R Andrew Moore

BACKGROUND: Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. OBJECTIVES: To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. SELECTION CRITERIA: Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. MAIN RESULTS: There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above. AUTHORS' CONCLUSIONS: Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.

Abstract Objective: To quantify the impact of duplicate data on estimates of efficacy. Design: Systematic search for published full reports of randomised controlled trials investigating ondansetron's effect on postoperative emesis. Abstracts were not considered. Data sources: Eighty four trials (11 980 patients receiving ondansetron) published between 1991 and September 1996. Main outcome measures: Percentage of duplicated trials and patient data. Estimation of antiemetic efficacy (prevention of emesis) of the most duplicated ondansetron regimen. Comparison between the efficacy of non-duplicated and duplicated data. Results: Data from nine trials had been published in 14 further reports, duplicating data from 3335 patients receiving ondansetron; none used a clear cross reference. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports not subject to duplicate publication, three reports subject to duplicate publication, and six duplicates of those three reports. The number needed to treat to prevent vomiting within 24 hours was 9.5 (95% confidence interval 6.9 to 15) in the 16 non-duplicated reports and 3.9 (3.3 to 4.8) in the three reports which were duplicated (P<0.00001). When these 19 were combined the number needed to treat was 6.4 (5.3 to 7.9). When all original and duplicate reports were combined (n=25) the apparent number needed to treat improved to 4.9 (4.4 to 5.6). Conclusions: By searching systematically we found 17% of published full reports of randomised trials and 28% of the patient data were duplicated. Trials reporting greater treatment effect were significantly more likely to be duplicated. Inclusion of duplicated data in meta-analysis led to a 23% overestimation of ondansetron's antiemetic efficacy. Key messages Although publishing the same data more than once is strongly discouraged, there is no evidence of the impact of duplicate data on meta-analysis Re-analysing an important trial, and cross referencing to original reports (overt duplication), may be necessary and valuable in some circumstances Covert duplication, masked by change of authors, of language, or by adding extra data, causes problems. One danger is that patient data are analysed more than once in meta-analysis 17% of systematically searched randomised trials of ondansetron as a postoperative antiemetic were covert duplicates and resulted in 28% of patient data being duplicated. None of these reports cross references the original source. Duplication lead to an overestimation of ondansetron's antiemetic efficacy of 23%. Trials reporting greater treatment effect were significantly more likely to be duplicated Covert duplication of data has major implications for the assessment of drug efficacy and safety

Introduction METHODS Finding all the relevant trials Judging the quality of trials Pain measurement: study design and validity Estimating relative effectiveness Combining data and interpreting the results Existing systematic reviews ACUTE PAIN Introduction Oral Ibuprofen and diclofenac in postoperative pain Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain Topically applied non-steroidal anti-inflammatory drugs Injected morphine in postoperative pain Dihydrocodeine in postoperative pain Dextropropoxyphene in postoperative pain Single patient data meta-analysis of 3,453 postoperative patients: oral tramadol versus placebo, codeine, and combination analgesics Pain relief from intra-articular morphine after knee surgery Analgesic efficacy of peripheral opioids Pre-emptive analgesia: a systematic review of clinical studies to 1994 Trancutaneous Electrical Nerve Stimulation in Acute Postoperative Pain TENS in labour pains Acute pain - conclusion CHRONIC PAIN Introduction Radiotherapy for painful bone metastases Transcutaneous Electrical Pain stimulation in chronic pain Intravenous regional sympathetic blockade for reflex sympathetic dystrophy Epidural corticosteroids for sciatica Spinal cord stimulators for back pain Steroid injections for shoulder disorders Anticonvulsant drugs Antidepressants in neuropathic pain Systemic local anaesthetic type drugs in chronic pain Topical capsaicin Chronic pain conclusion

BACKGROUND: Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality. METHODS: Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted. RESULTS: Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3-50%) overall, and 12% (3-25%) in studies based in the community (27, n = 69,975), 47% (31-50%) in nursing homes (3, n = 1481), and 40% (40-72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic. CONCLUSION: Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.

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.