***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 The limitations of current treatments for postherpetic neuralgia ( PHN ) have led to the investigation of localised , non-systemic alternatives . NGX-4010 , a high-concentration ( 8 % ) capsaicin dermal patch , was developed to treat patients with neuropathic pain . We report the results of a r and omised , double blind , 12-week study of the efficacy and safety of one application of NGX-4010 in patients with PHN . METHODS In this multicentre , double-blind , parallel-group trial , 402 patients were r and omly assigned to one 60-min application of NGX-4010 ( 640 microg/cm(2 ) [ 8 % capsaicin ] ) or a low-concentration capsaicin control patch ( 3.2 microg/cm(2 ) [ 0.04 % capsaicin ] ) . Patients were aged 18 - 90 years , had had postherpetic neuralgia for at least 6 months , and had an average baseline numeric pain rating scale ( NPRS ) score of 3 to 9 . The primary efficacy endpoint was percentage change in NPRS score from baseline to weeks two to eight . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00115310 . FINDINGS Patients who were r and omly assigned to NGX-4010 ( n=206 ) had a significantly greater reduction in pain during weeks two to eight than did patients who had the control patch ( n=196 ) . The mean changes in NPRS score were -29.6%vs -19.9 % ( difference -9.7 % , 95 % CI -15.47 to -3.95 ; p=0.001 ) . 87 ( 42 % ) patients who received NGX-4010 and 63 ( 32 % ) controls had a 30 % or greater reduction in mean NPRS score ( odds ratio [ OR ] 1.56 , 95 % CI 1.03 to 2.37 ; p=0.03 ) . The patients who had NGX-4010 had significant improvements in pain during weeks two to 12 ( mean change in NPRS score -29.9%vs -20.4 % , difference -9.5 , -15.39 to -3.61 ; p=0.002 ) . Transient blood pressure changes associated with changes in pain level were recorded on the day of treatment , and short-lasting erythema and pain at the site of application were common , self-limited , and generally mild to moderate in the NGX-4010 group and less frequent and severe in the controls . INTERPRETATION One 60-min application of NGX-4010 provided rapid and sustained pain relief in patients with postherpetic neuralgia . No adverse events were associated with treatment except for local reactions at the site of application and those related to treatment-associated pain 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 Uncontrolled studies have indicated that topically applied capsaicin may be a safe and effective treatment for postherpetic neuralgia .  In a double-blind study 32 elderly patients with chronic postherpetic neuralgia were treated with either capsaicin cream or its vehicle for a 6-week period . Response to treatment was evaluated by visual analogue scales of pain and of pain relief , together with changes in a categoric pain scale and in a physician 's global evaluation . Significantly greater relief in the capsaicin-treated group compared with vehicle was observed for all efficacy variables . After 6 weeks almost 80 % of capsaicin-treated patients experienced some relief from their pain . Because capsaicin avoids problems with drug interactions and systemic toxicity , we suggest that topical capsaicin be considered for initial management of postherpetic neuralgia Eighteen patients with the post-mastectomy pain syndrome ( PMPS )  form the basis of this study . PMPS probably occurs in a minority of women after mastectomy . The onset of persistent pain usually occurred immediately or very shortly after the operation . The pain location or sensory findings implied involvement of the territories of other cutaneous branches of the intercostal nerves as well as the intercostobrachial nerve . A variety of treatment approaches were unsatisfactory . Twelve of 14 patients completing treatment with topical 0.025 % capsaicin showed improvement after 4 weeks and 8 ( 57 % ) were judged to be good or excellent responses . Six months after the trial 's completion 50 % of those followed continued to have good pain relief . This therapy should now be subjected to a r and omized , double-blind , placebo-controlled trial An 8-week , double-blind , vehicle-controlled study was conducted to determine the effectiveness of topical capsaicin 0.075 % cream in relieving  pain associated with diabetic neuropathy . Patients were selected who experienced moderate to very severe pain , which interfered with sleep or activities on a daily basis , and who were unresponsive or intolerant to conventional therapy . The results after 8 weeks showed a statistically significant difference in favor of the capsaicin-treated patients , with 90 % of these patients improved . The results of this study indicate that topical capsaicin 0.075 % cream is safe and effective in managing painful diabetic neuropathy CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials .  DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials PURPOSE A minority of cancer survivors develops long-term postsurgical neuropathic pain . Based on evidence that capsaicin , the pungent ingredient in hot chili peppers , might be useful for treating neuropathic pain , we developed the present clinical trial . PATIENTS AND METHODS Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study . After stratification , patients were to receive 8 weeks of a 0.075 % capsaicin cream followed by 8 weeks of an identical-appearing placebo cream , or vice versa . A capsaicin/placebo cream was to be applied to the painful site four times daily . Treatment evaluation was performed by patient-completed weekly question naires . RESULTS During the first 8-week study period , the capsaicin-cream arm was associated with substantially more skin burning , skin redness , and coughing ( P < .0001 for each ) . Nonetheless , treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin . The capsaicin cream arm had substantially more pain relief ( P = .01 ) after the first 8 weeks , with an average pain reduction of 53 % versus 17 % . On completion of the 16-week study period , patients were asked which treatment period was most beneficial . Of the responding patients , 60 % chose the capsaicin arm , 18 % chose the placebo arm , and 22 % chose neither ( P = .001 ) . CONCLUSION A topical capsaicin cream decreases postsurgical neuropathic pain and , despite some toxicities , is preferred by patients over a placebo by a three-to-one margin among those expressing a preference Distal symmetrical peripheral neuropathy ( DSPN ) is a particularly distressing pain syndrome associated with human immunodeficiency virus ( HIV ) disease . Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes , and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN . This multicenter , controlled , r and omized , double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity , pain relief , sensory perception , quality of life , mood , and function for patients who received topical capsaicin  to the corresponding measures for patients who received the vehicle only . Twenty-six subjects were enrolled in the study . At the end of 1 week , subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle ( Mann-Whitney test ; P = 0.042 ) . The dropout rate was higher for the capsaicin group ( 67 % ) than for the vehicle group ( 18 % ) ( chi 2 test of association ; P = 0.014 ) . There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain , worst pain , pain relief , sensory perception , quality of life , mood , or function at study entry or at any time during the 4-week trial . These results suggest capsaicin is ineffect 
    Output:
    
Capsaicin , either as repeated application of a low dose ( 0.075 % ) cream , or a single application of a high dose ( 8 % ) patch may provide a degree of pain relief to some patients with painful neuropathic conditions .
Local skin irritation , which is often mild and transient but may lead to withdrawal , is common .
Systemic adverse effects are rare .