***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 
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    Input: PURPOSE A prospect i ve , double-blind study was undertaken to evaluate the effect of using a buffered lidocaine solution on the perception of pain experienced by a patient during its intradermal injection . PATIENTS AND METHODS One hundred fifty patients undergoing diagnostic angiographic and interventional procedures at the authors ' institution were r and omly assigned to receive a 1-mL aliquot of one of three lidocaine solutions : plain 1 % lidocaine , 1 % lidocaine diluted with normal saline in a 10:1 ratio , and 1 % lidocaine diluted with 8.4 % sodium bicarbonate in a 10:1 ratio . The lidocaine solutions were administered intradermally over 10 - 15 seconds . A numerical value was placed on the patient 's perception of pain , separate from that associated with the 25-gauge needle insertion , with use of a linear visual analog scale . RESULTS Mean pain scores were as follows : for the 1 % lidocaine solution , 2.83 + /- 2.60 ; for 1 % lidocaine plus normal saline solution , 2.89 + /- 2.34 ; and for 1 % lidocaine plus sodium bicarbonate solution , 1.37 + /- 1.73 ( P = .0018 ) . CONCLUSION Buffering lidocaine significantly decreased the discomfort associated with its administration as a local anesthetic & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies We performed a r and omized double-blind case – control study in 64 consecutive patients undergoing open carpal tunnel decompression under local anaesthetic  to assess the pain experienced on injection of plain lidocaine ( pH 6.4 ) compared with lidocaine buffered with sodium bicarbonate ( pH 7.4 ) . The results showed no statistical difference in the pain scores reported by patients . The mean pain scores for all patients were low , and most patients reported that they were “ not at all anxious ” about receiving a similar injection in the future Local anesthetics can produce pain during skin infiltration . We design ed a r and omized , prospect i ve trial to determine whether needle gauge and /or solution pH affect pain during the intradermal infiltration of lidocaine . After approval by our institution 's human studies review board , 40 healthy adult volunteers gave their consent to participate in this study . All of the volunteers r and omly received four intradermal injections . Each volunteer was blinded as to the content of the intradermal injections and to which needle size was used for each injection . Each volunteer r and omly received a 0.25-mL intradermal injection of the following four solutions : 1 ) lidocaine 2 % administered through a 25-gauge needle ( lido-25 ) ; 2 ) lidocaine 2 % mixed with sodium bicarbonate ( 4 mL of 2 % lidocaine plus 1 mL of sodium bicarbonate , pH 7.26 ) administered through a 25-gauge needle ( lido-bicarb-25 ) ; 3 ) lidocaine 2 % administered through a 30-gauge needle ( lido-30 ) ; and 4 ) lidocaine 2 % mixed with sodium bicarbonate ( 4 mL of 2 % lidocaine plus 1 mL of sodium bicarbonate ) administered through a 30-gauge needle ( lido-bicarb-30 ) . In each patient , the injection site was in the same region for each of the four injections . The skin wheal was tested for appropriate anesthesia using a 19-gauge needle on the skin wheal . A visual analog pain score was recorded after each intradermal injection . The pain scores were significantly higher in the lido-25 ( 3.2 + /- 0.2 ) group than in the lido-30 ( 2.5 + /- 0.3 ) , lido-bicarb-25 ( 1.9 + /- 0.2 ) , and lido-bicarb-30 ( 1.3 + /- 0.2 ) groups . The lido-bicarb-30 injection was also rated as less painful than the lido-30 injection . We found no differences between the lido-bicarb-25 and the lido-bicarb-30 injections . Complete analgesia for the 19-gauge needle pain stimulus was achieved in all patients for each injection . We conclude that , overall , the pain intensity of an intradermal injection of 2 % lidocaine is low . The addition of sodium bicarbonate to 2 % lidocaine decreases the pain associated with an intradermal skin wheal , and although the use of a 30-gauge needle decreases the pain of injection , the addition of sodium bicarbonate seems to have a greater overall effect than needle size . Implication s : Forty volunteers r and omly received four intradermal injections consisting of 2 % lidocaine with or without sodium bicarbonate via a 25- or 30-gauge needle . The addition of bicarbonate had a greater overall effect than needle size in decreasing the pain associated with the intradermal injection of lidocaine . ( Anesth Analg 1998;86:379 - 81 Bicarbonate buffering of local anaesthetics is known to significantly decrease the pain of their administration and yet few practising surgeons do so . A double-blind r and omised cross-over clinical trial was conducted to confirm the practicality and efficacy of bicarbonate buffering of lignocaine with adrenaline in the setting of a busy local anaesthetic operating theatre . 40 patients received either buffered or control local anaesthetic solutions  in equivalent sites on opposite sides of the body . The pain of each injection was rated from 0 ( no pain ) to 10 ( extreme pain ) . The mean pain score for the buffered solution was significantly lower than the control solution ( 3.06 vs 4.34 , P = 0.002 ) . Bicarbonate buffering of lignocaine with adrenaline is effective , inexpensive and simple ; its widespread use should be encouraged The purpose of this study was to vali date the changes in acute pain measurement scales that are most strongly associated with a patient-determined indicator of clinical importance . Measures of pain intensity and pain relief are commonly used outcomes in therapeutic clinical trials . Recent studies of the properties of acute pain measures have provided data defining the cut-off points that are best associated with clinical ly important differences . Validation of these findings in another clinical trial data set is important . Data were obtained from the titration phase of a recently conducted r and omized controlled clinical trial of oral transmucosal fentanyl citrate ( OTFC ) , which compared OTFC to immediate release morphine sulfate ( MSIR ) for the treatment of cancer-related acute breakthrough pain .  Changes in pain intensity and pain relief were recorded every 15 minutes for 60 minutes and global medication performance recorded at the end of each study pain episode . At any titration step , if the patient felt that the first dose of the study medication did not provide adequate relief within 30 minutes , an additional rescue medication could be taken . To find the level of each pain scale best associated with this measure of the adequacy of pain relief , the calculated sensitivity , specificity , and accuracy for different cut-off points of the measured pain scales were compared to whether or not the patient needed rescue medication . The overall ability of the pain measures to discriminate episodes for which a rescue was not needed was calculated using area under the receiver operating characteristics ( ROC ) curves . Data were analyzed from 134 OTFC-naive patients who collected data on 1307 episodes of breakthrough pain . Using the criteria of a balanced sensitivity and specificity , the best cut-off points were determined to be : 33 % for the percent pain intensity difference ; > or = 2 for the raw pain intensity difference on a 0 - 10 numeric rating scale ; > or = 2 ( i.e. , moderate or better ) for pain relief ; > or = 33 % for the percent maximum total pain relief ; and > or = 2 ( good or better ) for global medication performance . ROC area under the curve ranged from 0.839 to 0.862 for each of the pain measures listed above , calculated at 60 minutes . These data indicate that the pain scale cut-off points that are best associated with a patient-derived measure of a clinical ly important difference closely approximate those found in an earlier study . ROC analysis provided evidence that the overall pain measures were strongly associated with not requiring an " additional dose of rescue medication . " Thus , the cut-off points determined for these pain scales provide a good surrogate measure of a patient-determined clinical ly important response . This provides support for the usefulness of these values in future clinical trials of pain therapy STUDY OBJECTIVE To determine the impact of administration rate and buffering on the pain associated with subcutaneous infiltration of lidocaine . METHODS Forty-two adult volunteers employed at a tertiary care center participated in this prospect i ve , single-blinded study . Each subject received four lidocaine injections prepared and administered as follows : slow , buffered ( SB ) ; slow , unbuffered ( SU ) ; rapid , buffered ( RB ) ; rapid , unbuffered ( RU ) . Buffering was accomplished by mixing 1 % lidocaine with 8.4 % sodium bicarbonate in a 9:1 ratio . Slow administration was 30 seconds and rapid was 5 seconds . Needle size ( 27-gauge ) , injection depth ( .25 inch ) , lidocaine volume ( 1.0 mL ) , and temperature ( room ) were the same for each of the four injections . In all four conditions , the needle remained in the forearm for 30 seconds , to ensure blinding . The main outcome measure was the mean pain score for each condition , as recorded on a 10-cm visual analog scale . RESULTS The lowest pain scores ( mean + /- SE ) were recorded for the SU and SB conditions at 1.49 + /- 29 and 1.48 + /- 26 , respectively , and they were significantly lower than the scores for RB ( 2.34 + /- 28 ; P < .01 ) or RU ( 3.11 + /- 33 ; P < .001 ) . Each of the slow conditions was reported to be the " least painful " of the four significantly more often than either rapid condition . CONCLUSION This is the largest blinded study to assess administration rate and the pain of a local anesthetic . We found that administration rate had a greater impact on the perceived pain of lidocaine infiltration than did buffering One hundred adult day-case patients who required intravenous access had cannulae inserted using local anaesthesia with 1 % lignocaine , 1 % lignocaine with adrenaline or the corresponding pH-adjusted solutions . The local anaesthetic solutions were modified by the addition of 1 ml 8.4 % sodium bicarbonate to 10 ml lignocaine .  Pain scores at different stages of cannulation were noted and showed a significant reduction after use of pH-adjusted solutions ( p less than 0.02 for the plain lignocaine , and less than 0.001 for the lignocaine with adrenaline ) . Modification of the pH of lignocaine solutions by the addition of sodium bicarbonate is a simple method significantly to reduce the discomfort caused by the infiltration of the local anaesthetic & NA ; The purpose of this study was to determine the levels of change on st and ard pain scales that represent clinical ly important differences to patients . Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious . Differences between groups , as summarized by a change in mean values over time , can be difficult to apply to clinical care . Baseline scores vary widely and group mean differences could reflect large changes in a few patients , small changes in many patients , or any combination of these outcomes . Determination of the proportion of patients who have a clinical ly important improvement in 
    Output:
    
CONCLUSIONS Our systematic review suggests that the use of buffered local anesthetics seems to be associated with a statistical decrease in pain of infiltration when compared with unbuffered local anesthetic