***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 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 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 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 & NA ; A prospect i ve double‐blind r and omized trial was conducted on 184 cancer patients with moderate to severe chronic pain to evaluate the analgesic efficacy and tolerability of diclofenac alone ( 50 mg q.i.d . ) or in combination with a weak opioid ( codeine 40 mg q.i.d . ) , or with an anti‐depressant ( imipramine , 10 or 25 mg t.i.d . ) . All demographic and clinical characteristics including cancer type , presence of bone metastases , baseline pain severity , neuropathic and nociceptive pain , and depressive state , were well balanced between the three treatment groups . The main analysis of the study was on the VAS scores at visit 2 ( day 4 ) . The mean VAS values for both associations imipramine plus diclofenac and codeine plus diclofenac were similar to the association placebo plus diclofenac . Patients on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn mainly for inadequate efficacy , while patients on codeine plus diclofenac discontinued equally for inadequate efficacy or adverse events . In conclusion , in a short‐term evaluation the addition of a tricyclic anti‐depressant or a weak opioid to diclofenac did not provide further analgesia with respect to diclofenac administration alone 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 BACKGROUND Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner . This study was design ed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer , a nitric oxide donor , as coadjuvants to oral morphine in cancer pain therapy . METHODS After institutional approval and informed patient consent were obtained , 60 patients with cancer pain were r and omized to one of four groups ( n = 15 ) and studied prospect ively to evaluate analgesia and any adverse effects . A visual analog scale that consisted of a 10-cm line with 0 representing " no pain at all " and 10 representing " the worst possible pain " was introduced . All patients were regularly taking oral amitriptyline 50 mg at bedtime . The morphine regimen was adjusted individually to a maximal oral dose of 80 - 90 mg/day to keep the visual analog scale score less than 4 . When patients reported pain ( visual analog scale of 4 or more ) , despite taking 80 - 90 mg oral morphine daily , the test drug was added as follows : the control group ( CG ) received an additional 20 mg oral morphine ( 10 mg at 12-h intervals ) ; the nitroglycerin group ( NG ) received a 5-mg nitroglycerin patch daily ; the ketamine group ( KG ) received 0.5 mg/kg oral ketamine at 12-h intervals ; and the dipyrone group ( DG ) received 500 mg oral dipyrone at 6-h intervals . Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4 . RESULTS The groups were similar with respect to demographic data and visual analog scale pain scores before treatment . The visual analog scale scores after the test drug was introduced were similar among the groups . The daily consumption of oral morphine  was as follows : on day 15 : CG = DG = NG ( P > 0.05 ) , CG > KG ( P = 0.036 ) ; on day 20 : CG > NG = KG ( P < 0.02 ) ( CG > KG , P < 0.005 ; CG > NG , P < 0.02 ) , DG > KG ( P < 0.05 ) ; on day 30 : CG = DG > KG = NG ( P < 0.05 ) . Patients in the CG and DG groups reported somnolence , but patients in the NG and KG groups did not . CONCLUSIONS Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics . In conjunction with their opioid tolerance-sparing function , joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management 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 Summary The analgesic efficacy and tolerability of nimesulide and naproxen were compared in 68 patients with advanced cancer who needed to be treated with nonsteroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO . Patients received either nimesulide 200 mg or naproxen 500 mg twice daily . The analgesic efficacy and tolerability of the 2 drugs appeared to be similar . Both drugs were effective and were associated with a low incidence of adverse reactions BACKGROUND The European Pain in Cancer survey sought to increase underst and ing of cancer-related pain and treatment across Europe . PATIENTS AND METHODS Patients with all stages of cancer participated in a two-phase tele 
    Output:
    
There is no high- quality evidence to support or refute the use of NSAIDs alone or in combination with opioids for the three steps of the three-step WHO cancer pain ladder .
There is very low- quality evidence that some people with moderate or severe cancer pain can obtain substantial levels of benefit within one or two weeks