***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: Study Design . A prospect i ve , r and omized , single ( investigator ) blind , comparative efficacy trial was conducted . Objective . To compare the efficacy of continuous low-level heat wrap therapy ( 40 C , 8 hours/day ) with that of ibuprofen ( 1200 mg/day ) and acetaminophen ( 4000 mg/day ) in subjects with acute nonspecific low back pain . Summary of Background Data . The efficacy of topical heat methods , as compared with oral analgesic treatment of low back pain , has not been established . Methods . Subjects ( n = 371 ) were r and omly assigned to heat wrap ( n = 113 ) , acetaminophen ( n = 113 ) , or ibuprofen ( n = 106 ) for efficacy evaluation , or to oral placebo ( n = 20 ) or unheated back wrap ( n = 19 ) for blinding . Outcome measures included pain relief , muscle stiffness , lateral trunk flexibility , and disability . Efficacy was measured over two treatment days and two follow-up days . Results . Day 1 pain relief for the heat wrap ( mean , 2 ) was higher than for ibuprofen ( mean , 1.51;P = 0.0007 ) or acetaminophen ( mean , 1.32;P = 0.0001 ) . Extended mean pain relief ( Days 3 to 4 ) for the heat wrap ( mean , 2.61 ) also was higher than for ibuprofen ( mean , 1.68;P = 0.0001 ) or acetaminophen ( mean , 1.95;P = 0.0009 ) . Lateral trunk flexibility was improved with the heat wrap ( mean change , 4.28 cm ) during treatment ( P ≤ 0.009 vs acetaminophen [ mean change , 2.93 cm ] , P ≤ 0.001 vs ibuprofen [ mean change , 2.51 cm ] ) . The results were similar on Day 4 . Day 1 reduction in muscle stiffness with the heat wrap ( mean , 16.3 ) was greater than with acetaminophen ( mean , 10.5;P = 0.001 ) . Disability was reduced with the heat wrap ( mean , 4.9 ) , as compared with ibuprofen ( mean , 2.7;P = 0.01 ) and acetaminophen ( mean , 2.9;P = 0.0007 ) , on Day 4 . None of the adverse events were serious . The highest rate ( 10.4 % ) was reported in the ibuprofen group . Conclusion . Continuous low-level heat wrap therapy was superior to both acetaminophen and ibuprofen for treating low back pain 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 Purpose Treatment of patients with chronic low back pain ( CLBP ) aims to reduce disability , improve functional capacity , and participation . Time contingent prescription of analgesics is a treatment modality in CLBP . The impact of analgesics on functional capacity is unknown . Aim of the study was to explore the effect of analgesics on functioning measured by functional capacity evaluation , and self-reported disability in patients with CLBP . Methods Explorative R and omized Placebo-Controlled Clinical Trial was performed in an outpatient pain rehabilitation setting on patients waiting for rehabilitation . Included patients had low back pain lasting > 3 months , visual analogue scale worst pain ≥4.0 cm , and age > 18 years . Outcome measures before ( T0 ) and after treatment ( T1 ) : functional capacity , pain intensity , Rol and Morris Disability Question naire . T1 : global perceived pain relief . Patient characteristics and psychological question naires were assessed . Fifty patients were included in this study and were r and omly assigned to 2 weeks treatment or placebo . Treatment : acetaminophen/tramadol 325 mg/37.5 mg per capsule . Dose : maximum acetaminophen 1,950 mg and tramadol 225 mg per day ; treatment and placebo titrated identically . Compliance and side-effects were monitored . Treatment effects between groups over time were compared . Results One patient ( treatment group ) was lost to follow-up . Forty-nine patients remained in the study . Treatment effects in primary outcomes did not differ significantly between groups . A subgroup of 10 ( 42 % ) patients ( treatment group ) reported global pain relief ( responders ) who reduced self-reported disability ( p < 0.05 ) . Responders had significantly lower catastrophizing scores . Conclusion Overall treatment effects were small and non-significant . A subgroup , however , reported improved functioning as a result of treatment . Responders had lower catastrophizing scores Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in  intracranial hemorrhage  ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart Association and the American College of Cardiology favoring administration of -blockers to patients with cardiac risk 
    Output:
    
There is high- quality evidence that paracetamol has no effect on quality of life , function , global impression of recovery , and sleep quality for all included time periods .
There were also no significant differences between paracetamol and placebo for adverse events , patient adherence , or use of rescue medication .
For chronic LBP , there is very low- quality evidence ( based on a trial that has been retracted ) for no effect of paracetamol ( 1 g single intravenous dose ) on immediate pain reduction .
AUTHORS ' CONCLUSIONS We found that paracetamol does not produce better outcomes than placebo for people with acute LBP , and it is uncertain if it has any effect on chronic LBP