***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 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 Severe and chronic pain is a dominant feature in most patients with rheumatoid arthritis . Despite optimum doses of st and ard analgesic and anti-inflammatory drugs , there are many patients who do not obtain adequate pain relief . Until recently , the use of strong analgesics has been strongly contraindicated , as all such available drugs were classified under the Dangerous Drugs Act ( DUdley Hart , 1968 ) . The risk of drug dependence in patients with a chronic disease such as rheumatoid arthritis clearly precludes the use of such drugs except in exceptional circumstances . The development of a new group of narcotic antagonists with a benzomorphan nucleus ( Archer , Albertson , Harris , Pierson , Bird , Keats , Telford , and Papadopoulos , 1962 ) led to the introduction of pentazocine in 1967 . When given by intramuscular or subcutaneous injection , 30 mg . pentazocine is approximately equinanalgesic with 10 mg . morphine ( British Medical Journal , Today 's Drugs , 1970 ) . The W.H.O. Expert Committee on Drug Dependence have passed pentazocine as being safe for use without special controls on three occasions ( W.H.O. Technical Reports , 1966 , 1969 , 1970 ) . It has been widely used for the relief of postoperative pain ( Kantor , Sunshine , Laska , Meisner , and Hopper , 1966 ) in the management of patients with malignant dis-ase ( Beaver , Wallenstein , Houde , and Rogers , 1968 ; Frankendal and Kjellgren , 1971 ) , ischaemic heart ( Scott and Orr , 1969 ) and limb pain ( Taylor , 1971 ) , and in obstetric practice ( Mitchell , 1963 ; Filler and Filler , 1966 ) . In two uncontrolled trials ( Vignon , Chapuy , and Falconnet , 1969 ; DavidChausse and Laporte , 1970 ) , it was suggested that injections of pentazocine in doses ranging from 30 to 120 mg . per day were highly effective in patients with a variety of rheumatic diseases . The marketing of an oral preparation in 1969 made it possible to consider the use of pentazocine as a practical possibility in the long-term management of rheumatoid arthritis , although it was found to be only one-third as effective as the parenteral preparation on clinical assessment ( Beaver , 1968 ) and on monitoring blood levels ( Beckett , Taylor , and Kourounakis , 1970 ) . In considering the use of pentazocine for the treatment of rheumatoid arthritis , it is unlikely that it would be an effective form of therapy on its own . It possesses no anti-inflammatory or antipyretic activity ( Sterling Winthrop Laboratories , Unpublished observations ) . Fremont-Smith and Bayles ( 1965 ) showed that even large doses of pethidine were less effective than salicylates in relieving symptoms in active rheumatoid arthritis , and it is generally accepted that , if adequate analgesia is to be obtained , drugs combining peripheral anti-inflammatory , analgesic , and antipyretic effects must be employed ( Winter , 1966 ; Drug Ther . Bull . , 1966 ) . In this paper , we report the results of a doubleblind cross-over trial in which oral pentazocine and identical placebo tablets were given to patients who were receiving st and ard and stable regimes of nonsteroidal analgesic anti-inflammatory drugs but were obtaining inadequate relief of pain A series of experiments has been carried out with single doses of simple analgesics in patients with rheumatoid arthritis using a consistent polyad design . This method proved to be both valid and useful . Pain relief scores were a better measure of the effectiveness of analgesics than preference .  Aspirin , Codis , and Distalgesic were the most effective analgesics tested , with paracetamol , pentazocine , and Ciba 44,328 intermediate between these agents and placebo . Placebo given after an active analgesic was more effective than when given before ; this phenomenon was not abolished by telling the patients that apparently identical tablets were , in fact , different or by making them different in colour . The effectiveness of soluble placebo  depended on its colour , red being the most effective 
    Output:
    
There was no difference between opioids and placebo in net efficacy after adjustment for AE .
Based on 11 heterogeneous studies of short duration and high risk of bias , there is weak evidence that opioids are effective analgesics in RA .