Biomedical subjects

R A Moore

Publications and source records attributed to R A Moore.

At least 19 recordsLinked to original sources

PubMed2002

Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical trial reports.

BACKGROUND: Evaluation of company clinical trial reports could provide information for meta-analysis at the commercial introduction of a new technology. METHODS: Clinical trial reports of sildenafil for erectile dysfunction from September 1997 were used for meta-analysis of randomised trials (at least four weeks duration) and using fixed or dose optimisation regimens. The main outcome sought was an erection, sufficiently rigid for penetration, followed by successful intercourse, and conducted at home. RESULTS: Ten randomised controlled trials fulfilled the inclusion criteria (2123 men given sildenafil and 1131 placebo). NNT or NNH were calculated for important efficacy, adverse event and discontinuation outcomes. Dose optimisation led to at least 60% of attempts at sexual intercourse being successful in 49% of men, compared with 11% with placebo; the NNT was 2.7 (95% confidence interval 2.3 to 3.3). For global improvement in erections the NNT was 1.7 (1.6 to 1.9). Treatment-related adverse events occurred in 30% of men on dose optimised sildenafil compared with 11% on placebo; the NNH was 5.4 (4.3 to 7.3). All cause discontinuations were less frequent with sildenafil (10%) than with placebo (20%). Sildenafil dose optimisation gave efficacy equivalent to the highest fixed doses, and adverse events equivalent to the lowest fixed doses. CONCLUSION: This review of clinical trial reports available at the time of licensing agreed with later reviews that had many more trials and patients. Making reports submitted for marketing approval available publicly would provide better information when it was most needed, and would improve evidence-based introduction of new technologies.

Erectile Dysfunction↗

PubMed2002

The hidden costs of arthritis treatment and the cost of new therapy--the burden of non-steroidal anti-inflammatory drug gastropathy.

Pain is very common throughout the world and is an increasing problem in the ageing population. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to treat pain and many are also available without prescription, or over the counter. These drugs are effective painkillers, but they can also have severe adverse effects, particularly on the upper gastrointestinal (GI) tract. Therapeutic decisions should be made using the best available evidence and there is a growing body of evidence showing that the new specific cyclooxygenase-2 (COX-2) inhibitors, or coxibs, are effective pain killers that do not cause GI harm. The risks associated with the use of NSAIDs are substantial, with a 1 in 1200 chance of dying from a major GI adverse effect after 2 months of NSAID therapy. These risks increase with age and are avoidable. The costs associated with the prevention and treatment of NSAID-induced GI adverse effects can more than double the cost of the original therapy and should be included when costing NSAID interventions. Taking these costs into account, the expense of switching from a conventional NSAID to a coxib is relatively modest. Compared with other interventions that society may be willing to consider to prevent one death, such as those for the rail (15 million Pounds) and road (100,000 Pounds) networks in the UK, the cost of preventing one death by switching to a coxib is much lower, with a high estimate being 20,000-30,000 Pounds, which is in line with the accepted benchmarks for the cost-effectiveness of medical interventions.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

S-carboxymethylcysteine in the treatment of glue ear: quantitative systematic review.

OBJECTIVE: To establish the clinical relevance of S-carboxymethylcysteine in the treatment of glue ear in children using measures approximating those saving a child from operation for grommet insertion. DATA SOURCES: Cochrane Library, MEDLINE, EMBASE, PubMed, reference lists and reviews were used for randomised controlled trials comparing S-carboxymethylcysteine with placebo. Seven trials involving 283 children and 146 ears were found. REVIEW METHODS: Studies were randomised, double-blind comparisons of S-carboxymethylcysteine (any dose and duration) with placebo in otitis media with effusion. Quality of trial reporting and validity of methods were assessed and used in sensitivity analysis. Main outcomes were relative benefit and number-needed-to-treat to prevent one grommet operation compared with placebo. RESULTS: Successful outcomes were obtained in 17% of children given placebo (range 5% to 38% in individual studies) and in 35% of children given S-carboxymethylcysteine (range 22 to 80%). For combined data (children and ears) the relative benefit was 2.0 (95%CI 1.4 to 2.8) and number-needed-to-treat 5.5 (95% confidence interval 3.8 to 9.8). Pooled data from trials of higher reporting quality (4/7) or methodological validity (3/7) tended to have lower efficacy but were not statistically different from those of lower quality or validity. CONCLUSION: S-carboxymethylcysteine is effective in the treatment of children with glue ear. For every five or six children treated with S-carboxymethylcysteine over one to three months, one will not undergo surgery for grommet insertion who would have done had they been given placebo. The confidence in this conclusion is limited because studies included relatively few children.

Anti-Infective Agents↗

PubMed2001

Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.

OBJECTIVE: To establish whether cannabis is an effective and safe treatment option in the management of pain. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. STUDY SELECTION: Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. DATA EXTRACTION: Independent data extraction; discrepancies resolved by consensus. DATA SYNTHESIS: 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. CONCLUSION: Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.

Analgesics, Non-Narcotic↗

PubMed2001

Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.

OBJECTIVE: To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy. DESIGN: Systematic review. DATA SOURCES: Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000. STUDIES: 30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours. RESULTS: Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: "high" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11. CONCLUSIONS: In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

Antiemetics↗

PubMed2001

Imiquimod for the treatment of genital warts: a quantitative systematic review.

OBJECTIVE: To review published randomised controlled trials to assess the benefit and harm of imiquimod in the treatment of external genital warts. DATA SOURCES: MEDLINE (1966 - December 2000), Cochrane Library (Issue 3, 2000) and PubMed (December 15, 2000), review articles and reference lists. REVIEW METHODS: Included studies had to be randomised trials of imiquimod, to be full published papers, and to have a comparison group. Quality of trial reporting was assessed. Relative benefit and number needed to treat were calculated for the main outcomes of wart clearance at the end of therapy, of at least 50% reduction in wart area, and of complete clearance at the end of treatment and no recurrence of warts during a follow-up period, as well as for adverse effect withdrawal or lack of efficacy withdrawal. RESULTS: There were six trials, all with quality scores of 3 (out of 5) or greater. In five trials with HIV-negative patients complete clearance of warts at the end of treatment occurred in 51% of patients treated with imiquimod 2% or 5% cream and 6% of placebo treated patients. The number needed to treat was 2.2 (95% confidence interval 2.0 to 2.6). In four trials at least 50% wart area reduction occurred with 72% of patients treated with imiquimod 5% cream and 20% of placebo treated patients. The number needed to treat was 1.9 (1.7 to 2.2). In three trials complete clearance of warts at the end of treatment plus no recurrence occurred in 37% of patients treated with imiquimod 5% cream and 4% of those treated with placebo. The number needed to treat was 3.0 (2.5 to 3.8). Adverse event withdrawal was rare and no more likely with imiquimod than with placebo. Imiquimod was not effective in one trial in HIV-positive patients. CONCLUSION: The evidence base for imiquimod in treating genital warts is of high quality and the necessary size from which to draw useful conclusions. Imiquimod is effective in home application, though not in patients with HIV infection with the evidence presently available.

AIDS-Related Opportunistic Infections↗

PubMed2001

Systematic review of the use of honey as a wound dressing.

OBJECTIVE: To investigate topical honey in superficial burns and wounds though a systematic review of randomised controlled trials. DATA SOURCES: Cochrane Library, MEDLINE, EMBASE, PubMed, reference lists and databases were used to seek randomised controlled trials. Seven randomised trials involved superficial burns, partial thickness burns, moderate to severe burns that included full thickness injury, and infected postoperative wounds. REVIEW METHODS: Studies were randomised trials using honey, published papers, with a comparator. Main outcomes were relative benefit and number-needed-to-treat to prevent an outcome relating to wound healing time or infection rate. RESULTS: One study in infected postoperative wounds compared honey with antiseptics plus systemic antibiotics. The number needed to treat with honey for good wound healing compared with antiseptic was 2.9 (95% confidence interval 1.7 to 9.7). Five studies in patients with partial thickness or superficial burns involved less than 40% of the body surface. Comparators were polyurethane film, amniotic membrane, potato peel and silver sulphadiazine. The number needed to treat for seven days with honey to produce one patient with a healed burn was 2.6 (2.1 to 3.4) compared with any other treatment and 2.7 (2.0 to 4.1) compared with potato and amniotic membrane. For some or all outcomes honey was superior to all these treatments. Time for healing was significantly shorter for honey than all these treatments. The quality of studies was low. CONCLUSION: Confidence in a conclusion that honey is a useful treatment for superficial wounds or burns is low. There is biological plausibility.

Anti-Bacterial Agents↗

PubMed2001

Detection of viral DNA and E4 protein in basal keratinocytes of experimental canine oral papillomavirus lesions.

We studied experimental canine oral papillomavirus (COPV) infection by in situ hybridization and immunohistochemistry of weekly biopsies. After 4 weeks, viral DNA in rete ridges suggested a keratinocyte stem cell target. Abundant viral DNA was seen in E4-positive cells only. E4 was predominantly cytoplasmic but also nuclear, being concentrated in the nucleoli during wart formation. Infected cells spread laterally along the basal layer and into the parabasal layers, accompanied by E7 transcription and increased mitoses. Most of the lower epithelium was positive for viral DNA, but, in mature warts, higher levels of E4 expression and genome amplification occurred in only sporadic superficial cells. L1 expression was late and in only a subset of E4-positive cells. During regression, viral DNA was less abundant in deep epithelial layers, suggesting downregulation of replication prior to replacement of infected cells from beneath. Detection of viral DNA in post-regression tissue indicated latent infection.

Animals↗

PubMed2001

Regression of canine oral papillomas is associated with infiltration of CD4+ and CD8+ lymphocytes.

Canine oral papillomavirus (COPV) infection is used in vaccine development against mucosal papillomaviruses. The predictable, spontaneous regression of the papillomas makes this an attractive system for analysis of cellular immunity. Immunohistochemical analysis of the timing and phenotype of immune cell infiltration revealed a marked influx of leukocytes during wart regression, including abundant CD4+ and CD8+ cells, with CD4+ cells being most numerous. Comparison of these findings, and those of immunohistochemistry using TCRalphabeta-, TCRgammadelta-, CD1a-, CD1c-, CD11a-, CD11b-, CD11c-, CD18-, CD21-, and CD49d-specific monoclonal antibodies, with previously published work in the human, ox, and rabbit models revealed important differences between these systems. Unlike bovine papillomavirus lesions, those of COPV do not have a significant gamma/delta T-cell infiltrate. Furthermore, COPV lesions had numerous CD4+ cells, unlike cottontail rabbit papillomavirus lesions. The lymphocyte infiltrate in the dog resembled that in human papillomavirus lesions, indicating that COPV is an appropriate model for human papillomavirus immunity.

Animals↗

PubMed2001

Intra-epithelial vaccination with COPV L1 DNA by particle-mediated DNA delivery protects against mucosal challenge with infectious COPV in beagle dogs.

Protection against viral challenge with canine oral papillomavirus (COPV) was achieved by immunisation via particle-mediated DNA delivery (PMDD) of a plasmid encoding the COPV L1 gene to cutaneous and oral mucosal sites in beagle dogs. The initial dose of approximately 9 microg of DNA was followed by two booster doses at 6 week intervals. A similar approach was used to vaccinate a control group of animals with plasmid DNA encoding the Hepatitis B virus S gene. Following challenge at the oral mucosa with COPV all animals vaccinated with the COPV L1 gene were protected against disease. However five of six animals in the control group developed COPV induced papillomas at the oral mucosa. Both cell-mediated lymphoproliferative and humoral antibody responses to the DNA vaccine were observed. Our data indicate that PMDD of plasmid DNA can protect against mucosal challenge with papillomavirus.

Animals↗

PubMed2001

Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.

BACKGROUND: Meta-analysis usually restricts the information pooled, for instance using only randomised, double-blind, placebo-controlled trials. This neglects other types of high quality information. This review explores using different information for the combination of paracetamol 1000 mg and codeine 60 mg in acute postoperative pain. RESULTS: Randomised, double-blind, placebo-controlled trials of paracetamol 1000 mg and codeine 60 mg had an NNT of 2.2 (95% confidence interval 1.7 to 2.9) for at least 50% pain relief over four to six hours in three trials with 197 patients. Computer simulation of randomised trials demonstrated 92% confidence that the simulated NNT was within +/- 0.5 of the underlying value of 2.2 with this number of patients. The result was supported a rational dose-response relationship for different doses of paracetamol and codeine in 17 additional trials with 1,195 patients. Three controlled trials lacking a placebo and with 117 patients treated with of paracetamol 1000 mg and codeine 60 mg had 73% (95%CI 56% to 81%) of patients with at least 50% pain relief, compared with 57% (48% to 66%) in placebo controlled trials. Six trials in acute pain were omitted because of design issues, like the use of different pain measures or multiple dosing regimens. In each paracetamol 1000 mg and codeine 60 mg was shown to be better than placebo or comparators for at least one measure. CONCLUSIONS: Different designs of high quality trials can be used to support limited information used in meta-analysis without recourse to low quality trials that might be biased.

Acetaminophen↗

PubMed2001

Rizatriptan for acute migraine.

BACKGROUND: There are a number of different drug treatments for acute migraine, including currently four triptans, with several more likely to become available in the future. There is a need for evidence-based information to help determine the balance of benefit and harm for acute migraine treatment. OBJECTIVES: To quantitatively assess the efficacy of a single dose of rizatriptan (Maxalt) for treating a single migraine attack using the outcomes of headache response and pain-free response at half-an-hour, one hour, two hours, and sustained relief over 24 hours. To express efficacy in terms of numbers-needed-to-treat (NNTs). SEARCH STRATEGY: Trials were identified by searching MEDLINE (1966-July 2000), EMBASE (1980-June 2000), the Cochrane Library (Issue 3, 2000) and the Oxford Pain Relief Database (1950-1994). Date of last search: July 2000. SELECTION CRITERIA: The inclusion criteria were randomised, placebo-controlled trials of rizatriptan for acute migraine; double-blind design; International Headache Society diagnostic criteria for migraine with or without aura; single migraine attack; single-dose treatment at standard doses; adult population; baseline pain of moderate or severe intensity using a four-point standardised rating scale; dichotomous or percentage data for at least one of the main efficacy outcomes; and full journal publication. DATA COLLECTION AND ANALYSIS: Main outcomes considered were i) headache response at two hours, ii) headache response at one hour, iii) pain-free response at two hours, iv) sustained relief over 24 hours, v) pain-free response at 24 hours and vi) adverse effects. Minor outcomes were headache response and pain-free response at half-an-hour and four hours, and pain-free response at one hour. Dichotomous or percentage data were extracted and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for each outcome. MAIN RESULTS: Seven trials met our inclusion criteria, with 2626 patients given rizatriptan and 902 given placebo. Significant benefit of rizatriptan over placebo was shown for both doses of rizatriptan (5 mg and 10 mg) for all five main efficacy outcomes (ranging from one to 24 hours). A dose response was seen for the main outcomes. It was not possible to analyse adverse effects information in a meaningful way. REVIEWER'S CONCLUSIONS: Rizatriptan 5 mg and 10 mg are effective in treating acute migraine, with a dose-related increase in efficacy.

Acute Disease↗

PubMed2001

Transcutaneous electrical nerve stimulation (TENS) for chronic pain.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is used in a variety of different clinical settings to treat a range of different acute and chronic pain conditions and has become popular with both patients and health professionals. OBJECTIVES: To evaluate the effectiveness of TENS in chronic pain. SEARCH STRATEGY: The Cochrane Library, Embase, Medline, CINAHL and The Oxford Pain Database were searched. Reference lists from retrieved reports and reviews were examined. Date of the most recent search: March 1999. SELECTION CRITERIA: RCTs were eligible if they included the following treatment comparisons: active TENS versus sham TENS controls active TENS versus no treatment controls active TENS versus active TENS controls (for instance High Frequency TENS vs Low Frequency TENS) Studies of patients suffering chronic pain for three months or more which included subjective outcome measures for pain intensity, or pain relief were eligible for evaluation in this review. No restrictions were made to language or sample size. Data from abstracts, letters, or unpublished studies, and studies of TENS in angina, headache and migraine, and dysmenorrhoea were not included. DATA COLLECTION AND ANALYSIS: Data were extracted and summarised on the following items: patients and details of pain condition, study treatments, study duration, design, methods, subjective pain outcome measures, methodological quality, results for pain outcome measures and adverse effects, and the conclusions made by the authors of the original studies. Extracted data and methodological quality of each report was confirmed by at least three of the reviewers. MAIN RESULTS: Of 107 reports identified from the searches, 88 were excluded as they did not fulfil the pre-defined entry criteria. Nineteen RCTs (from 18 reports) were evaluated. The included trials varied in terms of design, analgesic outcomes, chronic pain conditions, TENS treatments and overall methodological quality. Studies included single and multiple dose treatment comparisons of TENS. The studies were small. The reporting of the methods used and results for the analgesic outcomes were generally poor. TENS treatments and controls were often poorly defined. Few studies evaluated the long-term analgesic effectiveness of TENS and single dose evaluations of TENS are unhelpful in making clinical decisions of the long-term effectiveness of TENS in the management of chronic pain. Meta-analysis was not possible. Overall in 10 of 15 inactive control studies there was a positive analgesic outcome in favour of the active TENS treatments. For the multiple dose treatment comparison studies only three of seven were considered to be in favour of the active TENS treatments. For the active controlled studies, seven studies made direct comparisons between HFTENS and LFTENS. Five of seven studies could find no difference in terms of analgesic efficacy between HFTENS and LFTENS at any time point. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive; the published trials do not provide information on the stimulation parameters which are most likely to provide optimum pain relief, nor do they answer questions about long-term effectiveness. Large multi-centre randomised controlled trials of TENS in chronic pain are urgently needed.

Chronic Disease↗

PubMed2001

Eletriptan for acute migraine.

BACKGROUND: Eletriptan (Relpax) is a new triptan soon to be made available by prescription for the treatment of acute migraine. Currently five triptans are available by prescription and more are under development. In light of the many drugs for treating acute migraine, there is a need for evidence-based assessments to help determine the relative efficacy and harm of these treatments. OBJECTIVES: To determine the efficacy of eletriptan for treating a single migraine attack using the outcomes of headache response and pain-free response at 0.5, 1, 2 and 4 hours, and sustained relief over 24 hours. To express efficacy in terms of number-needed-to-treat (NNT). To determine the adverse effects of a single dose of eletriptan and express this in terms of number-needed-to-harm (NNH). To allow for the comparison of the efficacy of eletriptan with other migraine treatments evaluated systematically in the same way. SEARCH STRATEGY: Data from all Phase III randomised placebo-controlled trials were made available by the manufacturer, Pfizer Inc. To date, these trials comprise the only data on eletriptan relevant to this review in a published or unpublished form; thus, searches of electronic databases for further trials of eletriptan were not conducted. SELECTION CRITERIA: Trials of eletriptan for acute migraine; randomised allocation to treatment groups, including a placebo group; double-blind design; International Headache Society diagnostic criteria for migraine with or without aura; single migraine attack; single-dose treatment at standard doses; adult population; baseline pain of moderate or severe intensity using a 4-point standardised rating scale (0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain); and dichotomous or percentage data for at least one of the main efficacy outcomes. DATA COLLECTION AND ANALYSIS: Trials were scored for quality and data extracted by two independent reviewers. Dichotomous or percentage data were extracted and pooled to calculate the relative benefit (RB) or relative risk (RR) and NNTs or NNHs for a number of outcomes for eletriptan 20 mg, 40 mg and 80 mg. The main outcomes considered were headache response at 1 and 2 hours, pain-free response at 2 hours, sustained relief over 24 hours and adverse effects. Minor outcomes considered were headache response at 0.5 and 4 hours, and pain-free response at 0.5, 1 and 4 hours. MAIN RESULTS: Six trials met the inclusion criteria. Significant benefit of eletriptan over placebo was shown for eletriptan 20 mg, 40 mg and 80 mg for the primary efficacy outcomes of headache response and pain-free response at 2 hours. For headache response at 2 hours, the NNTs (with 95% confidence intervals) were 4.4 (3.4 to 6.2), 2.9 (2.6 to 3.3) and 2.6 (2.4 to 3.0) for eletriptan 20 mg, 40 mg and 80 mg, respectively. For pain-free response at 2 hours, the NNTs were 9.9 (6.9 to 18), 4.5 (4.0 to 5.1) and 3.7 (3.4 to 4.2), for eletriptan 20 mg, 40 and 80 mg, respectively. There was no significant difference in the incidence of major adverse effects between any dose of eletriptan and placebo. The incidence of minor adverse effects was significantly higher for all eletriptan doses than for placebo, with NNHs of 11 (95% confidence interval, 6.2 to 39), 7.0 (5.2 to 11) and 3.7 (3.1 to 4.5) for eletriptan 20 mg, 40 mg and 80 mg, respectively. REVIEWER'S CONCLUSIONS: Eletriptan 20 mg, 40 mg and 80 mg are effective for the treatment of an acute migraine attack. Effectiveness is dose-related, with statistically significant differences between doses for pain-free response and 24-hour outcomes. Eletriptan compares well with other triptans available for outcomes measured up to 2 hours and provides meaningful relief for 24 hours. Taken as a single dose, eletriptan was well tolerated and caused no major harm. The incidence of minor harm was dose-dependent, with 80 mg giving significantly more adverse effects than 40 mg.

Acute Disease↗

PubMed2001

Single-dose dipyrone for acute postoperative pain.

BACKGROUND: The use of dipyrone as an analgesic is controversial. It is used most commonly to treat postoperative pain, colic pain, cancer pain and migraine, and in many countries, eg, Russia, Spain, Brazil, and in many parts of South-America and Africa, it is the most popular non opioid first line analgesic. In others it has been banned (e.g. USA, UK) because of its association with potentially life-threatening blood dyscrasias such as agranulocytosis. Dipyrone is currently available in Austria, Belgium, France, Germany, Italy, The Netherlands, Spain, Switzerland, South Africa, Latin America, Russia, Israel and India. OBJECTIVES: To assess quantitatively the analgesic efficacy and adverse effects of single-dose dipyrone in randomised trials in moderate to severe postoperative pain. To compare the relative efficacy of dipyrone with other drugs assessed in the same way. SEARCH STRATEGY: Published reports were identified from Medline, Embase, the Cochrane Library (Issue 3 1999), LILACs and the Oxford Pain Relief Database. Additional studies were identified from bibliographies of retrieved reports. Date of the most recent search: December 1999. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, clinical trial, random allocation of patients to treatment groups, double-blind design, adult patients, pain of moderate to severe intensity at the baseline assessment, postoperative administration of study drugs, treatment arms which included dipyrone and placebo or active control and oral, rectal, intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information to yield the number of patients who obtained at least 50% pain relief. This was used to calculate the proportion of patients with, and number-needed-to-treat for, at least 50% pain relief over 4-6 hours. Single-dose adverse effect data were collected. MAIN RESULTS: Fifteen studies were included; eight used placebo and seven used an active control (oral dexketoprofen 12.5 mg or 25 mg, oral ketorolac 10 mg, intramuscular pethidine 100 mg or ketorolac 30 mg, intravenous tramadol 100 mg or rectal suprofen 300 mg). In five trials (288 patients) the mean response rate (proportion of patients with at least 50% pain relief) for single dose oral dipyrone 500 mg was 73% (range 54% to 87%) and with placebo it was 32% (19% to 41%) in moderate to severe postoperative pain over 4-6 hours. In two studies (113 patients) the response rate with oral dipyrone 1 g was 69% (61% and 77%) and with placebo it was 20% (11% and 25%). In one study (70 patients) the response rate with intramuscular dipyrone 2 g was 74% and with placebo it was 46%. No analyses could be conducted for adverse effects. The response rates in the active controlled trials were similar to those reported in the placebo controlled trials. REVIEWER'S CONCLUSIONS: Single-dose dipyrone appears to be of similar efficacy to ibuprofen 400 mg and other analgesics frequently used in the treatment of moderate to severe postoperative pain. The commonest adverse effects were somnolence, gastric discomfort and nausea.

Acute Disease↗

PubMed2001

Cecal volvulus causing postoperative intestinal obstruction: report of a case.

Cecal volvulus is a rare cause of intestinal obstruction after major abdominal surgery. A case of cecal volvulus occurring in the early postoperative period after left colon resection for malignancy is presented. Clinical evaluation and plain abdominal radiographs suggesting cecal volvulus prompted laparotomy and correction. Delay in diagnosis results in high mortality, and treatment depends largely on the viability of the involved intestine. This report describes the second case of cecal volvulus complicating a left colectomy. It was treated by detorsion and reperitonealization cecopexy.

Aged↗

PubMed2001

Seeking a simple measure of analgesia for mega-trials: is a single global assessment good enough?

We sought to investigate the potential of using a simple global estimation ('How effective do you think the treatment was?') as a measure of efficacy by comparing it with at least 50%maxTOTPAR (at least 50% of the maximum possible pain relief) in acute pain studies. One hundred and fifty randomized, double-blind trials included in 11 systematic reviews of single dose, oral analgesics for postoperative pain were used as a source of data. The relationship between the proportion of patients reporting the top two or three values on a five-point global scale and the proportion with at least 50%maxTOTPAR was investigated. Twenty-six trials provided data on the proportion reporting the top two categories (very good or excellent) and 27 gave data on the top three categories (good, very good or excellent). The relationship between the percentage of patients recording the top two categories on a five-point global scale and the proportion with at least 50%maxTOTPAR was fair (r(2)=0.67). That for the top three categories was less good (r(2)=0.57). Similar numbers-needed-to-treat were calculated for aspirin 600/650 mg and ibuprofen 400 mg using at least 50%maxTOTPAR and the top two categories. No real difference was seen in the correlation for standard wording compared to non-standard wording. Individual patient data were also used from four randomized, placebo-controlled, double-blind trials in postoperative pain. The frequency distribution for %maxTOTPAR was plotted for patients reporting each of the five categories on the global scale. A global assessment provides similar measures of analgesic efficacy as TOTPAR derived from hourly measurements, but the effects of adverse effects have yet to be understood.

Analgesia↗

PubMed2001

Diffuse lamellar keratitis: isolation of endotoxin and demonstration of the inflammatory potential in a rabbit laser in situ keratomileusis model.

PURPOSE: To systematically examine sources of endotoxin contamination in eye centers as a potential cause of diffuse lamellar keratitis (DLK) and to demonstrate the inflammatory potential of endotoxin in a rabbit model of laser in situ keratomileusis (LASIK) surgery. SETTING: University of Calgary, Calgary, Alberta, Canada. METHODS: In this prospective study, all water sources that routinely come in contact with LASIK instruments, including sterilizer reservoirs, eyedrops, microkeratome blades, and cleaning solutions, were examined for endotoxins at 5 eye centers. Bacterial cultures were performed on water samples from 5 sterilizer reservoirs. A LASIK flap was created in 8 rabbit eyes using an Automated Corneal Shaper microkeratome (Bausch & Lomb). The flaps were reflected, and a dose of endotoxin at various concentrations was placed on the interface. After 1 minute, the flap was irrigated and repositioned. The rabbit eyes were examined daily with a slitlamp biomicroscope for 3 days for the development of DLK, which was classified on a scale from grade 1 to 4 (mild to severe). The rabbits were killed at the conclusion of the study, and the interfaces were stained to rule out infectious etiologies. RESULTS: Endotoxin was detected in significant concentrations in tap water, filtered and distilled water, instrument washbasins, and sterilizer reservoirs at all 5 centers. The cultures of the water samples taken from the sterilizer reservoirs ranged from no growth to the presence of >100 colony-forming units of Flavobacterium and Pseudomonas aeruginosa. Endotoxins caused DLK-like interface inflammation in all eyes tested. Examination of stained scrapings showed no microorganisms in the interface of the rabbit eyes. CONCLUSION: Endotoxin contamination was detected in water sources that routinely come in contact with LASIK instruments. Endotoxins were capable of inducing interface inflammation in a rabbit model and may therefore be a significant factor in epidemic DLK.

Animals↗