***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: BACKGROUND The purpose of this r and omized double-blind study was to compare the efficacy and safety of propacetamol 2 g ( an i.v . acetaminophen 1 g formulation ) administered as a 2-min bolus injection ( n=50 ) or a 15-min infusion ( n=50 ) with oral acetaminophen 1 g ( n=50 ) or placebo ( n=25 ) for analgesia after third molar surgery in patients with moderate to severe pain after impacted third molar removal . METHODS All patients were evaluated for efficacy during the initial 6 h period after treatment administration ( T(0 ) ) and for safety during the entire week after T(0 ) . RESULTS The onset of analgesia after propacetamol was shorter ( 3 min for bolus administration , 5 min for 15-min infusion ) than after oral acetaminophen ( 11 min ) . Active treatments were significantly better for all parameters ( pain relief , pain intensity , patient 's global evaluation , duration of analgesia ) than placebo ( P<0.05 ) . Adverse events were more frequent after propacetamol , especially pain at the injection site . Propacetamol bolus result ed in a much higher incidence of local adverse events than the infusion ( propacetamol bolus 90 % vs propacetamol infusion 52 % ) with no clinical ly significant benefits in terms of analgesic efficacy . CONCLUSION I.V. propacetamol , administered as a 15-min infusion , is a fast-acting analgesic agent . It is more effective in terms of onset of analgesia than a similar dose of oral acetaminophen Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed Nonsteroidal anti‐inflammatory drugs ( NSAIDs ) such as aspirin , ibuprofen , and indomethacin ( INN , indometacin ) inhibit both the constitutive ( COX‐1 ) and inducible ( COX‐2 ) isoforms of cyclooxygenase . The induction of COX‐2 after inflammatory stimuli has led to the hypothesis that COX‐2 inhibition primarily accounts for the therapeutic properties of NSAIDs This study aim ed to evaluate whether pre-emptive analgesia modifies the tissue expression of tumour necrosis factor alpha ( TNF-α ) and interleukin 1 beta ( IL-1β ) , and whether there is an association with postoperative surgical outcomes . A triple-blind , r and omized ,  placebo-controlled study of patients undergoing m and ibular third molar removal was performed . Volunteers were allocated r and omly to receive etoricoxib 120 mg , ibuprofen 400 mg , or placebo 1h before surgery . Twenty-four surgical sites per group were required ( 95 % confidence level and 80 % statistical power ) . Pain scores differed significantly between groups ( P<0.001 ) . Etoricoxib and ibuprofen  reduced pain scores compared to placebo ( P<0.05 ) . Pain scores peaked at 4h postoperative in the experimental groups , but at 2h postoperative in the placebo group ( P<0.05 ) . A significant reduction in TNF-α concentration from time 0 ' to time 30 ' was seen for ibuprofen ( P=0.001 ) and etoricoxib ( P=0.016 ) . The ibuprofen group showed a significant reduction in IL-1β levels from time 0 ' to time 30 ' ( P=0.038 ) . In conclusion , TNF-α and IL-1β levels and the inflammatory events in third molar surgery were inversely associated with the degree of cyclooxygenase 2 selectivity of the non-steroidal anti-inflammatory drugs used pre-emptively . Patients given pre-emptive analgesia showed significant reductions in the clinical parameters pain , trismus , and oedema when compared to the placebo group Abstract Acetaminophen is widely used for pain management as an alternative to NSAIDs and selective COX‐2 inhibitors , but its action at a molecular level is still unclear . We evaluated acetaminophen ’s effect on PG release and the expression patterns of genes related to PG production in a clinical model of tissue injury and acute inflammation . Subjects ( 119 out patients ) received either 1000 mg acetaminophen , 50 mg rofecoxib ( a selective COX‐2 inhibitor ) , 30 mg ketorolac ( a dual COX‐1/COX‐2 inhibitor ) , or placebo before the surgical removal of two impacted m and ibular third molars . Microdialysis was used to collect inflammatory transu date from the surgical site for measurement of PGE2 and TXB2 levels at the site of injury . Biopsies were collected to investigate the expression patterns of genes related to PG production at baseline prior to surgery and at 3 or 24 h following surgery . PGE2 release was suppressed by ketorolac , rofecoxib and acetaminophen compared to placebo at 3 h coincident with increased COX‐2 gene expression in biopsies collected from the surgical site . TXB2 release was suppressed only by ketorolac . COX‐2 gene expression remained elevated at 24 h with continued ketorolac and acetaminophen treatment . COX‐1 gene expression was significantly down‐regulated at 24 h by ketorolac , rofecoxib and acetaminophen . Acetaminophen  suppression of PGE2 without inhibiting TXB2 release , when COX‐2 gene expression is up‐regulated , suggests that acetaminophen is a selective COX‐2 inhibitor in vivo . The up‐regulation of COX‐2 gene and down‐regulation of COX‐1 gene expression suggests that acetaminophen may result in changes in COX‐derived prostanoids with repeated doses Pain after third molar extraction has been considered the most suitable pharmaceutical model to evaluate acute pain . This study aim ed to evaluate the pre-emptive analgesic/anti-inflammatory efficacy of etoricoxib 120 mg following m and ibular third molar surgery . A split-mouth , r and omized , triple-blind , placebo-controlled study was conducted with patients undergoing the surgical removal of m and ibular third molars . All volunteers were allocated r and omly to receive either etoricoxib 120 mg or placebo 1h preoperatively , and inflammatory events were evaluated . An estimated sample of 18 surgical units per group was required based on a pilot study ( 95 % confidence level and 80 % statistical power ) . Rescue medication was analyzed by Kaplan-Meier method through log-rank Mantel-Cox test and Pearson linear correlation ( P<0.05 ) . Pre-emptive etoricoxib reduced postoperative pain scores significantly in comparison to placebo ( P<0.001 ) , with a pain score peak at 6h after surgery ( P<0.001 ) . The mean rescue medication consumption was lower in the etoricoxib group compared to the placebo group over the study period ( P<0.05 ) . There was no statistically significant difference between groups related to swelling and trismus . The pre-emptive administration of etoricoxib 120 mg significantly reduced the postoperative pain intensity and the need for rescue medication , but did not reduce swelling or trismus Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation . It is generally believed that COX‐1 is constitutively expressed , whereas COX‐2 is primarily inducible during inflammation . This study examined the in vivo selectivity of  celecoxib  , a COX‐2 inhibitor , and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators ofin vivo selectivity A model was developed to evaluate mild analgesics in an oral surgery outpatient clinic population . On a reportform , patients recorded starting pain and then pain intensities , relief responses , and side effects hourly for 3 hr after drug administration . The treatments were r and omly allocated to patients on a single‐dose‐only basis , and the double‐blind technique was used . The first of two studies compared codeine 30 mg , aspirin 650 mg , codeine 30 mg with aspirin 650 mg , and placebo in 128 subjects . The second study compared codeine 60 mg , acetaminophen 600 mg , and codeine 60 mg with acetaminophen 600 mg and placebo in 160 subjects .  Time‐effect curves were generated for both pain reliel and pain intensity difference ( PID ) . First‐hour scores , peak scores , and total scores were statistically analyzed by parametric and nonparametric factorial analysis . Both aspirin 650 mg and acetaminophen 600 mg proved superior to placebo ( p < 0.01 ) for all measures of effect with both parametric or nonparametric analyses , while codeine 30 mg was not significantly superior to placebo in any analysis . Codeine 60 mg proved significantly superior to placebo for certain measures of effect when analyzed with the nonparametric model . There was no significant interaction between either aspirin or acetaminophen and codeine 
    Output:
    
Third molar surgeries were found to be associated with different COX-related gene expression patterns .