***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: OBJECTIVE This study evaluated the efficacy and tolerability of tramadol 37.5-mg/acetaminophen 325-mg combination tablets ( tramadoUAPAP ) as add-on therapy in subjects with rheumatoid arthritis ( RA ) pain that was inadequately controlled by NSAIDs and disease-modifying antirheumatic drugs alone . METHODS Subjects in this multicenter , double-blind trial were r and omized in a 3:1 ratio to receive 1 tramadol/ APAP tablet TID or a matching placebo for 1 week . Stable doses of previous medications were continued during the study . The primary efficacy variable was the mean daily pain relief score over 1 week , measured on a 6-point scale ( 4 = complete ; ' = a lot ; 2 = some ; 1 = a little ; 0 = none ; -1 = worse ) . Secondary outcomes included the mean daily pain intensity score , measured on a 100-mm visual analog scale ( VAS ) ( from 0 mm = no pain to 100 mm = extreme pain ) ; pain intensity and pain relief at day 7 ; subjects ' and investigators ' mean overall assessment s of study drug , measured on a Likert scale ( from 2 = very good to -2 = very poor ) ; and subjects ' assessment s of 8 aspects of physical function ( measured on the Health Assessment Question naire ) . RESULTS Of 277 subjects r and omized to treatment , 267 ( 201 tramadol/APAP , 66 placebo ) were included in the intent-to-treat population . Mean ( SD ) daily pain relief scores at the end of 1 week were significantly greater in the tramadol/APAP group compared with the placebo group ( 1.04 [ 0.89 ] vs 0.78 [ 0.80 ] , respectively ; P = 0.037 ) , and mean daily pain intensity scores at the end of 1 week were significantly lower ( 47.23 [ 19.96 ] vs 53.81 [ 16.59 ] ; P = 0.018 ) . Physical function at the end of 1 week did not differ significantly between tramadol/APAP and placebo .  Two hundred seventy-two subjects ( 205 tramadol/APAP , 67 placebo )  were evaluable for tolerability . One hundred thirty-three of these subjects had at least 1 adverse event . The incidence of adverse events was significantly higher in the tramadol/APAP group than in the placebo group ( 57.6 % vs 22.4 % ; P < 0.001 ) . Discontinuations due to adverse events occurred in 19.0 % of the tramadol/APAP group and 3.0 % of the placebo group ( P = 0.001 ) . Of 213 treatment-related adverse events in tramadol/APAP subjects , nausea ( 34.1 % ) was the most frequent , followed by dizziness ( 20.0 % ) and vomiting ( 15.6 % ) . One serious adverse event -- chest discomfort , nausea , and vomiting after taking study medication-occurred in a subject receiving tramadol/APAP The symptoms resolved 1 day after discontinuing tramadol/APAP . CONCLUSIONS In this study , tramadol/APAP used as add-on therapy in subjects with symptomatic RA was associated with a significant improvement in pain relief and a significant reduction in pain intensity compared with placebo , with no improvement in physical function . Use of tramadol/APAP may be considered when analgesics are needed in addition to conventional NSAIDs and disease-modifying antirheumatic drugs in subjects with RA A single-blind between-patient study in general practice was made to examine the acceptability and analgesic efficacy of a combination of fenoprofen ( 200 mg ) and paracetamol ( 500 mg ) given 3 to 4 times daily for a period of 4 to 14 days in the treatment of acute and chronic pain . The combination was compared with dihydrocodeine tartrate ( 30 mg ) in two groups of 75 patients suffering from a wide variety of presenting conditions , including osteoarthritis , spondylitis , lumbago , ' sciatica , non-articular rheumatism and trauma . Clinical and patient assessment indicated that the combination was an effective analgesic combination , significantly better in success rate than  dihydrocodeine tartrate  and with a much lower incidence of side-effects ( 13 % of patients receiving fenoprofen and paracetamol reported side-effects compared to 37 % for the dihydrocodeine group ) . The combination demonstrated particular success in the treatment of non-articular rheumatism In order to evaluate the efficacy of central ly acting analgesics . In treating rheumatic diseases , tramadol hydrochloride ( Tramal Grunental ) has been administered to a group of 68 patients ( 36 women and 32 men ) , who received 100 mg twice a day during a 10-day treatment . The testing comprised 14 female patients with rheumatoid arthritis , 20 patients ( 7 women and 13 men ) with degenerative ( OA ) hip and knee diseases and 34 patients ( 15 women and 19 men ) affected by the vertebrogen painful syndrome of lumbar spine . The control group comprised 12 patients ( 9 women and 3 men ) with rheumatoid arthritis using non-steroidal antiinflammatory drugs only , 22 patients ( 12 women and 10 men ) with the OA of the hip and knee , using paracetamol only , and 30 patients ( 15 women and 15 men ) affected by the vertebrogen painful syndrome of lumbar spine , also using paracetamol only . The visual analogue scale has been used in following the pain relief assessment s during the therapy . It has thus been observed that the intensity of pain has not been significantly relieved with the acute rheumatic diseases ( p > 0.05 ) in the control group either ; that the significant pain relief has occurred with the degenerative ( OA ) rheumatic diseases ( p < 0.05 ) but not in the control group ; while the best analgetic effect of tramadol has been proved on the patients affected by the vertebrogen painful syndrome of lumbar spine ( p < 0.01 ) but was not significant in the control group . During the therapeutic treatment 13 patients ( 19 % ) , mostly the elderly , experienced side effects , manifested as nausea and the dry mouth Intraarticular morphine inhibits pain after knee surgery without overt toxicity . This study examined intraarticular morphine in chronic arthritis . We undertook a r and omized double-blind comparison between intraarticular morphine ( 3 mg ) , dexamethasone ( 4 mg ) and saline ( 3 ml ) in 44 patients with chronic inflammatory arthritis or osteoarthritis of the knee .  Pain ( the primary outcome measure ) was assessed at rest and during activity for 6 days using a visual analog scale ( VAS ) and the McGill pain question naire . Before drug injections and on day 6 synovial leukocyte counts ( the secondary outcome measure ) were taken . During the first 6 h after injection both morphine and dexamethasone significantly reduced VAS and pain rating indices ( PRI ) in comparison to saline . Both substances also produced a significant reduction of PRI compared to saline during the subsequent 5 days . No patient displayed untoward side effects . Synovial leukocyte counts were lower after morphine than after saline . In conclusion , intraarticular morphine produces analgesia of similar magnitude to dexamethasone and it may have antiinflammatory actions in chronic arthritis Actions on performance of  dextropropoxyphene ( DXP ) alone and in combination with amitriptyline ( AMI ) , indomethacin ( IN ) , and placebo were compared in 15 patients with rheumatoid arthritis . The patients were on their prescribed maintenance regimen excluding analgesics . In four r and omized test sessions at two-week intervals , they received double blind and crossover single oral doses of DXP 130 mg , IN 50 mg , DXP 65 mg + AMI 25 mg or placebo , each after two days ' pretreatment with the same drug . Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration . DXP impaired critical flicker discrimination , symbol copying and body balance without modifying tracking , choice reactions or attention . It rendered the subjects elated , muzzy , mentally slow and calm . Actions of AMI + DXP were about the same . IN impaired body balance and critical flicker recognition . Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low . We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills . Small doses of AMI may not enhance the mild psychomotor effects of DXP . Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance A double-blind , placebo-controlled , between-patient evaluation of the analgesic properties of oral meptazinol was carried out in 60 patients suffering from chronic pain due to rheumatoid arthritis and osteoarthritis . Patients were allocated , at r and om , to receive either 200 mg meptazinol every 3 to 6 hours as required or identical matching placebo for a total period of 72 hours . Data from 57 patients ( 30 on meptazinol , 27 on placebo )  were suitable for analysis . Pain intensity in five major categories was assessed using a 4-point verbal rating scale by a clinician before the first dose and at the end of the trial period . Patients performed a self- assessment of pain prior to taking the first dose and subsequently at 2,4,24 , 48 and 72 hours using 100 mm visual analogue scales and verbal rating scales . The clinician-rated pain scores showed no significant difference between the two groups in initial pain intensity . After 72-hours ' treatment , there was a significant ( p less than l.01 ) reduction in pain intensity after 2 hours which was maintained throughout the trial period . There was no significant reduction in pain intensity in patients taking placebo .  Visual analogue scale scores and pain intensity difference scores showed significantly ( p less than 0.01 ) greater reduction in pain intensity at all time points in the meptazinol- treated patients . ( ABSTRACT TRUNCATED AT 250 WORDS STUDY OBJECTIVES To examine the effect of three titration schedules on the tolerability of tramadol  , and to determine whether slow titration would reduce the frequency of drug discontinuation due to adverse events . DESIGN Multicenter , outpatient , double-blind , parallel study . SETTING Twenty-eight outpatient study centers . SUBJECTS Four hundred sixty-five patients with chronic joint pain Interventions . Patients were r and omized into one of four treatment groups for 14 days : placebo , or tramadol dosage titrated at 1 , 4 , or 10 days to achieve the study target dosage of 200 mg/day . They continued taking their dosage of nonsteroidal antiinflammatory drug during the study . Each group was examined to determine if slower titration result ed in a statistically significant trend toward fewer discontinuations due to nausea and /or vomiting and dizziness and /or vertigo . Discontinuation due to any adverse event was similarly analyzed . If the trend was statistically significant , pairwise comparisons were performed to determine the statistical significance among titration rates . MEASUREMENTS AND MAIN RESULTS A statistically significant trend was seen toward fewer discontinuations as a result of nausea/vomiting , dizziness/vertigo , and any adverse event as the titration rate decreased . Patients with 10-day titration rate required the fewest discontinuations , and this rate was statistically significantly different from both the 1- and 4-day rates for discontinuations . CONCLUSION A slower rate of initiating tramadol therapy ( 50-mg increments every 3 days ) improved tolerability with significantly fewer discontinuations due to dizziness or vertigo This study evaluated transdermal fentanyl ( TDF ) for the treatment of  pain from rheumatoid arthritis ( RA ) which was not adequately controlled by nonopioid analgesics and /or weak opioids . Following 1 week of optimization of current analgesic medication , patients ( n=104 ) started 28-day treatment with 25 μg/h of TDF , with the option to up-titrate until adequate pain control was achieved . Metoclopramide was taken during the 1st week and as needed thereafter . Eighty-four patients completed the treatment phase , and 42 entered the 1-week tapering-off phase . The most frequently used maximum dose was 25 μg/h . The number of patients with pain control increased , particularly in the 1st week of treatment ( 33 % to 77 % ) , to 88 % on day 28 . From baseline to endpoint , there were reductions in pain ( P<0.001 ) , including in “ pain right now ” at 24 h , and in degree of pain ( mean reduction from “ severe ” to “ moderate ” ) , improvements in function ( majority of items in the Health Assessment Question naire ) ( P<0.001 ) , and in quality of life ( Short Form 36 physical P<0.001 , mental P<0.05 ) . Treatment was assessed favorably : ≥78 % would recommend it . Transdermal fentanyl should be considered in treatment programs for patients with RA Objectives The purpose of the study was to investigate the effectiveness and tolerability of transdermal fentanyl in a treatment regimen in patients with rheumatoid arthritis ( 
    Output:
    
There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA , but adverse effects are common and may offset the benefits of this class of medications .
There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks , or the role of strong opioids