***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: 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 Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries . Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock , and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia . We analyzed factors associated with ( 1 ) Longer times from fever onset to hospital presentation/antibiotic treatment and ( 2 ) Sepsis and infection-related mortality . Method This prospect i ve cohort study included children aged 0–16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital , San Salvador . We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode . Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented . Findings Of 251 children enrolled , 215 had acute lymphoblastic leukemia ( 85.7 % ) . Among 269 outpatient febrile episodes , median times from fever to deciding to seek medical care was 10.0 hours ( interquartile range [ IQR ] 5.0–20.0 ) , and from decision to seek care to first hospital visit was 1.8 hours ( IQR 1.0–3.0 ) . Forty-seven ( 17.5 % ) patients developed sepsis and 7 ( 2.6 % ) died of infection . Maternal illiteracy was associated with longer time from fever to decision to seek care ( P = 0.029 ) and sepsis ( odds ratio [ OR ] 3.06 , 95 % confidence interval [ CI ] 1.09–8.63 ; P = 0.034 ) . More infectious deaths occurred in those with longer travel time to hospital ( OR 1.36 , 95 % CI 1.03–1.81 ; P = 0.031 ) and in families with an annual household income < US$ 2,000 ( OR 13.90 , 95 % CI 1.62–119.10 ; P = 0.016 ) . Interpretation Illiteracy , poverty , and longer travel times are associated with delays in assessment and treatment of fever and with sepsis and infectious mortality in pediatric leukemia . Providing additional education to high-risk families and staying at a nearby guest house during periods of neutropenia may decrease sepsis and infectious mortality 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 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 Background Fever and  neutropenia ( FN ) is a common complication of chemotherapy for cancer . Prompt empiric broad-spectrum antibiotic therapy in FN is typically considered st and ard of care , but the definition of prompt is not clear . We seek to systematic ally review the available data on the association between time to antibiotics ( TTA ) administration and clinical outcomes in patients with FN being treated with chemotherapy .  There have been several efforts to reduce TTA in patients with FN , by implementing specific interventions , presuming there will be a beneficial effect on patient-important outcomes . This systematic review will also collect data on such interventions and their effect to reduce TTA and potentially change clinical outcomes . Methods / design The search will cover MEDLINE , MEDLINE In-Process & Other Non-Indexed Citations , EMBASE , CINAHL , CDSR , CENTRAL , and LILACS . A full- search strategy is provided . Lists of studies identified by references cited and forward citation search ing of included articles will also be review ed . Studies will be screened , and data extracted by one research er and independently checked by a second . Confounding biases and quality of studies will be assessed with the risk of bias in non-r and omised studies -of interventions ( ROBINS-I ) tool . Data will be presented in narrative and tabular forms ; in addition , if appropriate data is available , r and om effects meta- analysis will be used to examine TTA.A detailed analysis plan , including an assessment of heterogeneity and publication bias , is provided . Discussion This study aims to evaluate the association between TTA and patient-important clinical outcomes . Additionally , it will identify , critically appraise , and synthesis e information on performed interventions and its effect to reduce TTA as a way of gaining insight into the potential use of these approaches . This will provide better knowledge for an adjusted treatment approach of FN . Systematic review registration PROSPERO [ CRD42018092948 
    Output:
    
There seems to be an association between longer TTA and impaired safety .