***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: Acetaminophen , ibuprofen , and aspirin are the most commonly used drugs in the United States . Although the frequency of their use has been associated with hypertension , prospect i ve data examining the dose of these drugs and risk of hypertension are lacking . Furthermore , whether certain indications for analgesic use , particularly headache , mediate the association is unclear . We conducted 2 prospect i ve cohort studies among older women 51 to 77 years of age ( n=1903 ) from the Nurses ’ Health Study I and younger women 34 to 53 years of age ( n=3220 ) from the Nurses ’ Health Study II who completed detailed supplemental question naires pertaining to their analgesic use and who did not have hypertension at baseline . We analyzed incident hypertension according to categories of average daily dose of acetaminophen , nonsteroidal anti-inflammatory drugs , and aspirin . Information on indications for analgesic use as well as relevant confounders was also gathered prospect ively . Compared with women who did not use acetaminophen , the multivariable adjusted relative risk for those who took > 500 mg per day was 1.93 ( 1.30 to 2.88 ) among older women and 1.99 ( 1.39 to 2.85 ) among younger women . For nonsteroidal anti-inflammatory drugs , similar comparisons yielded multivariable relative risks of 1.78 ( 1.21 to 2.61 ) among older women and 1.60 ( 1.10 to 2.32 ) among younger women . These associations remained significant among women who did not report headache . Aspirin dose was not significantly associated with hypertension . Higher daily doses of acetaminophen and nonsteroidal anti-inflammatory drugs independently increase the  risk of hypertension in women . Because acetaminophen and nonsteroidal anti-inflammatory drugs are commonly used , they may contribute to the high prevalence of hypertension in the United States Background — Although r and omized trials of cyclooxygenase-2 ( COX-2 ) inhibitors have shown increased cardiovascular risk , studies of nonselective , nonsteroidal antiinflammatory drugs ( NSAIDs ) and acetaminophen have been inconsistent . Methods and Results — We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events ( nonfatal myocardial infa rct ion , fatal coronary heart disease , nonfatal and fatal stroke ) in a prospect i ve cohort of 70 971 women , aged 44 to 69 years at baseline , free of known cardiovascular disease or cancer , who provided medication data biennially since 1990 . During 12 years of follow-up , we confirmed 2041 major cardiovascular events . Women who reported occasional ( 1 to 21 d/mo ) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events . However , after adjustment for cardiovascular risk factors , women who frequently ( ≥22 d/mo ) used NSAIDs had a relative risk ( RR ) for a cardiovascular event of 1.44 ( 95 % CI , 1.27 to 1.65 ) compared with nonusers , whereas those who frequently consumed acetaminophen had a RR of 1.35 ( 95 % CI , 1.14 to 1.59 ) . The elevated risk associated with frequent NSAID use was particularly evident among current smokers ( RR=1.82 ; 95 % CI , 1.38 to 2.42 ) and was absent among never smokers ( Pinteraction=0.02 ) . Moreover , we observed significant dose-response relations : Compared with nonusers , the RRs for a cardiovascular event among women who used ≥15 tablets per week were 1.86 ( 95 % CI , 1.27 to 2.73 ) for NSAIDs and 1.68 ( 95 % CI , 1.10 to 2.58 ) for acetaminophen . Conclusions — Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events , although more moderate use did not confer substantial risk 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 Acetaminophen ( APAP ) is a popular analgesic . In the present study , we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese . Five healthy volunteers were administered 1000 mg of APAP orally . Five patients with chronic pain were administered the optimal oral dose of APAP ranging from 600 to 1000 mg to allow for an adequate analgesic effect . Plasma APAP and APAP metabolite concentrations were measured in the volunteers , plasma APAP concentrations and pain scores using a visual analog scale were measured in the patients with chronic pain . Patient data were fitted to a first-order absorption one-compartment model with delayed effects accounted for by an effect compartment . A sigmoid Emax model was used as the pharmacodynamic model . Acetaminophen-cysteine metabolites , which are conjugates of the toxic metabolite N-acetyl-p-benzoquinone-imine , were detected in the plasma at levels lower than 0.2 microg/ml , but no side effects were observed . The pharmacokinetic and pharmacodynamic parameter ( mean+/-S.D. ) estimates were as follows : clearance , 18.7+/-4.7 l/h ; distribution volume , 30.9+/-6.8 l ; absorption rate constant , 2.4+/-1.3 h(-1 ) ; rate constant for the elimination of APAP  from the effect compartment , 1.3+/-0.5 h(-1 ) ; maximum pain relief score , 4.6+/-2.2 units ; effect compartment concentration at 50 % maximum , 2.0+/-1.2 microg/ml ; and sigmoid factor , 1.3+/-0.7 . These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain & NA ; The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy ( DPN ) . The post hoc analysis is based on a 12 week , multinational , placebo‐controlled trial of pregabalin in which 401 patients were r and omized to treatment . Study measures included the Brief Pain Inventory short‐form ( BPI‐sf ) , EQ‐5D and other patient‐reported outcomes . Cutpoints were derived on the BPI‐sf 0–10 average pain numeric rating scale [ NRS ] to classify pain grade s of “ mild ” ( 1–3 ) , moderate ( 4–6 ) and severe ( 7–10 ) , adjusting for geographical regions where data were collected . Two different metrics were used to classify the importance of change in pain severity from baseline to 12 weeks : changes in pain severity grade s ( defined by cutpoint categories ) and percent reduction in the NRS ( categories ranging from 0–9 % to ≥50 % ) . An improvement in one pain grade or a ≥30 % reduction in the NRS served as determinants of a clinical ly important difference . Patients with a one‐ grade reduction in pain severity , either from “ severe‐to‐moderate ” or “ moderate‐to‐mild , ” had a 3‐point improvement the BPI‐sf Pain Interference Index ( PII ; a composite measure of function ) ; a reduction from “ severe‐to‐mild ” pain corresponded to a 6‐point improvement in the PII . Similarly , a reduction in the NRS of ≥30 % and ≥50 % corresponded to a 3‐point and a 5‐point improvement in the PII , respectively . Changes in pain were also associated with changes in health status . Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinical ly important changes in function and health status A r and omized , controlled , parallel-group clinical trial was carried out in general practice to assess the clinical efficacy of a new back support ( ' Lumbotrain ' ) compared with ' st and ard therapy ' of advice on rest and lifestyle in the treatment of patients with non-specific low back pain . A total of 216 patients entered this study ( 111 ' Lumbotrain ' group , 105 control group ) . All patients were allowed to take 1 g paracetamol up to 4-times daily if necessary for control of pain . Self- assessment s were made daily by patients , over a period of 21 days , of pain levels at rest , on activity , at night , and limitation of activity using visual analogue scales . Details were also recorded of their ability to work or not , and the number of doses of paracetamol taken . At the end of the study period , patients assessed their overall response to treatment and those in the ' Lumbotrain ' group were question ed on the comfort and ease of use of the back support . A clinical examination was carried out by the doctor at the start and end of the study period and an assessment made of the total range of active and passive back movement . Analysis of the daily diary records showed there were progressive , significant reductions in mean scores for all the pain and activity criteria in both groups and these were significantly greater in the ' Lumbotrain ' group from Day 7 onwards . The times taken for reduction of symptom scores to 10 % of initial values were significantly less in the ' Lumbotrain ' group , such a degree of recovery occurring 2 to 4 days more rapidly than in the control group . A significantly higher proportion of patients in the ' Lumbotrain ' group became able to work normally . After 3 weeks , 85 % of patients in the ' Lumbotrain ' group could work normally , as compared with 67 % in the control group ( p less than 0.02 ) . Total analgesic consumption during the trial was significantly lower ( p less than 0.0001 ) in the ' Lumbotrain ' group ( median 24.5 doses ) than in the control group ( median 51 doses ) . Overall clinical assessment scores were significantly superior in the ' Lumbotrain ' group ( p less than 0.002 ) . Improvement was seen in 106 ( 95 % ) of 111 patients in the ' Lumbotrain ' group , as compared with 79 ( 77 % ) of 103 of those in the control group ( p less than 0.0002 ) . ( ABSTRACT TRUNCATED AT 400 WORDS & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate  percentage  pain reduction  for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy 
    Output:
    
There was no evidence from r and omised controlled trials to support or refute the use of paracetamol ( acetaminophen ) to treat chronic non-cancer pain in children and adolescents .
We know from adult r and omised controlled trials that paracetamol , can be effective , in certain doses , and in certain pain conditions ( not always chronic).This means that no conclusions could be made about efficacy or harm in the use of paracetamol ( acetaminophen ) to treat chronic non-cancer pain in children and adolescents