***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The effect of Tegretol has been investigated in 71 patients with facial pain , using a single blind technique .  Tegretol was found to have an immediate good effect in 83 per cent of patients with typical trigeminal neuralgia , in 87 per cent of those with atypical neuralgia , and in 53 per cent of those with non‐neuralgiform facial pain .  Pain disappeared within the first 24 hours of treatment in 69 per cent and within the following 24 hours in a further 24 per cent . The 54 patients with a good immediate effect of Tegretol continued to take the drug after discharge , and 69 per cent of these were free of pain for over two years . Complications made withdrawal of treatment necessary in 5 per cent of the patients . One patient developed cardiac pain , three rash , three headache , nausea and vomiting , and two dizziness .  Tegretol acts by reducing the bulbar and spinal polysynaptic reflexes . It has a central action , in particular on the reticulo‐thalamic system . Our present knowledge of the mode of action of Tegretol supports the hypothesis that trigeminal neuralgia is due to pathological multineuronal reflexes in the trigeminal system on the level spinal trigeminal nuclei‐thalamus Abstract  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Carbazepine , Tegretol ( 5-carbamyl-dibenz (b , f)azepin ) , originally known as G.32883 and introduced in 1959 as an anticonvulsant , was first shown to have some effect in relieving the pain oftrigeminal neuralgia  by Blom ( 1962 , 1963 ) . Since then Spillane ( 1963 , 1964 ) , McArdle ( 1963 ) , and Taylor ( 1963 ) have confirmed that this drug has a specific effect in relieving the pain of trigeminal neuralgia in some 60 to 80 % of patients . This paper describes a controlled trial of  carbazepine  carried out simultaneously at The National Hospital , Queen Square , London , Cardiff Royal Infirmary , and Guy 's Hospital , London TIC DOULOUREUX is an often incapacitating affliction for which no completely satisfactory medical treatment has been available . While early observations that diphenylhydantoin has beneficial effects have been generally confirmed , 1 - 4 results with this drug are variable . Low doses are often ineffective , while the high dosages sometimes required for symptom control are poorly tolerated . Recently , Blom 5,6 and others 7 - 13 have reported that the paroxysmal pain of trigeminal neuralgia is promptly and consistently suppressed by the administration of carbamazepine ( Tegretol ) , an iminostilbene derivative with anticonvulsant activity . Chemically , the compound is 5 carbamyl-5H-dibenz ( b , f ) -azepine , and , as indicated by the structural formula ( Fig 1 ) , it is related to the antidepressant imipramine , but not to the hydantoins . While results with carbamazepine in typical tic douloureux are reported to be highly promising , the benefits observed in postherpetic and atypical facial neuralgias have been minimal . No controlled clinical trials with carbamazepine have been reported BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences & NA ; The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy ( DPN ) . The post hoc analysis is based on a 12 week , multinational , placebo‐controlled trial of pregabalin in which 401 patients were r and omized to treatment . Study measures included the Brief Pain Inventory short‐form ( BPI‐sf ) , EQ‐5D and other patient‐reported outcomes . Cutpoints were derived on the BPI‐sf 0–10 average pain numeric rating scale [ NRS ] to classify pain grade s of “ mild ” ( 1–3 ) , moderate ( 4–6 ) and severe ( 7–10 ) , adjusting for geographical regions where data were collected . Two different metrics were used to classify the importance of change in pain severity from baseline to 12 weeks : changes in pain severity grade s ( defined by cutpoint categories ) and percent reduction in the NRS ( categories ranging from 0–9 % to ≥50 % ) . An improvement in one pain grade or a ≥30 % reduction in the NRS served as determinants of a clinical ly important difference . Patients with a one‐ grade reduction in pain severity , either from “ severe‐to‐moderate ” or “ moderate‐to‐mild , ” had a 3‐point improvement the BPI‐sf Pain Interference Index ( PII ; a composite measure of function ) ; a reduction from “ severe‐to‐mild ” pain corresponded to a 6‐point improvement in the PII . Similarly , a reduction in the NRS of ≥30 % and ≥50 % corresponded to a 3‐point and a 5‐point improvement in the PII , respectively . Changes in pain were also associated with changes in health status . Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinical ly important changes in function and health status Summary A double blind crossover study with placebo and carbamazepine was done in 30 diabetic patients who presented diverse clinical types of peripheral diabetic neuropathy . The active drug offered symptomatic relief of all sensory manifestations in 28 cases . No effort was made to assess the action of carbamazepine upon motor or visceral manifestations of neuropathy . There were two complete failures . Untoward effects were frequent but usually mild and transient ; two patients presented a rash that required discontinuation of the drug . RésuméUne étude de cross over double aveugle avec placebo et carbamazépine a été effectuée chez 30 patients diabétiques présentant divers types cliniques de neuropathie diabétique périphérique . La drogue active apportait un soulagement symptomatique de toutes les manifestations sensorielles dans 28 cas . Aucun effort n'a été fait pour évaluer l'action de la carbamazépine sur les manifestations motrices ou viscérales de la neuropathie . Il y eut deux échecs complets . Les effets secondaires étaient fréquents , mais en général légers et temporaires . Deux patients présentèrent une éruption qui nécessita l'arrêt du traitement . ZusammenfassungAn 30 Diabetikern , die unterschiedliche Formen einer peripheren diabetischen Neuropathie aufwiesen , wurde eine Doppel-Blind-Austausch-Untersuchung mit Carbamazepin und einem Plazebo-Präparat durchgeführt . Bei 28 der Patienten führt die aktive Droge zu einer symptomatischen Besserung sämtlicher Symptome von Seiten des sensiblen Nevensystems . Die Wirkung von Carbamazepin auf die motorischen und visceralen Erscheinungsformen der Neuropathie wurde nicht geprüft . Es traten zwei komplette Therapie-Versager auf . Nebenwirkungen waren häufig festzustellen ; sie waren jedoch gewöhnlich leicht und klangen schnell ab . Bei zwei Patienten zwang das Auftreten eines Exanthems zum Absetzen des Präparates & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate  percentage  pain reduction  for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy Abstract Objective : To determine whether inappropriate subgroup analysis together with chance could change the conclusion of a systematic review of several r and omised trials of an ineffective treatment . Design : 44 r and omised controlled trials of DICE therapy for stroke were performed ( simulated by rolling different coloured dice ; two trials per investigator ) . Each roll of the dice yielded the outcome ( death or survival ) for that “ patient . ” Publication bias was also simulated . The results were combined in a systematic review . Setting : Edinburgh . Main outcome measure — Mortality . Results : The “ hypothesis generating ” trial suggested that DICE therapy provided complete protection against death from acute stroke . However , analysis of all the trials suggested a reduction of only 11 % ( SD 11 ) in the odds of death . A predefined subgroup analysis by colour of dice suggested that red dice therapy increased the odds by 9 % ( 22 ) . If the analysis excluded red dice trials and those of poor method ological quality the odds decreased by 22 % ( 13 , 2P=0.09 ) . Analysis of “ published ” trials showed a decrease of 23 % ( 13 , 2P=0.07 ) while analysis of only those in which the trialist had become familiar with the intervention showed a decrease of 39 % ( 17 , 2P=0.02 ) . Conclusion : The early benefits of DICE therapy were not confirmed by subsequent trials . A plausible ( but inappropriate ) subset analysis of the effects of treatment led to the qualitatively different conclusion that DICE therapy reduced mortality , whereas in truth it was ineffective . Chance influences the outcome of clinical trials and systematic review s of trials much more than many investigators realise , and 
    Output:
    
Most placebo controlled studies indicated that carbamazepine was better than placebo .
Serious adverse events were not reported consistently ; rashes were associated with carbamazepine .
Carbamazepine is effective in  chronic neuropathic pain  , with caveats .