***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: ABSTRACT The time to antibiotic administration ( TTA ) has been proposed as a quality -of-care measure in febrile neutropenia ( FN ) ; however , few data regarding the impact of the TTA on the mortality of adult cancer patients with FN are available . The objective of this study was to determine whether the TTA is a predictor of mortality in adult cancer patients with FN . A prospect i ve cohort study of all consecutive cases of FN , evaluated from October 2009 to August 2011 , at a single tertiary referral hospital in southern Brazil was performed . The TTA was assessed as a predictive factor for mortality within 28 days of FN onset using the Cox proportional hazards model . Kaplan-Meier curves were used for an assessment of the mortality rates according to different TTAs ; the log-rank test was used for between-group comparisons . In total , 307 cases of FN ( 169 subjects ) were evaluated . During the study period , there were 29 deaths . In a Cox regression analysis , the TTA was independently associated with mortality within 28 days ( hazard ratio [ HR ] , 1.18 ; 95 % confidence interval [ CI ] , 1.10 to 1.26 ) ; each increase of 1 h in the TTA raised the risk of mortality within 28 days by 18 % . Patients with FN episodes with a TTA of ≤30 min had lower 28-day mortality rates than those with a TTA of between 31 min and 60 min ( 3.0 % versus 18.1 % ; log-rank P = 0.0002 ) . Early antibiotic administration was associated with higher survival rates in the context of FN . Efforts should be made to ensure that FN patients receive effective antibiotic therapy as soon as possible . A target of 30 min to the TTA should be adopted for cancer patients with FN Background : Early administration of antimicrobial ( AM ) is relevant in children with cancer , fever and neutropenia ( FN ) . The recommendation is to administer the first dose of AM within the first hour of hospital admission . Our aims were to determine the time from the moment that a child with FN is admitted to the hospital until they receive their first dose of AM and to determine the association with clinical outcomes . Methods : This prospect i ve , multicenter study evaluated the time elapsed from the admission to the first dose of AM , comparing this variable by admitting hospital and presentation location ( Emergency Department/Oncology Units ) and evaluating the clinical outcomes by the following variables : days of fever , days of hospitalization , hypotension , transfer to intensive care unit , sepsis and mortality . Results : A total of 226 children with 388 episodes of FN were enrolled from 5 hospitals ( July 2012–April 2014 ) . The median time between hospital admission and administration of the first dose of AM  was 132 minutes ( interquartile range : 60–246 minutes ) . The median time to AM administration was significantly different between hospitals ( 70 vs. 200 minutes , P < 0.0001 ) and between presentation locations ( Emergency Department vs. Oncology Units , median : 200 vs. 100 minutes , P < 0.0001 ) . Twenty-five percentage of children received AM within 1 hour of admission . The administration of AM after 60 minutes was not associated with worse outcomes . Conclusions : Time to AM administration was longer than the recommendation . The findings described provide an opportunity to identify gaps and implement programs aim ed at improving the equity and excellence of care in children with cancer and FN Background Antibiotic delivery to patients with fever and neutropenia ( F&N ) in < 60 min is an increasingly important quality measure for oncology centers , but several published reports indicate that a time to antibiotic delivery ( TTA ) of < 60 min is quite difficult to achieve . Here we report a quality improvement ( QI ) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N. Procedure We used Lean- Methodology and a Plan-Do- Study -Act approach to direct QI efforts and prospect ively tracked TTA measures and associated clinical outcomes ( length of stay , duration of fever , use of imaging studies to search for occult infection , bacteremia , intensive care unit ( ICU ) consultation or admission , and mortality ) . We then performed statistical analysis to determine the impact of our QI interventions on total TTA , sub-process times , and clinical outcomes . Results Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in < 60 min nearly 100 % of the time . All TTA sub-process times also improved . Moreover , achieving TTA < 60 min significantly reduced the need for ICU consultation or admission ( P = 0.003 ) in this population . Conclusion Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes . These data indicate that decreasing TTA to < 60 min is achievable and associated with improved outcomes in pediatric patients with cancer and Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Children with cancer and fever are at high risk for sepsis related death .  Rapid antibiotic delivery ( < 60 minutes ) has been shown to reduce mortality . We compared patient outcomes and describe interventions from three separate quality improvement ( QI ) projects conducted in three United States ( US ) tertiary care pediatric emergency departments ( EDs ) with the shared aim to reduce time to antibiotic ( TTA ) to < 60 minutes in febrile pediatric oncology patients ( Temperature > 38.0 C ) . A secondary objective was to identify interventions amenable to translation to other centers . We conducted a post project analysis of prospect ively collected observational data from children < 18 years visiting these EDs during independently conducted QI projects .  Comparisons were made pre to post intervention periods within each institution . All interventions were derived independently using QI methods by each institution . Successful as well as unsuccessful interventions were described and common interventions adopted by all sites identified . A total of 1032 ED patient visits were identified from the three projects . Improvement in median TTA delivery ( min ) pre to post intervention(s ) was 118.5–57.0 at site 1 , 163.0–97.5 at site 2 , and 188.0–111.5 at site 3 ( p<.001 all sites ) . The eight common interventions were 1 ) Triage application of topical anesthetic 2 ) Rapid room placement & triage 3 ) Resuscitation room placement of ill appearing children 4 ) Close proximity to central line equipment 5 ) Antibiotic administration before laboratory analyses 6 ) Consensus clinical practice guideline establishment 7 ) Family pre-ED education for fever and 8) Staff project up date s. This core set of eight low cost , high yield QI interventions were developed independently by the three ED 's which led to substantial reduction in time to antibiotic delivery in children with cancer presenting with fever . These interventions may inform future QI initiatives in other setting s caring for febrile pediatric oncology patients PURPOSE Febrile neutropenia ( FN ) is an oncologic emergency , and prolonged time to antibiotic administration ( TTA ) is associated with increased hospital length of stay ( LOS ) and worse outcomes . We hypothesized that a febrile neutropenia pathway ( FNP ) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department ( ED ) . METHODS This prospect i ve study compared ED FNP patients ( > 18 years old ) , between June 2012 and June 2013 with both historical and direct admissions ( DA ) cohorts at a multispecialty academic center . Interventions included providing patients with FN-Alert cards , st and ardizing the definition of FN and recognizing it as a distinct chief complaint , revising ED triage level for FN , creating electronic FN order sets , administering empiric antibiotics before neutrophil count result , and relocating FN antibiotics to the ED . The primary outcome was TTA , with a target goal of 90 minutes after ED presentation . RESULTS In total , 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts , respectively . Use of the FNP  reduced TTA from 235 and 169 minutes in historical and DA cohorts , respectively , to 81 minutes , and from 96 to 68 minutes when the order set was not used versus used in the FNP group ( P < .001 for all comparisons ) . Decrease in hospital LOS was not statistically significant . CONCLUSION The ED FNP is a significant quality initiative with sustainable interventions , and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED BACKGROUND Time-to-antibiotic ( TTA ) administration is a widely used quality -of-care measure for children with cancer and febrile neutropenia ( FN ) . We sought to determine whether TTA is associated with outcomes of FN . PROCEDURE A single-center , retrospective cohort study was conducted of 1,628 FN admissions from 653 patients from 2001 to 2009 . Outcome variables included ( 1 ) an adverse event ( AE ) composite of in-hospital mortality , pediatric intensive care unit ( PICU ) admission within 24 hours of presentation , and /or fluid resuscitation ≥ 40 ml/kg within 24 hours of presentation and ( 2 ) length of stay ( LOS ) . TTA was measured as a continuous variable and in 60-minute intervals . Mixed regression models were constructed to evaluate associations of TTA with the outcome variables after adjusting for relevant covariates including cancer diagnosis , degree of myelosuppression , and presence of bacteremia . RESULTS The composite AE outcome occurred in 11.1 % of admissions including 0.7 % in-hospital mortality , 4.7 % PICU admission , and 10.1 % fluid resuscitation . In univariate analysis , TTA was associated with the composite AE outcome ( Odds Ratio [ OR ] 1.29 , 95 % CI 1.02 - 1.64 ) but not LOS . In multivariate analysis , after adjustment for relevant covariates , 60-minute TTA intervals were associated with the composite AE outcome ( 61 - 120 minutes vs. ≤ 60 minutes , OR 1.81 , 95 % CI 1.01 - 3.26 ) . Unexpectedly , admission from the emergency department ( ED ) was also independently associated with the composite AE outcome ( ED vs. clinic , OR 3.15 , 95 % CI 1.95 - 5.09 ) . CONCLUSIONS TTA and presentation to the ED are independently associated with poor outcomes of FN Objectives Patients with febrile neutropenia are at high risk of morbidity and mortality from infectious causes . Decreasing time to antibiotic ( TTA ) administration is associated with improved patient outcomes . We sought to reduce TTA for children presenting to the emergency department with fever and neutropenia . Methods In a prospect i ve cohort study with historical comparison , TTA administration was evaluated in patients with neutropenia presenting to the Children 's of Alabama Emergency Department . A protocol was established to reduce delays in antibiotic administration and increase the percentage of patients who receive treatment within 60 minutes of presentation . One hundred pre- protocol patient visits between August 2010 and December 2011 were evaluated and 153 post- protocol visits were evaluated between August 2012 and September 2013 . We review ed individual cases to determine barriers to rapid antibiotic administration . Results Antibiotics were administered in 96.9 ± 57.8 minutes in the pre- protocol patient group , and only 35 % of patients received antibiotics within 60 minutes of presentation and 70 % received antibiotics within 120 minutes . After implementation of the protocol , TTA for neutropenic patients was decreased to 64.3 ± 28.4 minutes ( P < 0.0001 ) with 51.4 % receiving antibiotics within 60 minutes and 93.2 % within 120 minutes . Conclusions Implementing a st and ard approach to patients at risk for neutropenia decreased TTA . There are numerous challenges in providing timely antibiotics to children with febrile neutropenia . Identified delays included venous access ( time to effect of topical anesthetics , and difficulty obtaining access ) , physicians waiting on laboratory results , and antibiotic availability BACKGROUND Fever and chemotherapy-induced neutropenia ( FN ) is the most frequent potentially lethal complication of therapy in children with cancer . This study aim ed to describe serious medical complications ( SMC ) in children with FN regarding incidence , clinical spectrum , and associated characteristics . PROCEDURE Pediatric patients presenting with FN induced by non-myeloablative chemotherapy were observed in a prospect i ve multicenter study . SMC was defined as potentially life-threatening complication ( PLTC ) , transfer to the pediatric intensive care unit ( PICU ) , or death . RESULTS A total of 443 FN episodes were reported from 8 centers . 
    Output:
    
This review supports the assertion that TTA can be considered a measure of quality of care , emphasizes the importance of education and training , and describes the very different interventions which have effectively reduced TTA