***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 Persistent pain is a challenging clinical problem after breast cancer treatment . After surgery , inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain . Using quantitative sensory testing , we tested the hypothesis that adding COX-2 inhibition to st and ard treatment reduces hyperalgesia after breast cancer surgery . A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia . Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were r and omized to COX-2 inhibition ( 2x40 mg parecoxib on day of surgery , thereafter 2x200 mg celecoxib/day until day five ) or placebo . Preoperatively and 1 , 5 , 15 days and 1 , 3 , 6 , 12 months postoperatively , we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100 mm VAS score for pain . We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication . To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months . Results 48  COX-2 inhibition  and 46 placebo  patients were analyzed in a modified intention to treat analysis . Contrary to our primary hypothesis , change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo . COX-2 inhibition had an effect on pain on movement at postoperative day 5 ( p<0.01 ) . Consistent with our secondary hypothesis , change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain ( p<0.01 ) from day 5 to 1 year postoperatively . Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery . Central sensitization may play a role in the genesis of persistent postsurgical pain In a clinical double-blind study , the analgesic efficacy and the side-effects of nimesulide ( Aulin , CAS 51803 - 78 - 2 ) and naproxen administered to 68 patients affected by advanced cancer pain were compared . Patients were treated with non-steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO . The dose administered was 200 mg b.i.d . ( every 12 h ) for nimesulide and 500 mg b.i.d . ( every 12 h ) for naproxen . From this study the analgesic effect and the tolerability of the two drugs appeared to be similar . Both drugs result ed to be effective with a low incidence of adverse events that may be related to their use The analgesic efficacy of ketorolac tromethamine was compared to placebo in 126 patients suffering moderate or severe chronic pain due to cancer in a double-blind parallel r and omized study . Ketorolac was administered intramuscularly in doses of 10 , 30 or 90 mg . Pain intensity and pain relief were assessed for 6 hours by scoring st and ard verbal scales and an overall assessment of the medication was given by the patients and the observer on completion of the study . Each dose of ketorolac was statistically superior to placebo for the sum of pain intensity difference ( SPID ) but no difference was seen between the three ketorolac regimens . When the ketorolac groups are combined , there was a significantly better pain relief as compared to placebo . The global evaluation scores were also statistically superior in the ketorolac groups combined than in the placebo group . A total of 15 patients reported minor adverse events , 10 being after ketorolac doses . This study shows that single intramuscular doses of ketorolac of 10 mg and above are effective in the relief of cancer pain , and are associated with a low incidence of side-effects Objectives This study aims to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic dose of methadone and /or to improve the level of pain control in oncologic patients . Patients and methods Fifty patients on stable doses of morphine for 1 week were switched to methadone using a “ stop – start ” strategy and r and omized in a double-blind fashion to receive either acetaminophen ( 750 mg PO every 6 hours ) or placebo for a 7-day period . We collected data regarding level of pain , side effects , and quality of life . Results Substitution of morphine for methadone result ed in a significant reduction in constipation ( p < 0.001 ) and xerostomia ( p = 0.03 ) . There was also an improvement in the numeric pain scale ( p = 0.03 ) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 question naire . Addition of acetaminophen did not improve pain control or reduce the time of stabilization of analgesia once methadone was introduced . At the end of the study , most patients ( 70.8 % , p = 0.001 ) preferred methadone to morphine . Conclusions Early switching from morphine to methadone was a safe and efficient strategy for the reduction of side effects and improvement of analgesia , allowing for a comfortable dosing regimen . In this scenario , the association with acetaminophen did not improve pain control or reduce the time to achieve an equianalgesic dose of methadone Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy . Fewer patients using benzydamine rinse required systemic analgesics . All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy . Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration The role of non-steroidal anti-inflammatory drugs ( NSAIDs ) in cancer pain has been well established in the treatment of mild pain and in association with opioids in the treatment of moderate to severe pain . The aim of this study was to verify the effects of NSAIDs on morphine escalation in advanced cancer patients with pain followed-up at home and to assess the pharmacoeconomic implication s. A prospect i ve r and omised controlled study was carried out in 156 consecutive advanced cancer patients with pain followed-up at home in the period December 1999-December 2000 . In this group of patients , 47 were selected with pain progression after 1 week of opioid stabilisation . Patients were r and omly assigned to one of two groups : group ' O ' patients were treated with continuing opioid escalation according to their clinical needs ; group ' OK ' received ketorolac 60 mg/daily orally ( p.o . ) in three doses and then continued opioid escalation according to their clinical situation . Performance status , doses of morphine before and after starting treatment , mean weekly pain intensity ( assessed by means of a numerical scale from 0 to 10 ) , mean weekly symptoms intensity , adverse effects and pain mechanisms were recorded . Moreover , drug costs per day in both groups were calculated . Patients who received ketorolac in addition to morphine showed a better analgesia after a week in comparison to the group treated with morphine only ( P=0.005 ) . Thereafter ,  morphine escalation was slower and the maximum  morphine dose was lower in the group treated with ketorolac . The incidence and the severity of gastric discomfort was more evident in patients treated with ketorolac , while constipation was significantly increased in patients who received morphine only . Drug costs per day were similar in both groups ; statistical differences were observed in patients who started on lower morphine doses ( < 100 mg/daily ) in the two groups ( 4.3 in the ketorolac-morphine group versus 3.4 in the morphine group ; P=0.012 ) . The use of NSAIDs reduces the need for an opioid dose escalation or allows the use of lower doses . Their use is associated with a more intense gastric discomfort , but results in less opioid-related constipation . The eventual additive cost for NSAIDs therapy is negligible , especially in patients taking high doses of morphine In a controlled double blind study of  analgesics for the pain of gastrointestinal cancer ,  aspirin ( 650 mg ) was significantly more effective than placebo and superior to orally used codeine sulfate ( 60 mg ) . The effectiveness of aspirin  was not specific for carcinoma of the pancreas , however , because the same pattern of pain relief was found in colonic carcinoma Introduction Adjunct nonopioid analgesics may improve pain control in patients with cancer needing morphine or its derivates .  Dypirone is a cheap nonopioid analgesic widely used in many countries . Objective The objective of the study was to evaluate , whenever morphine was started , if associating dipyrone with it would improve pain control and if this effect was time dependent . Material s and methods This is a double-blind placebo-controlled r and omized crossover study . Thirty-four ambulatory cancer patients experiencing cancer-related pain for which oral morphine was to be started at the dose of 10 mg orally ( PO ) every 4 h were r and omized to take either dipyrone 500 mg PO every 6 h or placebo . After 48 h , patients would be switched from dipyrone to placebo and vice versa . Pain was the primary outcome and was measured using a visual analogue scale before starting medications , at 48 and 96 h. Results We r and omized 16 patients to start with placebo ( group 1 ) and 18 with dipyrone ( group 2 ) .  Pain scores for groups 1 and 2 were at baseline : 7.31 ± 0.29 vs 6.88 ± 0.28 ( p = 0.3 ) , at 48 h : 7.06 ± 0.32 vs 5.5 ± 0.31 ( p = 0.001 ) , and at 96 h : 3.18 ± 0.39 vs 1.94 ± 0.37 ( p = 0.03 ) . Both groups had significant improvements in pain scores after introducing dipyrone ( p < 0.001 , for both ) . Main toxicities were nausea , vomiting , epigastric pain , and myalgias . Twenty-eight patients chose dipyrone , four placebo , and two were indifferent . Conclusions We conclude that dipyrone adds significantly to the analgesic effect of morphine and , when given at the time of starting morphine , results in better pain scores even after dipyrone is discontinued Objective The present study aim ed to examine the effectiveness of intravenous administration of paracetamol added to morphine in the control of cancer pain and its possible contribution as reduction of opioid consumption and opioid-related side effects . Material s and methods A total of 43 patients with chronic cancer pain without neuropathic origin aged between 18 and 76 years and receiving step 2 treatment according to the World Health Organization analgesic ladder were included . Patients were r and omized to receive intravenous administration of saline ( control ) or 1 g of paracetamol on top of morphine .  Visual analog scale ( VAS ) , patient rating index ( PRI ) , Eastern Cooperative Oncology Group ( ECOG ) status , patient satisfaction , and safety were evaluated . Main results Both treatments result ed in improved VAS and PRI scores compared to baseline . However , groups did not differ in terms of VAS and PRI scores , morphine consumption , side-effect frequencies , laboratory values , ECOG status , and patient satisfaction . Conclusions Although safe and there are signals for a true analgesic efficacy , our results failed to confirm any benefits of add-on treatment with intravenous administration of paracetamol . However , the study was underpowered , and future studies in this important area need to be wary of background noise and the risk of a type II error As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . 
    Output:
    
There was no convincing evidence for satisfactory pain relief by acetaminophen alone or in combination with strong opioids .
We found substantial evidence of moderate quality for a satisfactory pain relief in cancer by non-steroidal anti-inflammatory drugs ( NSAIDs ) , flupirtine , and dipyrone compared with placebo or other analgesics .
There was no evidence for a superiority of one specific non-opioid .
There was moderate quality of evidence for a similar pain reduction by NSAIDs in the usual dosage range compared with up to 15 mg of morphine or opioids of equianalgesic potency .
The combination of NSAID and step III opioids showed a beneficial effect , without a decreased tolerability .
There is scarce evidence concerning the combination of NSAIDs with weak opioids .
Non-steroidal anti-inflammatory drugs , flupirtine , and dipyrone can be recommended for the treatment of cancer pain either alone or in combination with strong opioids .
The use of acetaminophen in the palliative setting can not be recommended .
There is a lack of evidence regarding pain treatment by non-opioids in specific cancer entities