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: BACKGROUND Autologous bone graft is the so-called gold st and ard for reconstruction of bone defects and nonunions . The most frequent complication is donor site pain . The iliac crest is a common source for autologous bone graft . The purpose of this study was to determine whether a continuous infusion of 0.5 % bupivacaine into the iliac crest harvest site provides pain relief that is superior to the relief provided by systemic narcotic pain medication alone in patients undergoing reconstructive orthopaedic trauma procedures . METHODS A prospect i ve , double-blind r and omized study of patients over eighteen years of age who were undergoing harvesting of iliac crest bone graft was conducted . The patients were r and omized to the treatment arm ( bupivacaine infusion pump ) or the placebo arm . Postoperatively , all study patients received morphine sulfate with use of a patient-controlled analgesia pump . The patients recorded the pain at the donor and recipient sites with use of a scale ranging from 0 to 10 . The use of systemic narcotic medication was recorded . Independent- sample s t tests were used to assess differences in perceived pain relief between the treatment and control groups at zero , eight , sixteen , twenty-four , thirty-two , forty , and forty-eight hours after surgery . Pain was also assessed at two and six weeks postoperatively . RESULTS Sixty patients were enrolled . Across all data points , except pain at the recipient site at twenty-four hours , no significant differences in the perception of pain were found between the bupivacaine group and the placebo group . On the average , patients in the treatment group reported more pain than those in the control group . No significant difference was found between the two groups with regard to the amount of narcotic medication used . CONCLUSIONS No difference in perceived pain was found between the groups . The results of this small , unstratified study indicate that continuous infusion of bupivacaine at iliac crest bone-graft sites during the postoperative period is not an effective pain-control measure in hospitalized patients receiving systemic narcotic medication In r and omized controlled trials , no single definition of response is ideal for all purpose s. We propose a method to present in a simple fashion the likelihood of response over a full range of response levels , which will facilitate a better underst and ing of clinical trial data . We present the technique called the  cumulative proportion of responders analysis  ( CPRA ) and its application to four pain clinical trial data sets as examples . The CPRA can be used to present the proportion of responders over the entire range of possible cut-off points as a graph . This allows the reader to compare treatment groups at any responder level that is valid for their patient population . Whether as a primary or secondary approach to a clinical trial of pain therapy , the display of data in a CPRA format may be useful in the underst and ing of results and applicability to patient care Although nonsteroidal antiinflammatory drugs ( NSAIDs ) improve postoperative pain relief after cesarean delivery , they carry potential side effects ( e.g. , bleeding ) . Perioperative cyclooxygenase (COX)-2 inhibitors show similar analgesic efficacy to nonsteroidal antiinflammatory drugs in many surgical models but have not been studied after cesarean delivery . We design ed this r and omized double-blind study to determine the analgesic efficacy and opioid-sparing effects of valdecoxib after cesarean delivery . Healthy patients undergoing elective cesarean delivery under spinal anesthesia were r and omized to receive oral valdecoxib 20 mg or placebo every 12 h for 72 h postoperatively . As a result of cyclooxygenase-2 inhibitors safety concerns that became apparent during this study , the study was terminated early after evaluating 48 patients . We found no differences in total analgesic consumption between the valdecoxib and placebo groups ( 121 ± 70 versus 143 ± 77 morphine mg-equivalents , respectively ; P = 0.26 ) . Pain at rest and during activity were similar between the groups despite adequate post hoc power to have detected a clinical ly significant difference . There were also no differences in IV morphine requirements , time to first analgesic request , patient satisfaction , side effects , breast-feeding success , or functional activity . Postoperative pain was generally well controlled . Adding valdecoxib after cesarean delivery under spinal anesthesia with intrathecal morphine is not supported at this time Background : Central pain in multiple sclerosis ( MS ) is common and often refractory to treatment . Methods : We conducted a single-center , 5-week ( 1-week run-in , 4-week treatment ) , r and omized , double-blind , placebo-controlled , parallel-group trial in 66 patients with MS and central pain states ( 59 dysesthetic , seven painful spasms ) of a whole-plant cannabis-based medicine ( CBM ) , containing delta-9-tetrahydrocannabinol : cannabidiol ( THC : CBD ) delivered via an oromucosal spray , as adjunctive analgesic treatment . Each spray delivered 2.7 mg of THC and 2.5 of CBD , and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours . Results : Sixty-four patients ( 97 % ) completed the trial , 34 received CBM . In week 4 , the mean number of daily sprays taken of CBM ( n = 32 ) was 9.6 ( range 2 to 25 , SD = 6.0 ) and of placebo ( n = 31 ) was 19.1 ( range 1 to 47 , SD = 12.9 ) . Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale . CBM was superior to placebo in reducing the mean intensity of pain ( CBM mean change −2.7 , 95 % CI : −3.4 to −2.0 , placebo –1.4 95 % CI : −2.0 to −0.8 , comparison between groups , p = 0.005 ) and sleep disturbance ( CBM mean change –2.5 , 95 % CI : −3.4 to −1.7 , placebo –0.8 , 95 % CI : −1.5 to −0.1 , comparison between groups , p = 0.003 ) . CBM was generally well tolerated , although more patients on CBM than placebo  reported dizziness , dry mouth , and somnolence . Cognitive side effects were limited to long-term memory storage . Conclusions : Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Background : Ketamine potentiates intravenous or epidural morphine analgesia . The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain . Methods : Forty-nine patients scheduled to undergo open thoracotomy were r and omly assigned to receive one of two anesthesia regimens : continuous epidural infusion of ropivacaine and morphine , along with intravenous infusion of ketamine ( 0.05 mg · kg−1 · h−1 [ approximately 3 mg/h ] , ketamine group , n = 24 ) or placebo ( saline , control group , n = 25 ) . Epidural analgesia was continued for 2 days after surgery , and infusion of ketamine or placebo was continued for 3 days . Pain was assessed at 6 , 12 , 24 , and 48 h after surgery . Patients were asked about their pain , abnormal sensation on the wound , and inconvenience in daily life at 7 days and 1 , 3 , and 6 months after surgery . Results : The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group ( pain at rest , 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13 ; pain on coughing , 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18 , mean ± SD ; P = 0.002 and P = 0.01 , P < 0.0001 and P = 0.02 , respectively ) . The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group ( 0.5 [ 0–4 ] vs. 2 [ 0–5 ] and 0 [ 0–5 ] vs. 1.5 [ 0–6 ] , median [ range ] , respectively ; P = 0.02 ) . Three months after surgery , a higher number of control patients were taking pain medication ( 2 vs. 9 ; P = 0.03 ) . Conclusions : Very-low-dose ketamine ( 0.05 mg · kg−1 · h−1 ) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks , the only controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion failed to discern any clinical ly relevant benefits . For this study , we used a larger dose of clonidine in an attempt to improve analgesia . Patients ( n = 20 ) undergoing moderately painful orthopedic surgery of the shoulder received an  interscalene brachial plexus block ( 40 mL of mepivacaine 1.5 % , epinephrine 2.5 & mgr;g/mL , and clonidine 50 & mgr;g ) and a perineural catheter before surgery . After surgery , ropivacaine 0.2 % or ropivacaine 0.2 % plus clonidine 2 & mgr;g/mL was delivered via the catheter for 3 days ( basal rate , 5 mL/h ; patient-controlled bolus , 5 mL ; lockout , 1 h ) . Investigators and patients were blind to r and om group assignment . The primary outcome variable was design ated as the most intense pain during the day after surgery . Secondary end-points included additional pain scores , patient-controlled bolus doses , oral analgesic use , sleep quality , and catheter- or infusion-related complications . There were no statistically significant differences between groups for any of the variables investigated . We conclude that adding clonidine 2 & mgr;g/mL to a ropivacaine interscalene perineural infusion does not decrease breakthrough pain intensity the day after surgery . For the additional end-points , our negative findings are only suggestive of a lack of effect and require further study for verification Background : Neuropathic pain in spinal cord injury is a common challenging therapeutic condition . The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine . Methods : Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were r and omized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min . Twelve patients reported evoked pain , and 12 patients had no evoked pain . Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing . Results : Lidocaine significantly reduced spontaneous pain in all patients ( P < 0.01 ) and in each of the two groups with ( P < 0.01 ) and without ( P = 0.048 ) evoked pain , with no difference in number of responders ( pain reduction ≥ 33 % ) between the patients with ( n = 6 ) and without ( n = 5 ) evoked pain . Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia , pinprick hyperalgesia , or pain evoked by repetitive pinprick . Conclusions : Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain . Results are consistent with a central -acting effect of sodium channel blockers acting on neuronal hyperexcitability . Agents ( such as anticonvulsants or antiarrhythmics ) with sodium channel – blocking properties may be a treatment option for spinal cord injury pain BACKGROUND : Gabapentin , an oral non-opioid analgesic , has been used to decrease pain after a variety of surgical procedures . We hypothesized that premedication with gabapentin would minimize tourniquet-related pain in patients receiving IV regional anesthesia ( IVRA ) . METHODS : Patients undergoing elective h and surg 
    Output:
    
agent
Our review revealed a great heterogeneity in definition , format , and values of what is considered a clinical ly relevant difference in pain in RCTs of analgesics , and st and ardizations are advisable
***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 Autologous bone graft is the so-called gold st and ard for reconstruction of bone defects and nonunions . The most frequent complication is donor site pain . The iliac crest is a common source for autologous bone graft . The purpose of this study was to determine whether a continuous infusion of 0.5 % bupivacaine into the iliac crest harvest site provides pain relief that is superior to the relief provided by systemic narcotic pain medication alone in patients undergoing reconstructive orthopaedic trauma procedures . METHODS A prospect i ve , double-blind r and omized study of patients over eighteen years of age who were undergoing harvesting of iliac crest bone graft was conducted . The patients were r and omized to the treatment arm ( bupivacaine infusion pump ) or the placebo arm . Postoperatively , all study patients received morphine sulfate with use of a patient-controlled analgesia pump . The patients recorded the pain at the donor and recipient sites with use of a scale ranging from 0 to 10 . The use of systemic narcotic medication was recorded . Independent- sample s t tests were used to assess differences in perceived pain relief between the treatment and control groups at zero , eight , sixteen , twenty-four , thirty-two , forty , and forty-eight hours after surgery . Pain was also assessed at two and six weeks postoperatively . RESULTS Sixty patients were enrolled . Across all data points , except pain at the recipient site at twenty-four hours , no significant differences in the perception of pain were found between the bupivacaine group and the placebo group . On the average , patients in the treatment group reported more pain than those in the control group . No significant difference was found between the two groups with regard to the amount of narcotic medication used . CONCLUSIONS No difference in perceived pain was found between the groups . The results of this small , unstratified study indicate that continuous infusion of bupivacaine at iliac crest bone-graft sites during the postoperative period is not an effective pain-control measure in hospitalized patients receiving systemic narcotic medication In r and omized controlled trials , no single definition of response is ideal for all purpose s. We propose a method to present in a simple fashion the likelihood of response over a full range of response levels , which will facilitate a better underst and ing of clinical trial data . We present the technique called the  cumulative proportion of responders analysis  ( CPRA ) and its application to four pain clinical trial data sets as examples . The CPRA can be used to present the proportion of responders over the entire range of possible cut-off points as a graph . This allows the reader to compare treatment groups at any responder level that is valid for their patient population . Whether as a primary or secondary approach to a clinical trial of pain therapy , the display of data in a CPRA format may be useful in the underst and ing of results and applicability to patient care Although nonsteroidal antiinflammatory drugs ( NSAIDs ) improve postoperative pain relief after cesarean delivery , they carry potential side effects ( e.g. , bleeding ) . Perioperative cyclooxygenase (COX)-2 inhibitors show similar analgesic efficacy to nonsteroidal antiinflammatory drugs in many surgical models but have not been studied after cesarean delivery . We design ed this r and omized double-blind study to determine the analgesic efficacy and opioid-sparing effects of valdecoxib after cesarean delivery . Healthy patients undergoing elective cesarean delivery under spinal anesthesia were r and omized to receive oral valdecoxib 20 mg or placebo every 12 h for 72 h postoperatively . As a result of cyclooxygenase-2 inhibitors safety concerns that became apparent during this study , the study was terminated early after evaluating 48 patients . We found no differences in total analgesic consumption between the valdecoxib and placebo groups ( 121 ± 70 versus 143 ± 77 morphine mg-equivalents , respectively ; P = 0.26 ) . Pain at rest and during activity were similar between the groups despite adequate post hoc power to have detected a clinical ly significant difference . There were also no differences in IV morphine requirements , time to first analgesic request , patient satisfaction , side effects , breast-feeding success , or functional activity . Postoperative pain was generally well controlled . Adding valdecoxib after cesarean delivery under spinal anesthesia with intrathecal morphine is not supported at this time Background : Central pain in multiple sclerosis ( MS ) is common and often refractory to treatment . Methods : We conducted a single-center , 5-week ( 1-week run-in , 4-week treatment ) , r and omized , double-blind , placebo-controlled , parallel-group trial in 66 patients with MS and central pain states ( 59 dysesthetic , seven painful spasms ) of a whole-plant cannabis-based medicine ( CBM ) , containing delta-9-tetrahydrocannabinol : cannabidiol ( THC : CBD ) delivered via an oromucosal spray , as adjunctive analgesic treatment . Each spray delivered 2.7 mg of THC and 2.5 of CBD , and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours . Results : Sixty-four patients ( 97 % ) completed the trial , 34 received CBM . In week 4 , the mean number of daily sprays taken of CBM ( n = 32 ) was 9.6 ( range 2 to 25 , SD = 6.0 ) and of placebo ( n = 31 ) was 19.1 ( range 1 to 47 , SD = 12.9 ) . Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale . CBM was superior to placebo in reducing the mean intensity of pain ( CBM mean change −2.7 , 95 % CI : −3.4 to −2.0 , placebo –1.4 95 % CI : −2.0 to −0.8 , comparison between groups , p = 0.005 ) and sleep disturbance ( CBM mean change –2.5 , 95 % CI : −3.4 to −1.7 , placebo –0.8 , 95 % CI : −1.5 to −0.1 , comparison between groups , p = 0.003 ) . CBM was generally well tolerated , although more patients on CBM than placebo  reported dizziness , dry mouth , and somnolence . Cognitive side effects were limited to long-term memory storage . Conclusions : Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Background : Ketamine potentiates intravenous or epidural morphine analgesia . The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain . Methods : Forty-nine patients scheduled to undergo open thoracotomy were r and omly assigned to receive one of two anesthesia regimens : continuous epidural infusion of ropivacaine and morphine , along with intravenous infusion of ketamine ( 0.05 mg · kg−1 · h−1 [ approximately 3 mg/h ] , ketamine group , n = 24 ) or placebo ( saline , control group , n = 25 ) . Epidural analgesia was continued for 2 days after surgery , and infusion of ketamine or placebo was continued for 3 days . Pain was assessed at 6 , 12 , 24 , and 48 h after surgery . Patients were asked about their pain , abnormal sensation on the wound , and inconvenience in daily life at 7 days and 1 , 3 , and 6 months after surgery . Results : The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group ( pain at rest , 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13 ; pain on coughing , 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18 , mean ± SD ; P = 0.002 and P = 0.01 , P < 0.0001 and P = 0.02 , respectively ) . The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group ( 0.5 [ 0–4 ] vs. 2 [ 0–5 ] and 0 [ 0–5 ] vs. 1.5 [ 0–6 ] , median [ range ] , respectively ; P = 0.02 ) . Three months after surgery , a higher number of control patients were taking pain medication ( 2 vs. 9 ; P = 0.03 ) . Conclusions : Very-low-dose ketamine ( 0.05 mg · kg−1 · h−1 ) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain Although clonidine has been shown to increase the duration of local anesthetic action and prolong postoperative analgesia when included in single-injection nerve blocks , the only controlled investigation of the efficacy of this practice to improve analgesia for continuous perineural local anesthetic infusion failed to discern any clinical ly relevant benefits . For this study , we used a larger dose of clonidine in an attempt to improve analgesia . Patients ( n = 20 ) undergoing moderately painful orthopedic surgery of the shoulder received an  interscalene brachial plexus block ( 40 mL of mepivacaine 1.5 % , epinephrine 2.5 & mgr;g/mL , and clonidine 50 & mgr;g ) and a perineural catheter before surgery . After surgery , ropivacaine 0.2 % or ropivacaine 0.2 % plus clonidine 2 & mgr;g/mL was delivered via the catheter for 3 days ( basal rate , 5 mL/h ; patient-controlled bolus , 5 mL ; lockout , 1 h ) . Investigators and patients were blind to r and om group assignment . The primary outcome variable was design ated as the most intense pain during the day after surgery . Secondary end-points included additional pain scores , patient-controlled bolus doses , oral analgesic use , sleep quality , and catheter- or infusion-related complications . There were no statistically significant differences between groups for any of the variables investigated . We conclude that adding clonidine 2 & mgr;g/mL to a ropivacaine interscalene perineural infusion does not decrease breakthrough pain intensity the day after surgery . For the additional end-points , our negative findings are only suggestive of a lack of effect and require further study for verification Background : Neuropathic pain in spinal cord injury is a common challenging therapeutic condition . The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine . Methods : Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were r and omized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min . Twelve patients reported evoked pain , and 12 patients had no evoked pain . Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing . Results : Lidocaine significantly reduced spontaneous pain in all patients ( P < 0.01 ) and in each of the two groups with ( P < 0.01 ) and without ( P = 0.048 ) evoked pain , with no difference in number of responders ( pain reduction ≥ 33 % ) between the patients with ( n = 6 ) and without ( n = 5 ) evoked pain . Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia , pinprick hyperalgesia , or pain evoked by repetitive pinprick . Conclusions : Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain . Results are consistent with a central -acting effect of sodium channel blockers acting on neuronal hyperexcitability . Agents ( such as anticonvulsants or antiarrhythmics ) with sodium channel – blocking properties may be a treatment option for spinal cord injury pain BACKGROUND : Gabapentin , an oral non-opioid analgesic , has been used to decrease pain after a variety of surgical procedures . We hypothesized that premedication with gabapentin would minimize tourniquet-related pain in patients receiving IV regional anesthesia ( IVRA ) . METHODS : Patients undergoing elective h and surg 
    Output:
    