A multi-center international study on the spinal cord independence measure, version IV: Rasch psychometric validation.

CONTEXT: The Spinal Cord Independence Measure is a comprehensive functional rating scale for individuals with spinal cord lesion (SCL). OBJECTIVE: To validate the scores of the three subscales of SCIM IV, the fourth version of SCIM, using advanced statistical methods. STUDY DESIGN: Multi-center cohort study. SETTING: Nineteen SCL units in 11 countries. METHODS: SCIM developers created SCIM IV following comments by experts, included more accurate definitions of scoring criteria in the SCIM IV form, and adjusted it to assess specific conditions or situations that the third version, SCIM III, does not address. Professional staff members assessed 648 SCL inpatients, using SCIM IV and SCIM III, at admission to rehabilitation, and at discharge. The authors examined the validity and reliability of SCIM IV subscale scores using Rasch analysis. RESULTS: The study included inpatients aged 16-87 years old. SCIM IV subscale scores fit the Rasch model. All item infit and most item outfit mean-square indices were below 1.4; statistically distinct strata of abilities were 2.6-6; most categories were properly ordered; item hierarchy was stable across most clinical subgroups and countries. In a few items, however, we found misfit or category threshold disordering. We found SCIM III and SCIM IV Rasch properties to be comparable. CONCLUSIONS: Rasch analysis suggests that the scores of each SCIM IV subscale are reliable and valid. This reinforces the justification for using SCIM IV in clinical practice and research.

WITHDRAWN: Gabapentin for acute and chronic pain.

BACKGROUND: February 2009: The authors are aware of unpublished trial data for Gabapentin which could affect the results of this review. This information together with that from trials published since 2005, will be considered when this review is updated in 2009.Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of gabapentin for pain management in clinical practice. SEARCH STRATEGY: Randomised trials of gabapentin in acute, chronic or cancer pain were identified by MEDLINE (1966 to Nov 2004), EMBASE (1994 to Nov 2004), SIGLE (1980 to Jan 2004) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004). Additional studies were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: January 2004. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of gabapentin in participants with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent review authors, and trials were quality scored. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal. MAIN RESULTS: Fourteen reports describing 15 studies of gabapentin were considered eligible (1468 participants). One was a study of acute pain. The remainder included the following conditions: post-herpetic neuralgia (two studies), diabetic neuropathy (seven studies), a cancer related neuropathic pain (one study) phantom limb pain (one study), Guillain Barré syndrome (one study), spinal chord injury pain (one study) and various neuropathic pains (one study).The study in acute post-operative pain (70 participants) showed no benefit for gabapentin compared to placebo for pain at rest.In chronic pain, the NNT for improvement in all trials with evaluable data is 4.3 (95% CI 3.5 to 5.7). Forty two percent of participants improved on gabapentin compared to 19% on placebo. The number needed to harm (NNH) for adverse events leading to withdrawal from a trial was not significant. Fourteen percent of participants withdrew from active arms compared to 10% in placebo arms. The NNH for minor harm was 3.7 (95% CI 2.4 to 5.4). The NNT for effective pain relief in diabetic neuropathy was 2.9 (95% CI 2.2 to 4.3) and for post herpetic neuralgia 3.9 (95% CI 3 to 5.7). AUTHORS' CONCLUSIONS: There is evidence to show that gabapentin is effective in neuropathic pain. There is limited evidence to show that gabapentin is ineffective in acute pain.

Single dose dipyrone for acute postoperative pain.

BACKGROUND: Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. OBJECTIVES: To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. SEARCH STRATEGY: The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. SELECTION CRITERIA: Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248 participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No serious adverse events were reported. AUTHORS' CONCLUSIONS: Based on very limited information, single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and fewer would need rescue medication, over 4 to 6 hours.

Opioids in chronic non-cancer pain: systematic review of efficacy and safety.

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.

Efficacy and safety of valdecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials.

Our objective was to determine the efficacy and safety of valdecoxib (a cyclo-oxygenase 2 inhibitor) in the treatment of arthritis. Randomised, controlled trials comparing 10 or 20mg valdecoxib with placebo or non-steroidal anti-inflammatory drugs (NSAIDs) in patients with active osteoarthritis or rheumatoid arthritis. The manufacturer provided clinical trial reports. Data were combined through meta-analysis. Main outcomes were patient global rating of arthritis, arthritis pain, Western Ontario and McMaster Universities indices for osteoarthritis, American College of Rheumatology indices for rheumatoid arthritis, discontinuation, endoscopic ulcers, clinically significant upper gastrointestinal or renal events. Nine trials (five in osteoarthritis, four in rheumatoid arthritis) were included with 5726 patients. Overall, valdecoxib 10 and 20mg were superior to placebo and equivalent in efficacy to maximum daily doses of NSAIDs. Significantly fewer discontinuations because of gastrointestinal adverse events (4% versus 8%), or endoscopic ulcers of 3mm or more (5% versus 13%) occurred with valdecoxib compared with NSAIDs. Clinically significant upper gastrointestinal events occurred in 2/2733 (0.1%) with valdecoxib compared with 8/1846 (0.4%) with NSAIDs. Rates of clinically significant renal events were the same (2-3%) for valdecoxib and NSAIDs. At an appropriate dose valdecoxib was as effective as NSAIDs in osteoarthritis and rheumatoid arthritis. There were fewer gastrointestinal adverse event withdrawals and endoscopically detected ulcers. Convincing evidence of reduced major gastrointestinal adverse events could not be addressed by the trials.

Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis.

UNLABELLED: : A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases, and writing to manufacturers. We identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses. RESULTS: Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice.

Rofecoxib for dysmenorrhoea: meta-analysis using individual patient data.

BACKGROUND: Individual patient meta-analysis to determine the analgesic efficacy and adverse effects of single-dose rofecoxib in primary dysmenorrhoea. METHODS: Individual patient information was available from three randomised, double blind, placebo and active controlled trials of rofecoxib. Data were combined through meta-analysis. Number-needed-to-treat (NNT) for at least 50% pain relief and the proportion of patients who had taken rescue medication over 12 hours were calculated. Information was collected on adverse effects. RESULTS: For single-dose rofecoxib 50 mg compared with placebo, the NNTs (with 95% CI) for at least 50% pain relief were 3.2 (2.4 to 4.5) at six, 3.1 (2.4 to 9.0) at eight, and 3.7 (2.8 to 5.6) at 12 hours. For naproxen sodium 550 mg they were 3.1 (2.4 to 4.4) at six, 3.0 (2.3 to 4.2) at eight, and 3.8 (2.7 to 6.1) at 12 hours. The proportion of patients who needed rescue medication within 12 hours was 27% with rofecoxib 50 mg, 29% with naproxen sodium 550 mg, and 50% with placebo. In the single-dose trial, the proportion of patients reporting any adverse effect was 8% (4/49) with rofecoxib 50 mg, 12% (6/49) with ibuprofen 400 mg, and 6% (3/49) with placebo. In the other two multiple dose trials, the proportion of patients reporting any adverse effect was 23% (42/179) with rofecoxib 50 mg, 24% (45/181) with naproxen sodium 550 mg, and 18% (33/178) with placebo. CONCLUSIONS: Single dose rofecoxib 50 mg provided similar pain relief to naproxen sodium 550 mg over 12 hours. The duration of analgesia with rofecoxib 50 mg was similar to that of naproxen sodium 550 mg. Adverse effects were uncommon suggesting safety in short-term use of rofecoxib and naproxen sodium. Future research should include restriction on daily life and absence from work or school as outcomes.

Outcomes in acute pain trials: systematic review of what was reported?

Single-dose clinical trial methods for evaluating analgesics have been used successfully for over 50 years. The aims of this review were to examine which pain measurement scales have been used in high quality acute pain trials, to investigate other common measurements or characteristics, to confirm that different scales used by standard methods give the same estimate of analgesic effect, to investigate remedication methodologies and the potential of 'time to remedication' as a standard outcome. Published reports of randomised, double blind, placebo-controlled trials, investigating at least 20 adult patients (10 patients per treatment arm) experiencing moderate or severe pain using at least one standard pain intensity or pain relief scale were sought. Key design features, outputs and outcomes were catalogued for each report. The main outcomes reported were misleading, detailing only the mean values of data with a demonstrably skewed distribution. After 50 years, the reporting of results from acute pain trials warrants a fresh look. Possible improvements include reporting the number of patients with certain levels of pain relief, or the actual number (percentage) of patients with a certain level of pain relief at a certain time, or more useful information on remedication from trials of at least 12 h duration. Most useful would be all three. Further exploration would only be possible from analysis at the individual patient level.

Topical NSAIDs for acute pain: a meta-analysis.

BACKGROUND: A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design. RESULTS: Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating acute painful conditions for one week.

Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain.

OBJECTIVE: To determine the efficacy and safety of topical rubefacients containing salicylates in acute and chronic pain. DATA SOURCES: Electronic databases and manufacturers of salicylates. STUDY SELECTION: Randomised double blind trials comparing topical rubefacients with placebo or another active treatment, in adults with acute or chronic pain, and reporting dichotomous information, around a 50% reduction in pain, and analyses at one week for acute conditions and two weeks for chronic conditions. DATA EXTRACTION: Relative benefit and number needed to treat, analysis of adverse events, and withdrawals. DATA SYNTHESIS: Three double blind placebo controlled trials had information on 182 patients with acute conditions. Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8). Six double blind placebo controlled trials had information on 429 patients with chronic conditions. Topical salicylate was significantly better than placebo (relative benefit 1.5, 1.3 to 1.9; number needed to treat 5.3, 3.6 to 10.2), but larger, more valid studies were without significant effect. Local adverse events and withdrawals were generally rare in trials that reported them. CONCLUSIONS: Based on limited information, topically applied rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for rubefacients are unreliable owing to a lack of good clinical trials.

Systematic review of topical capsaicin for the treatment of chronic pain.

OBJECTIVE: To determine the efficacy and safety of topically applied capsaicin for chronic pain from neuropathic or musculoskeletal disorders. DATA SOURCES: Cochrane Library, Medline, Embase, PubMed, an in-house database, and contact with manufacturers of topical capsaicin. STUDY SELECTION: Randomised controlled trials comparing topically applied capsaicin with placebo or another treatment in adults with chronic pain. DATA EXTRACTION: Primary outcome was dichotomous information for the number of patients with about a 50% reduction in pain. Outcomes were extracted at four weeks for musculoskeletal conditions and eight weeks for neuropathic conditions. Secondary outcomes were adverse events and withdrawals due to adverse events. DATA SYNTHESIS: Six double blind placebo controlled trials (656 patients) were pooled for analysis of neuropathic conditions. The relative benefit from topical capsaicin 0.075% compared with placebo was 1.4 (95% confidence interval 1.2 to 1.7) and the number needed to treat was 5.7 (4.0 to 10.0). Three double blind placebo controlled trials (368 patients) were pooled for analysis of musculoskeletal conditions. The relative benefit from topical capsaicin 0.025% or plaster compared with placebo was 1.5 (1.1 to 2.0) and the number needed to treat was 8.1 (4.6 to 34). Around one third of patients experienced local adverse events with capsaicin, which would not have been the case with placebo. CONCLUSIONS: Although topically applied capsaicin has moderate to poor efficacy in the treatment of chronic musculoskeletal or neuropathic pain, it may be useful as an adjunct or sole therapy for a small number of patients who are unresponsive to, or intolerant of, other treatments.

Individual patient meta-analysis of single-dose rofecoxib in postoperative pain.

BACKGROUND: Individual patient meta-analysis to determine the analgesic efficacy and adverse effects of single-dose rofecoxib in acute postoperative pain. METHODS: Individual patient information was available from 14 trials; 13 in dental and one in postsurgical pain. For each patient the percentage of maximum possible pain relief (%maxTOTPAR) was determined at different time points. The proportion of patients with at least 50% maxTOTPAR, and number-needed-to-treat (NNT) for at least 50% maxTOTPAR, were then calculated, with time when 50% of patients had remedicated (TTR50) and number-needed-to-harm (NNH) for adverse effects. RESULTS: In dental pain, for rofecoxib 50 mg (1330 patients) compared with placebo (570 patients) the NNT was 1.9 (95% confidence interval 1.8 to 2.1) for six hours, 2.0 (1.8 to 2.1) at eight, 2.4 (2.2 to 2.6) at 12, and 2.8 (2.5 to 3.1) at 24 hours. The TTR50 was 15.5 hours. Adverse effects were uncommon, though post-extraction alveolitis (dry socket) occurred more often with rofecoxib 50 mg than with placebo, NNH 24 (14 to 80). For postsurgical pain in one trial (163 patients), the NNT for rofecoxib 50 mg for six hours was 3.9 (2.6 to 7.8), the TTR50 was 5.8 hours, and multiple-dose adverse effects over five days occurred at similar rates with rofecoxib 50 mg and placebo. CONCLUSIONS: Single-dose rofecoxib 50 mg is an effective treatment with long-lasting analgesia and few adverse effects in dental pain. More information is required to confirm efficacy in postsurgical pain.

Pain and analgesic response after third molar extraction and other postsurgical pain.

There is uncertainty over whether the patient group in which acute pain studies are conducted (pain model) has any influence on the estimate of analgesic efficacy. Data from four recently updated systematic reviews of aspirin 600/650 mg, paracetamol 600/650 mg, paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model. Area under the pain relief versus time curve equivalent to at least 50% maximum pain relief over 6 h was used as the outcome measure. Event rates with treatment and placebo, and relative benefit (RB) and number needed to treat (NNT) were used as outputs from the meta-analyses. The event rate with placebo was systematically statistically lower for dental than postsurgical pain for all four treatments. Event rates with analgesics, RB and NNT were infrequently different between the pain models. Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven, and, on balance, no major difference is likely.

Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review.

BACKGROUND: Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions, including the treatment of postoperative pain. This review aims to assess the efficacy, safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults, compared with placebo. METHODS: The Cochrane Library (issue 4 2002), EMBASE, PubMed, MEDLINE and an in-house database were searched for randomised, double blind, placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over 4 to 6 hours. Relative benefit and number-needed-to-treat were then calculated. The percentage of patients with any adverse event, number-needed-to-harm, and time to remedication were also calculated. RESULTS: Ten trials with 996 patients in met the inclusion criteria. Six trials compared naproxen sodium 550 mg (252 patients) with placebo (248 patients); the NNT for at least 50% pain relief over six hours was 2.6 (95% confidence interval 2.2 to 3.2). There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo. Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg (206 patients) and 2.6 hours for placebo (205 patients). Four other trials used lower doses. CONCLUSION: A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain. A low incidence of adverse events was found, although these were not reported consistently.

Oral valdecoxib and injected parecoxib for acute postoperative pain: a quantitative systematic review.

BACKGROUND: Clinical trials suggest that cyclo-oxygenase-2 specific inhibitors (coxibs) are an effective treatment for acute postoperative pain. The aims of this systematic review were to examine the evidence for oral valdecoxib and injected parecoxib, and quantify efficacy and adverse effects. METHODS: Information from randomized, double-blind studies in acute postoperative pain was sought. The area under the pain relief versus time curve over four to six hours was dichotomized using validated equations to derive the proportion of patients with treatment and placebo with at least 50% pain relief over four to six hours and calculate the number-needed-to-treat (NNT). Information on duration of analgesia and adverse events was also collected. RESULTS: The NNT for one patient to experience at least 50% relief over six hours following a single oral dose of valdecoxib 20 mg and 40 mg was 1.7 (1.4 to 2.0) and 1.6 (1.4 to 1.8) respectively. The NNT for one patient to have at least 50% relief over four to six hours with parecoxib 20 mg IV and 40 mg IV was 3.0 (2.3 to 4.1) and 2.3 (2.0 to 2.6) respectively. Mean time to remedication (weighted by trial size) was >24 hours with valdecoxib 40 mg, 8.7 hours with parecoxib 40 mg IV and 1.7 to 1.8 hours with placebo. There were no statistical differences between treatment and placebo for any adverse effect. CONCLUSION: Both oral valdecoxib and injected parecoxib are effective treatments for acute postoperative pain.

Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomised, double blind trials.

BACKGROUND: Statins alter lipid concentrations. This systematic review determined the efficacy of particular statins, in terms of their ability to alter cholesterol. REVIEW METHODS: PubMed, the Cochrane Library, references lists of reports, and reviews were searched (September 2001) for randomised, double blind trials of statins for cholesterol in trials of 12 weeks or longer. Mean change in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides was calculated using pooled data for particular statins, and for particular doses of a statin. Pre-planned sensitivity analyses were used to determine the effects of initial concentration of total cholesterol, study duration, the effects of major trials, and effects in placebo versus active controlled trials. Information was not collected on adverse events. RESULTS: Different statins at a range of doses reduced total cholesterol by 17-35% and LDL-cholesterol by 24-49% from baseline. Lower doses of statins generally produced less cholesterol lowering, though for most statins in trials of 12 weeks or longer there was at best only a weak relationship between dose and cholesterol reduction. Duration of treatment and baseline total cholesterol concentration did not alter the amount of the benefit attained. CONCLUSIONS: Statins are effective medicines and confer benefit to patients in terms of primary and secondary prevention of coronary heart disease. Reductions in total cholesterol of 25% or more and LDL cholesterol of more than 30% were recorded for fixed doses of simvastatin 40 mg, atorvastatin 10 mg, and rosuvastatin 5 mg and 10 mg.

Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials.

BACKGROUND: Benign prostatic hyperplasia affects older men. This systematic review determined efficacy and adverse effects of finasteride. REVIEW METHODS: PubMed, the Cochrane Library, reference lists of reports, and reviews were searched for randomised, double-blind trials of finasteride in benign prostatic hyperplasia. Outcomes included symptom score, urinary flow rate, prostate volume, discontinuation, and adverse effects. Relative risk and NNT or NNH were calculated for dichotomous data. Sensitivity analyses assessed influences of baseline symptom severity, initial prostate volume, a dominating trial, and previous interventions. RESULTS: Three trials had active controls and 19 had placebo. In placebo-controlled trials, 8820 patients received finasteride 5 mg and 5909 placebo over 3-48 months. Over 48 months finasteride produced greater improvements in total symptom score, maximum urinary flow rate, and prostate volume. Significantly more sexual dysfunction, impotence, ejaculation disorder and decreased libido occurred with finasteride at 12 months; the NNH for any sexual dysfunction at 12 months was 14. Significantly fewer men treated with finasteride experienced acute retention or had surgery at 24 or 48 months than with placebo; at 12 months the NNT was 49 (31 to 112) to avoid one acute urinary retention and 31 (21 to 61) to avoid one surgery. Sensitivity analyses showed benefit with finasteride 5 mg to be constant irrespective of the initial prostate volume. CONCLUSIONS: Information from many patients in studies of high quality showed beneficial effects of finasteride in terms of symptoms, flow rate and prostate volume. More utility would result if patient centred outcomes were reported in dichotomous form.

Ibuprofen 400 mg is effective in women, and women are well represented in trials.

BACKGROUND: A recent article in the New Scientist argued that women were under-represented in clinical trials which, until now, had masked the finding that ibuprofen 400 mg was ineffective in women. METHODS: Meta-analysis of randomised, double-blind placebo-controlled trials of ibuprofen 400 mg in acute pain, and use of individual patient information were planned to test the hypothesis that ibuprofen is ineffective in women. For each trial the proportion of women participating, the number of patients with at least 50% pain relief and the overall event rate for ibuprofen 400 mg and placebo was calculated. For each patient percentage pain relief was calculated, and the numbers of women and men achieving at least 50% pain relief used to calculate number-needed-to-treat (NNT) for ibuprofen 400 mg compared to placebo. RESULTS: Thirty-seven included trials had 3,577 patients, 67% of whom were women. The proportion with at least 50% pain relief was unaffected by how many women were included. In an analysis of 678 individual patients the proportion of women and men with at least 50% pain relief was the same, NNT 3.4 (2.6 to 4.6) and 2.5 (2.0 to 3.3) respectively. CONCLUSION: There is no clinically meaningful difference in the efficacy of ibuprofen 400 mg between men and women experiencing moderate to severe postoperative pain and women were well represented.