***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: Background : Evidence -based pharmacological treatment options for patients with persistent inguinal postherniorrhaphy pain are lacking . Methods : Twenty-one male patients , with severe , unilateral , persistent inguinal postherniorrhaphy pain , participated in a r and omized , double-blind , placebo-controlled crossover trial , receiving lidocaine patch ( 5 % ) and placebo patch treatments in periods of 14 days separated by a 14-day wash-out period . Pain intensities ( at rest , during movement , and pressure evoked [ Numerical Rating Scale ] ) were assessed before treatment and on the last 3 days of each treatment period . Patients were a priori divided into two subgroups based on quantitative sensory testing ( + /− thermal “ hyposensitivity ” ) . Skin biopsies for intraepidermal nerve fiber density assessment were taken at baseline , and quantitative sensory testing was performed before and after each treatment period . The primary outcome was change in pain intensity assessed as the difference in summed pain intensity differences between lidocaine and placebo patch treatments . Results : There was no difference in summed pain intensity differences  between lidocaine and placebo patch treatments in all patients ( mean difference 6.2 % [ 95 % CI = −6.6 to 18.9 % ] ; P = 0.33 ) or in the two subgroups ( + /− thermal “ hyposensitivity ” ) . The quantitative sensory testing ( n = 21 ) demonstrated an increased pressure pain thresholds after lidocaine compared with placebo patch treatment . Baseline intraepidermal nerve fiber density ( n = 21 ) was lower on the pain side compared with the nonpain side ( −3.8 fibers per millimeter [ 95 % CI = −6.1 to −1.4 ] ; P = 0.003 ) . One patient developed mild erythema in the groin during both treatments . Conclusions : Lidocaine patch treatment did not reduce combined resting and dynamic pain ratings compared with placebo in patients with severe , persistent inguinal postherniorrhaphy pain Objective Oral amitriptyline , a tricyclic antidepressant , is effective for treating neuropathic pain . We conducted a double-blind , r and omized , placebo-controlled crossover study to evaluate the efficacy of topical 5 % amitriptyline and 5 % lidocaine in treating patients with neuropathic pain . Methods Thirty-five patients with postsurgical neuropathic pain , postherpetic neuralgia , or diabetic neuropathy with allodynia or hyperalgesia were assigned to receive 3 topical creams ( 5 % amitriptyline , 5 % lidocaine , or placebo ) in r and om sequence . The primary outcome measure was change in pain intensity ( baseline vs. posttreatment average pain ) using a 0 to 100 mm Visual Analog Scale . Secondary outcome measures included the McGill Pain Question naire , requirement for rescue medication , and patient satisfaction . Primary statistical comparisons were made with paired t tests or signed-rank tests . Results A reduction in pain intensity was observed with topical lidocaine ( P<0.05 ) . No significant change in pain intensity was found with topical amitriptyline or placebo . In pairwise comparison of treatments , topical lidocaine and placebo each reduced pain more than topical amitriptyline ( P<0.05 ) . Discussion This r and omized , placebo-controlled crossover study examining topical 5 % amitriptyline and 5 % lidocaine in the treatment of neuropathic pain showed that topical lidocaine reduced pain intensity but the clinical improvement is minimal and that topical 5 % amitriptyline was not effective 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 Objective Current therapies often have limited efficacy and untenable side effects when used to treat persistent incisional pain following cancer-related surgery .  Lidocaine patches reduce neuropathic pain from herpes zoster but their benefits for persistent cancer-related postsurgical incisional pain remain unclear . Study design Multicenter , double-blind , r and omized , two-period crossover trial . Material s and methods Twenty-eight cancer patients with postsurgical incisional pain were r and omly assigned to receive either lidocaine patches followed by placebo patches or the reverse . Each study period lasted 4 weeks . Patches were applied daily upon waking and left in place for a maximum of 18 h. The primary outcome measure , an 11-point pain intensity rating scale , was administered weekly . Secondary outcomes were administered weekly ( Brief Pain Inventory-Short Form(BPI-SF ) , Subject Global Impression of Change ) and at the end of each study period ( Short Form-Magill Pain Question naire , Linear Analogue Self Assessment Scale , Neuropathy Pain Scale , Pain Catastrophizing Scale , Profile of Mood States Short Form ) . Results Twenty-one patients completed the first period and 18 completed their crossover second phase . No significant intergroup differences were detected in pain intensity ratings . Few secondary end points were significantly different when subjects used the lidocaine versus placebo patches . BPI-SF interference scores were lower in patients using the lidocaine patch during the first study period , including several scores that achieved statistical significance , general activity ( p = 0.02 ) , work ( p = 0.04 ) , and relations with others ( p = 0.02 ) . Conclusion Lidocaine patch use did not significantly reduce pain intensity ratings or the majority of related secondary end points in cancer patients with persistent incisional pain & NA ; Post‐herpetic neuralgia ( PHN ) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly .  Topical local anesthetics have shown promise in both uncontrolled and controlled studies . Thirty‐five subjects with established PHN affecting the torso or extremities completed a four‐session , r and om order , double‐blind , vehicle‐controlled study of the analgesic effects of topically applied 5 % lidocaine in the form of a non‐woven polyethylene adhesive patch .  All subjects had allodynia on examination . Up to 3 patches , covering a maximum of 420 cm2 , were applied to cover the area of greatest pain as fully as possible . Lidocaine containing patches were applied in two of the four 12‐h‐long sessions , in one session vehicle patches were applied , and one session was a no‐treatment observation session . Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no‐treatment observation , and at all time points 4–12 h compared to vehicle patches . Lidocaine patches were superior to both no‐treatment observation and vehicle patches in averaged category pain relief scores . The highest blood Lidocaine level measured was 0.1 & mgr;g/ ml , indicating minimal systemic absorption of Lidocaine . Patch application was without systemic side effects and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5 % Lidocaine in patch form is easy to use and relieves post‐herpetic neuralgia 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 Postherpetic neuralgia ( PHN ) following herpes zoster is a common and disabling neuropathic pain syndrome . In a double‐blind , three‐session study , 5 % lidocaine gel or vehicle was applied simultaneously to both the area of pain and to the contralateral mirror‐image unaffected skin . In the local session , lidocaine gel was applied to the painful skin area . In the remote session , lidocaine gel was applied to mirror‐image skin . In the placebo session , vehicle was applied bilaterally . For cranial PHN , gel was applied without occlusion for 8 hours . For limb or torso PHN , gel was applied under occlusion for 24 hours . The 16 subjects with cranial PHN  reported pain relief significantly favoring local drug application at 30 minutes , 2 , 4 , and 8 hours . The 23 subjects with torso or limb PHN reported significantly lower pain intensity with local drug application at 8 hours and both pain relief and reduced pain intensity at 24 hours . Remote lidocaine application to mirror‐image skin was no different from placebo . No systemic adverse effects were reported and blood levels did not exceed 0.6 μg/ml . Topical application of 5 % lidocaine gel relieves PHN pain by a direct drug action on painful skin BACKGROUND Trigeminal nerve block has been widely used for trigeminal neuralgia . This may induce paraesthesia . The second division of the trigeminal nerve passes through the sphenopalatine ganglion , which is located posterior to the middle turbinate and is covered by a mucous membrane . We examined the effectiveness of intranasal lidocaine 8 % spray on paroxysmal pain in second-division trigeminal neuralgia . METHODS Twenty-five patients with second-division trigeminal neuralgia were r and omized to receive two sprays ( 0.2 ml ) of either lidocaine 8 % or saline placebo in the affected nostril using a metered-dose spray . After a 7 day period , patients were crossed over to receive the alternative treatment . The paroxysmal pain triggered by touching or moving face was assessed with a 10 cm visual analogue scale ( VAS ) before and 15 min after treatment . Patients used a descriptive scale to grade pain outcome , and were asked to note whether the pain returned and how long after therapy it recurred . RESULTS Intranasal lidocaine 8 % spray significantly decreased VAS [ baseline : 8.0 ( 2.0 ) cm , 15 min postspray : 1.5 ( 1.9 ) cm , mean ( SD ) ] , whereas the placebo spray did not [ 7.9 ( 2.0 ) cm , 7.6 ( 2.0 ) cm ] . Moreover , pain was described as moderate or better by 23 patients of the lidocaine spray and 1 of the placebo group . The effect of treatment persisted for 4.3 h ( range 0.5 - 24 h ) . CONCLUSIONS Intranasal lidocaine 8 % administered by a metered-dose spray produced prompt but temporary analgesia without serious adverse reactions in patients with second-division trigeminal neuralgia BACKGROUND : A topical lidocaine patch is effective in the treatment of posttraumatic peripheral neuropathy ( PTPN ) , but it is not suited for breakthrough pain because of difficulty with an additional application . Here , we examined the effect of 8 % lidocaine pump spray ( Xylocaine pump spray ® , XPS ) on peripher 
    Output:
    
In all but one study , third tier ( very low quality ) evidence indicated that lidocaine was better than placebo for some measure of pain relief .
Pooling multiple-dose studies across conditions demonstrated no clear evidence of an effect of lidocaine on the incidence of adverse events or withdrawals , but there were few events and the withdrawal phase of enriched enrolment design s is not suitable to assess the true impact of adverse events ( very low quality evidence ) .
This review found no evidence from good quality r and omised controlled studies to support the use of topical lidocaine to treat neuropathic pain , although individual studies indicated that it was effective for relief of pain .
Clinical experience also supports efficacy in some patients .