials were rated as at moderate risk of bias and one as at high risk of bias. The following agents were not found to be effective: benzydamine HCl, sucralfate, tetrachlorodecaoxide, chlorhexidine and 'magic' (lidocaine solution, diphenhydramine hydrochloride and aluminum hydroxide suspension). Six trials compared the time to heal and mucositis was found to heal more quickly with two interventions: Granulocyte Macrophage-Colony Stimulating Factor when compared to povidone iodine, with mean difference -3.5 days (95% CI -4.1 to -2.9) and allopurinol compared to placebo, with mean difference -4.5 days (95% CI -5.8 to -3.2). Three trials compared patient controlled analgesia (PCA) to the continuous infusion method for controlling pain. There was no evidence of a difference, however, less opiate was used per hour for PCA, and the duration of pain was shorter. One trial demonstrated that pharmacokinetically based analgesia (PKPCA) reduced pain compared with PCA, however more opiate was used with PKPCA.
REVIEWERS' CONCLUSIONS
There is weak and unreliable evidence that allopurinol mouthwash, vitamin E, immunoglobulin or human placental extract improve or eradicate mucositis. There is no evidence that patient controlled analgesia (PCA) is better than continuous infusion method for controlling pain, however, less opiate was used per hour, and duration of pain was shorter, for PCA. Further, well designed, placebo-controlled trials assessing the effectiveness of allopurinol mouthwash, immunoglobulin, human placental extract, other interventions investigated in this review and new interventions for treating mucositis are needed.
Topics: Humans; Mouth Diseases; Mouth Mucosa; Neoplasms; Pain; Pain Management; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 15106165
DOI: 10.1002/14651858.CD001973.pub2 -
The Lancet. Infectious Diseases Feb 2004We have reviewed evidence of adverse events after exposure to aluminium-containing vaccines against diphtheria, tetanus, and pertussis (DTP), alone or in combination,... (Comparative Study)
Comparative Study Meta-Analysis Review
We have reviewed evidence of adverse events after exposure to aluminium-containing vaccines against diphtheria, tetanus, and pertussis (DTP), alone or in combination, compared with identical vaccines, either without aluminium or containing aluminium in different concentrations. The study is a systematic review with meta-analysis. We searched the Cochrane Vaccines Field Register, the Cochrane Library, Medline, Embase, Biological Abstracts, Science Citation Index, and the Vaccine Adverse Event Reporting System website for relevant studies. Reference lists of retrieved articles were scanned for further studies. We included randomised and semi-randomised trials and comparative cohort studies if the report gave sufficient information for us to extract aluminium concentration, vaccine composition, and safety outcomes. Two reviewers extracted data in a standard way from all included studies and assessed the methodological quality of the studies. We identified 35 reports of studies and included three randomised trials, four semi-randomised trials, and one cohort study. We did a meta-analysis of data from five studies around two main comparisons (vaccines containing aluminium hydroxide vs no adjuvant in children aged up to 18 months and vaccines containing different types of aluminium vs no adjuvants in children aged 10-16 years). In young children, vaccines with aluminium hydroxide caused significantly more erythema and induration than plain vaccines (odds ratio 1.87 [95% CI 1.57-2.24]) and significantly fewer reactions of all types (0.21 [0.15-0.28]). The frequencies of local reactions of all types, collapse or convulsions, and persistent crying or screaming did not differ between the two cohorts of the trials. In older children, there was no association between exposure to aluminium-containing vaccines and onset of (local) induration, swelling, or a raised temperature, but there was an association with local pain lasting up to 14 days (2.05 [1.25-3.38]). We found no evidence that aluminium salts in vaccines cause any serious or long-lasting adverse events. Despite a lack of good-quality evidence we do not recommend that any further research on this topic is undertaken.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Aluminum; Aluminum Hydroxide; Child; Clinical Trials as Topic; Cohort Studies; Diphtheria-Tetanus-Pertussis Vaccine; Erythema; Humans; Immunization; Infant; Pain; Randomized Controlled Trials as Topic; Time Factors
PubMed: 14871632
DOI: 10.1016/S1473-3099(04)00927-2 -
Alimentary Pharmacology & Therapeutics Nov 2003Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic... (Review)
Review
BACKGROUND
Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking.
AIM
As experimental data suggest a role of bile acids in the regulation of hepatic drug metabolism at both the transcriptional and post-transcriptional level, the literature was screened for adverse drug reactions and drug interactions related to ursodeoxycholic acid.
METHODS
A systematic review of the literature was performed using a refined search strategy to evaluate the adverse effects of ursodeoxycholic acid and its interactions with other drugs.
RESULTS
Ursodeoxycholic acid caused diarrhoea in a small proportion of patients. Rare skin reactions were due to drug adjuvants rather than the active substance. Decompensation of liver cirrhosis was reported after the administration of ursodeoxycholic acid in single cases of end-stage primary biliary cirrhosis. Recurrent right upper quadrant abdominal pain was incidentally observed. The absorption of ursodeoxycholic acid was impaired by colestyramine, colestimide, colestipol, aluminium hydroxide and smectite. Metabolic drug interactions were reported for the cytochrome P4503A substrates, ciclosporin, nitrendipine and dapsone.
CONCLUSIONS
Ursodeoxycholic acid is generally well tolerated. Drug absorption interactions with anion exchange resins deserve consideration. Metabolic interactions with compounds metabolized by cytochrome P4503A are to be expected.
Topics: Cholagogues and Choleretics; Chronic Disease; Drug Interactions; Female; Humans; Liver Diseases; Pregnancy; Pregnancy Complications; Ursodeoxycholic Acid
PubMed: 14616161
DOI: 10.1046/j.1365-2036.2003.01792.x -
The Cochrane Database of Systematic... 2002Treatment of cancer is increasingly effective but associated with short and long-term side effects. Oral side effects, including oral mucositis (ulceration), remain a... (Review)
Review
BACKGROUND
Treatment of cancer is increasingly effective but associated with short and long-term side effects. Oral side effects, including oral mucositis (ulceration), remain a major source of illness despite the use of a variety of agents to treat them.
OBJECTIVES
To assess the effectiveness of interventions for treating oral mucositis or its associated pain in patients with cancer receiving chemotherapy and/or radiotherapy.
SEARCH STRATEGY
Computerised searches of Cochrane Oral Health Group Specialised Register, CCTR, MEDLINE and EMBASE were undertaken. Reference lists from relevant articles were searched. Authors of eligible trials were contacted to identify trials and obtain additional information. Date of most recent searches: May 2001 (CCTR 2001, issue 3)
SELECTION CRITERIA
All randomised controlled trials comparing agents prescribed to treat oral mucositis in people receiving chemotherapy and/or radiotherapy. Outcomes were oral mucositis, oral pain, dysphagia, systemic infection, amount of analgesia, length of hospitalisation, cost and quality of life.
DATA COLLECTION AND ANALYSIS
Data were independently extracted, in duplicate, by two reviewers. Authors were contacted for details of randomisation, blindness and withdrawals. Quality assessment was carried out on these three criteria. Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using fixed effects models as no significant heterogeneity was detected (P>0.1).
MAIN RESULTS
Fifteen trials involving 876 patients satisfied the inclusion criteria. Two agents, each in single trials, were found to be effective for improving (allopurinol RR=0.63 95%CI 0.42 to 0.96) or eradicating mucositis (allopurinol RR=0.59 95%CI 0.42 to 0.84; vitamin E RR=0.38 95%CI 0.14 to 0.97). The following agents were not found to be effective: benzydamine HCl, sucralfate, tetrachlorodecaoxide, chlorhexidine and "magic" (lidocaine solution, diphenhydramine hydrochloride and aluminum hydroxide suspension). Three trials compared patient controlled analgesia (PCA) to the continuous infusion method for controlling pain. There was no evidence of a difference, however, less opiate was used per hour for PCA. One trial demonstrated that pharmacokinetically based analgesia (PKPCA) reduced pain compared with PCA, however more opiate was used with PKCA.
REVIEWER'S CONCLUSIONS
There is weak and unreliable evidence that allopurinol mouthwash and vitamin E improves or eradicates mucositis. There is no evidence that patient controlled analgesia (PCA) is better than continuous infusion method for controlling pain, however, less opiate was used per hour for PCA. Further, well designed, placebo-controlled trials assessing the effectiveness of allopurinol mouthwash, vitamin E and new interventions for treating mucositis are needed.
Topics: Humans; Mouth Diseases; Mouth Mucosa; Neoplasms; Pain; Pain Management; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 11869616
DOI: 10.1002/14651858.CD001973 -
The Cochrane Database of Systematic... 2000Gastro-oesophageal reflux (GOR) is an extremely common and usually self limiting condition in infants. When treatment is required, Cisapride, a pro-kinetic agent, has... (Review)
Review
BACKGROUND
Gastro-oesophageal reflux (GOR) is an extremely common and usually self limiting condition in infants. When treatment is required, Cisapride, a pro-kinetic agent, has been commonly prescribed for the symptomatic management of GOR. There have been recent reports of possibly serious adverse events e.g. an increased QTc interval, cardiac arrhythmias, and death, associated with the use of Cisapride.
OBJECTIVES
To determine the effectiveness of Cisapride for symptoms of GOR in children compared with placebo or any other non-surgical treatments.
SEARCH STRATEGY
Searches were conducted of the Cochrane Central Trials Register and the specialised Trials register of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group, MEDLINE and Embase. Reference lists of relevant review articles and identified trials were scrutinised and forward citation searches were performed in the Science Citation Index on all trials identified.
SELECTION CRITERIA
Randomised controlled trials that compared oral Cisapride therapy with placebo or with other non-surgical treatments for children with a diagnosis of GOR were included. Only studies in which Cisapride was administered orally for a minimum of one week and which documented at least one of the primary outcomes were included.
DATA COLLECTION AND ANALYSIS
The primary outcomes were defined as a change in symptoms at the end of treatment, presence of adverse events, occurrence of clinical complications, and weight gain. The secondary outcomes included physiological measures of GOR or histological evidence of oesophagitis. We dichotomised symptoms into 'same or worse' vs 'improved' and calculated summary odds ratios. Continuous measures of GOR (e.g. reflux index) were summarised as a weighted mean difference. All outcomes were analysed using a random effects method. Sensitivity analyses were also performed.
MAIN RESULTS
Searches identified eight trials which met the inclusion criteria. Seven trials (a total of 236 participants) compared Cisapride with placebo. The odds ratio for 'same or worse' vs 'improved symptoms' at the end of treatment was 0.34 (95%CI 0.10, 1.19), thus showing no statistically significant difference between the two interventions. There was significant heterogeneity between the studies and the funnel plot suggested substantial publication bias. In the sensitivity analysis, the definition of outcomes was changed to 'any symptoms' vs 'no symptoms'. This resulted in the exclusion of three trials (one of them the largest, best quality trial). The resulting pooled odds ratio showed a significant effect of Cisapride (OR 0.19, 95%CI 0.08, 0.44). There were fewer adverse events with placebo than with Cisapride, but the difference was not statistically significant (OR 1.80, 95%CI 0.87, 3.70) and the result was based on small numbers. Cisapride compared with placebo produced a statistically significant reduction in the reflux index (weighted mean difference -6.49, 95%CI -10.13, -2.85), but as reflux index and clinical symptoms are poorly correlated, the clinical importance of this finding is uncertain. Other measures of oesophageal pH monitoring did not reach significance. One included study compared Cisapride with Gaviscon (or Gaviscon and Carobel). The odds ratio for 'same or worse' vs 'improvement' in the Cisapride group compared with Gaviscon was 3.26 (95%CI 0.93, 11.38).
REVIEWER'S CONCLUSIONS
We found no clear evidence that Cisapride reduces symptoms of GOR. The results suggested substantial publication bias favouring studies showing a positive effect of Cisapride. Due to reports of serious adverse events, the company will stop marketing the drug as of July 14th, 2000 and therefore a larger study to provide more conclusive evidence of the effect of Cisapride is no longer possible.
Topics: Alginates; Aluminum Hydroxide; Anti-Ulcer Agents; Cisapride; Drug Combinations; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Infant; Infant, Newborn; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Silicic Acid; Sodium Bicarbonate
PubMed: 10908549
DOI: 10.1002/14651858.CD002300