human
***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: In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias & NA ; The double‐blinded r and omized controlled trial showed that daily repetitive transcranial magnetic stimulation of primary motor cortex provided short‐term positive effect on neuropathic pain without serious adverse events . & NA ; There is little evidence for multisession repetitive transcranial magnetic stimulation ( rTMS ) on pain relief in patients with neuropathic pain ( NP ) , although single‐session rTMS was suggested to provide transient pain relief in NP patients . We aim ed to assess the efficacy and safety of 10 daily rTMS in NP patients . We conducted a r and omized , double‐blind , sham‐controlled , crossover study at 7 centers . Seventy NP patients were r and omly assigned to 2 groups . A series of 10 daily 5‐Hz rTMS ( 500 pulses/session ) of primary motor cortex ( M1 ) or sham stimulation was applied to each patient with a follow‐up of 17 days . The primary outcome was short‐term pain relief assessed using a visual analogue scale ( VAS ) . The secondary outcomes were short‐term change in the short form of the McGill pain question naire ( SF‐MPQ ) , cumulative changes in the following scores ( VAS , SF‐MPQ , the Patient Global Impression of Change scale [ PGIC ] , and the Beck Depression Inventory [ BDI ] ) , and the incidence of adverse events . Analysis was by intention to treat . This trial is registered with the University hospital Medical Information Network Clinical Trials Registry . Sixty‐four NP patients were included in the intention‐to‐treat analysis . The real rTMS , compared with the sham , showed significant short‐term improvements in VAS and SF‐MPQ scores without a carry‐over effect . PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS . There were no significant cumulative improvements in VAS , SF‐MPQ , and BDI . No serious adverse events were observed . Our findings demonstrate that daily high‐frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results Objective . Pain is a patient-important outcome , but current reporting in r and omized controlled trials and systematic review s is often suboptimal , impeding clinical interpretation and decision making . Methods . A working group at the 2014 Outcome Measures in Rheumatology ( OMERACT 12 ) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic review s. Results For individual trials , authors should report , in addition to mean change , the proportion of patients achieving 1 or more thresholds of improvement from baseline pain ( e.g. , ≥ 20 % , ≥ 30 % , ≥ 50 % ) , achievement of a desirable pain state ( e.g. , no worse than mild pain ) , and /or a combination of change and state . Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation . When pooling data for meta analysis , authors should consider converting all continuous measures for pain to a 100 mm visual analog scale ( VAS ) for pain and use the established , minimally important difference ( MID ) of 10 mm , and the conventionally used , appreciably important differences of 20 mm , 30 mm , and 50 mm , to facilitate interpretation . Effects ≤ 0.5 units suggest a small or very small effect . To further increase interpretability , the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference . This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups . Conclusion . Presentation of relative effects regarding pain will facilitate interpretation of treatment effects Objective : Central poststroke pain ( CPSP ) is usually difficult to treat . Amitriptyline , the only oral preparation shown to be effective in a r and omized controlled trial , is often associated with a range of side effects related to the many mechanisms of actions of tricyclic antidepressants . We investigated the effect of lamotrigine , a drug that reduces neuronal hyperexcitability , on poststroke pain . Methods : Thirty consecutive patients with CPSP ( median age 59 years , range 37 to 77 ; median pain duration 2.0 years , range 0.3 to 12 ) from two centers participated in a r and omized , double-blind , placebo-controlled cross-over study . The study consisted of two 8-week treatment periods separated by 2 weeks of wash-out . The primary endpoint was the median value of the mean daily pain score during the last week of treatment while treated with 200 mg/d lamotrigine . Secondary endpoints were median pain scores while on lamotrigine 25 mg/d , 50 mg/d , and 100 mg/d ; a global pain score ; assessment of evoked pain ; areas of spontaneous pain ; and allodynia/dysesthesia . Results : Lamotrigine 200 mg/d reduced the median pain score to 5 , compared to 7 during placebo ( p = 0.01 ) in the intent-to-treat population of 27 patients . No significant effect was obtained at lower doses . Twelve patients ( 44 % ) responded to the treatment . There was a uniform tendency to reduction of all secondary outcome measures , but lamotrigine only had significant effects on some of the secondary outcome measures . Lamotrigine was well tolerated with few and transient side effects . Two mild rashes occurred during lamotrigine treatment , one causing withdrawal from study . Conclusions : Oral lamotrigine 200 mg daily is a well tolerated and moderately effective treatment for central poststroke pain . Lamotrigine may be an alternative to tricyclic antidepressants in the treatment of CPSP & NA ; A double‐blind , 3‐phase , cross‐over , placebo‐controlled trial of the pain‐relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post‐stroke pain ( CPSP ) but without signs of depression . Treatment was given , in r and omized order , for periods of 4 weeks , separated by 1 week wash‐out . The final doses were 75 and 800 mg/day , respectively , for amitriptyline and carbamazepine . The treatment effects were assessed by daily ratings of pain intensity on a 10‐step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5‐step verbal scale . For the assessment of depression the Comprehensive Psychopathological Rating Scale ( CPRS ) was used . Amitriptyline produced a statistically significant reduction of pain when compared to placebo . According to the global rating , 10 of the 15 patients were responders to this drug . The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration , since the median total ami‐ and nortriptyline concentrations were 497 and 247 nmol/1 , respectively , for responders and non‐responders . The early onset , together with the fact that the patients were not depressed , nor did they obtain reduced scores on ratings of depressive symptoms and signs , provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect . Five of the 14 patients treated with carbamazepine  reported some pain relief , but the effect did not reach statistical significance when compared to placebo . No correlation was found between effect and plasma concentration . In general , the patients tolerated the planned final dose of amitriptyline well . No final dose reduction was necessary . Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients . However , only 1 patient had to be taken off medication , on day 25 , due to drug interaction Objective : We describe the frequency , duration , clinical characteristics , and radiologic correlates of central poststroke pain  ( CPSP ) in young ischemic stroke survivors in a prospect i ve study setting . Methods : A question naire of pain and sensory abnormalities and EQ-5D quality -of-life question naire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry . Patients ( n = 58 ) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT , Brief Pain Inventory , and Beck Depression Inventory question naires . Results : Of the included 824 patients , 49 had CPSP ( 5.9 % ) , 246 patients ( 29.9 % ) had sensory abnormality without CPSP , and 529 patients ( 64.2 % ) had neither sensory abnormality nor CPSP . The median follow-up time from stroke was 8.5 years ( interquartile range 5.0–12.1 ) . Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP ( p = 0.007 ) as well as to those with no sensory abnormality and no CPSP ( p < 0.001 ) . Forty ( 82 % ) of the patients with CPSP had concomitant other pain . CPSP was associated with moderate ( p < 0.001 ) and severe ( p < 0.001 ) stroke symptoms , but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups . Stroke localization was not correlated with CPSP . Conclusions : Late persistent CPSP was found in 5.9 % of young stroke survivors and was associated with concomitant other pain , impaired quality of life , and moderate or severe stroke symptoms & NA ; Central post‐stroke pain ( CPSP ) is a neuropathic pain syndrome characterized by constant or intermittent pain in a body part occurring after stroke and associated with sensory abnormalities in the painful body part . This study describes CPSP prospect ively during the first year after stroke and characterizes the cerebrovascular lesions and neurological signs associated with the CPSP syndrome . Two hundred and sixty‐seven consecutively admitted patients younger than 81 years were examined in the first week , at 1 , 6 and 12 months after stroke . Sensibility to touch ( cotton wool ) , temperature ( 20 ° C and 40 ° C ) , and pinprick was studied using the contralateral face and extremity as control . A CT scan was done 8 ( median ) days ( range : 1–34 days ) after stroke . Two hundred and seven ( 78 % ) patients surviving at least 6 months who were able to communicate reliably formed the basis of the study . Abnormal sensory signs were found at least once in 87 ( 42 % ) patients . CPSP was found in 16 ( 8 % ) patients of whom all but 1 patient also had evoked dysesthesia or allodynia . Further 1 patient had persistent evoked dysesthesia but denied pain . CPSP was not related to sex or age . In patients with single acute cerebral lesions there were no relation between size or location of the lesions and the presence of CPSP . The pain was light in 6 ( 3 % ) patients and moderate to severe in 10 ( 5 % ) patients . The pain quality was usually lacerating or aching . Fifteen ( 94 % ) patients had decreased temperature , touch and pain sensibility and 9 ( 56 % ) reported allodynia to cold stimulation and another 9 ( 56 % ) patients reported this to touch . Pain onset was within 1 month after stroke in 10 ( 63 % ) patients , between 1 and 6 months in 3 ( 19 % ) patients and more than 6 months after stroke in 3 ( 1 
    Output:
    
agent
Results suggested that all therapies had little to no effect on pain and other patient-important outcomes .
Our findings are inconsistent with major clinical practice guidelines ; the available evidence suggests no beneficial effects of any therapies that research ers have evaluated in r and omized controlled trials
***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: In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias & NA ; The double‐blinded r and omized controlled trial showed that daily repetitive transcranial magnetic stimulation of primary motor cortex provided short‐term positive effect on neuropathic pain without serious adverse events . & NA ; There is little evidence for multisession repetitive transcranial magnetic stimulation ( rTMS ) on pain relief in patients with neuropathic pain ( NP ) , although single‐session rTMS was suggested to provide transient pain relief in NP patients . We aim ed to assess the efficacy and safety of 10 daily rTMS in NP patients . We conducted a r and omized , double‐blind , sham‐controlled , crossover study at 7 centers . Seventy NP patients were r and omly assigned to 2 groups . A series of 10 daily 5‐Hz rTMS ( 500 pulses/session ) of primary motor cortex ( M1 ) or sham stimulation was applied to each patient with a follow‐up of 17 days . The primary outcome was short‐term pain relief assessed using a visual analogue scale ( VAS ) . The secondary outcomes were short‐term change in the short form of the McGill pain question naire ( SF‐MPQ ) , cumulative changes in the following scores ( VAS , SF‐MPQ , the Patient Global Impression of Change scale [ PGIC ] , and the Beck Depression Inventory [ BDI ] ) , and the incidence of adverse events . Analysis was by intention to treat . This trial is registered with the University hospital Medical Information Network Clinical Trials Registry . Sixty‐four NP patients were included in the intention‐to‐treat analysis . The real rTMS , compared with the sham , showed significant short‐term improvements in VAS and SF‐MPQ scores without a carry‐over effect . PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS . There were no significant cumulative improvements in VAS , SF‐MPQ , and BDI . No serious adverse events were observed . Our findings demonstrate that daily high‐frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results Objective . Pain is a patient-important outcome , but current reporting in r and omized controlled trials and systematic review s is often suboptimal , impeding clinical interpretation and decision making . Methods . A working group at the 2014 Outcome Measures in Rheumatology ( OMERACT 12 ) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic review s. Results For individual trials , authors should report , in addition to mean change , the proportion of patients achieving 1 or more thresholds of improvement from baseline pain ( e.g. , ≥ 20 % , ≥ 30 % , ≥ 50 % ) , achievement of a desirable pain state ( e.g. , no worse than mild pain ) , and /or a combination of change and state . Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation . When pooling data for meta analysis , authors should consider converting all continuous measures for pain to a 100 mm visual analog scale ( VAS ) for pain and use the established , minimally important difference ( MID ) of 10 mm , and the conventionally used , appreciably important differences of 20 mm , 30 mm , and 50 mm , to facilitate interpretation . Effects ≤ 0.5 units suggest a small or very small effect . To further increase interpretability , the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference . This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups . Conclusion . Presentation of relative effects regarding pain will facilitate interpretation of treatment effects Objective : Central poststroke pain ( CPSP ) is usually difficult to treat . Amitriptyline , the only oral preparation shown to be effective in a r and omized controlled trial , is often associated with a range of side effects related to the many mechanisms of actions of tricyclic antidepressants . We investigated the effect of lamotrigine , a drug that reduces neuronal hyperexcitability , on poststroke pain . Methods : Thirty consecutive patients with CPSP ( median age 59 years , range 37 to 77 ; median pain duration 2.0 years , range 0.3 to 12 ) from two centers participated in a r and omized , double-blind , placebo-controlled cross-over study . The study consisted of two 8-week treatment periods separated by 2 weeks of wash-out . The primary endpoint was the median value of the mean daily pain score during the last week of treatment while treated with 200 mg/d lamotrigine . Secondary endpoints were median pain scores while on lamotrigine 25 mg/d , 50 mg/d , and 100 mg/d ; a global pain score ; assessment of evoked pain ; areas of spontaneous pain ; and allodynia/dysesthesia . Results : Lamotrigine 200 mg/d reduced the median pain score to 5 , compared to 7 during placebo ( p = 0.01 ) in the intent-to-treat population of 27 patients . No significant effect was obtained at lower doses . Twelve patients ( 44 % ) responded to the treatment . There was a uniform tendency to reduction of all secondary outcome measures , but lamotrigine only had significant effects on some of the secondary outcome measures . Lamotrigine was well tolerated with few and transient side effects . Two mild rashes occurred during lamotrigine treatment , one causing withdrawal from study . Conclusions : Oral lamotrigine 200 mg daily is a well tolerated and moderately effective treatment for central poststroke pain . Lamotrigine may be an alternative to tricyclic antidepressants in the treatment of CPSP & NA ; A double‐blind , 3‐phase , cross‐over , placebo‐controlled trial of the pain‐relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post‐stroke pain ( CPSP ) but without signs of depression . Treatment was given , in r and omized order , for periods of 4 weeks , separated by 1 week wash‐out . The final doses were 75 and 800 mg/day , respectively , for amitriptyline and carbamazepine . The treatment effects were assessed by daily ratings of pain intensity on a 10‐step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5‐step verbal scale . For the assessment of depression the Comprehensive Psychopathological Rating Scale ( CPRS ) was used . Amitriptyline produced a statistically significant reduction of pain when compared to placebo . According to the global rating , 10 of the 15 patients were responders to this drug . The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration , since the median total ami‐ and nortriptyline concentrations were 497 and 247 nmol/1 , respectively , for responders and non‐responders . The early onset , together with the fact that the patients were not depressed , nor did they obtain reduced scores on ratings of depressive symptoms and signs , provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect . Five of the 14 patients treated with carbamazepine  reported some pain relief , but the effect did not reach statistical significance when compared to placebo . No correlation was found between effect and plasma concentration . In general , the patients tolerated the planned final dose of amitriptyline well . No final dose reduction was necessary . Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients . However , only 1 patient had to be taken off medication , on day 25 , due to drug interaction Objective : We describe the frequency , duration , clinical characteristics , and radiologic correlates of central poststroke pain  ( CPSP ) in young ischemic stroke survivors in a prospect i ve study setting . Methods : A question naire of pain and sensory abnormalities and EQ-5D quality -of-life question naire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry . Patients ( n = 58 ) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT , Brief Pain Inventory , and Beck Depression Inventory question naires . Results : Of the included 824 patients , 49 had CPSP ( 5.9 % ) , 246 patients ( 29.9 % ) had sensory abnormality without CPSP , and 529 patients ( 64.2 % ) had neither sensory abnormality nor CPSP . The median follow-up time from stroke was 8.5 years ( interquartile range 5.0–12.1 ) . Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP ( p = 0.007 ) as well as to those with no sensory abnormality and no CPSP ( p < 0.001 ) . Forty ( 82 % ) of the patients with CPSP had concomitant other pain . CPSP was associated with moderate ( p < 0.001 ) and severe ( p < 0.001 ) stroke symptoms , but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups . Stroke localization was not correlated with CPSP . Conclusions : Late persistent CPSP was found in 5.9 % of young stroke survivors and was associated with concomitant other pain , impaired quality of life , and moderate or severe stroke symptoms & NA ; Central post‐stroke pain ( CPSP ) is a neuropathic pain syndrome characterized by constant or intermittent pain in a body part occurring after stroke and associated with sensory abnormalities in the painful body part . This study describes CPSP prospect ively during the first year after stroke and characterizes the cerebrovascular lesions and neurological signs associated with the CPSP syndrome . Two hundred and sixty‐seven consecutively admitted patients younger than 81 years were examined in the first week , at 1 , 6 and 12 months after stroke . Sensibility to touch ( cotton wool ) , temperature ( 20 ° C and 40 ° C ) , and pinprick was studied using the contralateral face and extremity as control . A CT scan was done 8 ( median ) days ( range : 1–34 days ) after stroke . Two hundred and seven ( 78 % ) patients surviving at least 6 months who were able to communicate reliably formed the basis of the study . Abnormal sensory signs were found at least once in 87 ( 42 % ) patients . CPSP was found in 16 ( 8 % ) patients of whom all but 1 patient also had evoked dysesthesia or allodynia . Further 1 patient had persistent evoked dysesthesia but denied pain . CPSP was not related to sex or age . In patients with single acute cerebral lesions there were no relation between size or location of the lesions and the presence of CPSP . The pain was light in 6 ( 3 % ) patients and moderate to severe in 10 ( 5 % ) patients . The pain quality was usually lacerating or aching . Fifteen ( 94 % ) patients had decreased temperature , touch and pain sensibility and 9 ( 56 % ) reported allodynia to cold stimulation and another 9 ( 56 % ) patients reported this to touch . Pain onset was within 1 month after stroke in 10 ( 63 % ) patients , between 1 and 6 months in 3 ( 19 % ) patients and more than 6 months after stroke in 3 ( 1 
    Output:
    