***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: Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Recent reports and previous r and omized trials conducted at the authors ' institution suggested that children with lower risk febrile neutropenic ( LRFN ) may benefit from substitution of oral antibiotic therapy for parenteral therapy . The objective of this study was to determine the efficacy of parenteral‐oral outpatient therapy in the management of children with LRFN who were receiving treatment for malignant disease Affordability of costly in-patient medical care and accessibility to the few cancer centres are serious problems faced by cancer patients in developing countries . Febrile neutropenia in particular is a major problem because delay in institution of antibiotic therapy can be rapidly fatal . We conducted a prospect i ve non-r and omised trial to evaluate the efficacy of administration of oral ofloxacin by caregivers to paediatric cancer patients with fever and neutropenia . Patients receiving chemotherapy who resided for away and were unable to reach the oncology ward within 12 hours of onset of fever or were unable to afford the expensive in-patient care were eligible for inclusion in the study . Requirements for enrollment included an absolute neutrophil count of < or = 0.5 x 10(9)/L , a temperature of > or = 38 degrees C , and ability to take oral medications . Caregivers were instructed to immediately administer oral ofloxacin on recognition of fever and to maintain constant contact with the oncology staff . Eighty-five of the 91 episodes were evaluable . These were most patients with solid tumours or non-Hodgkin 's lymphoma ( 79 % ) . Duration of neutropenia and fever was short and majority had pyrexia of undetermined origin ( 84 % ) . Seventy-seven ( 91 % ) of the febrile episodes responded to ofloxacin with resolution of fever and neutropenia and hospitalisation was never required . Eight ( 9 % ) patients required hospitalisation . Most of them had prolonged neutropenia . They all responded to parenteral antibiotic therapy . No toxicity was observed and the cost of therapy was negligible . Out-patient therapy with oral ofloxacin may be an alternative to hospitalisation for those paediatric patients who are unable to afford or do not have access to in-patient care Fever and neutropenia ( F&N ) is a common complication of cancer chemotherapy . It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics . This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as out patients OBJECTIVE To compare the use of intravenous vs. oral antibiotic therapy . METHODS All febrile neutropenic patients younger than 18 years old with low risk of complications and receiving chemotherapy were selected . The study was conducted from 2002 to 2005 at the Pediatric Oncology Unit of Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil . Patients were divided into group A and group B and were r and omly assigned to receive oral or intravenous therapy . The empirical antimicrobial treatment used for group A consisted in oral ciprofloxacin plus amoxicillin-clavulanate and intravenous placebo , and group B received cefepime and oral placebo . RESULTS A total of 91 consecutive episodes of febrile neutropenia in 58 children were included in the study . For patients of group A , treatment failure rate was 51.2 % ; the mean length of hospital stay was 8 days ( range 2 - 10 days ) . For patients treated with intravenous antibiotic therapy , treatment failure rate was 45.8 % ; the mean length of hospital stay was 7 days ( range 3 - 10 days ) . CONCLUSION There was no difference in the outcome in oral vs. intravenous therapy . There is need of larger r and omized trials before oral empirical therapy administered to this population should be considered the new st and ard of treatment Background : Fluoroquinolones , including levofloxacin , have not been recommended for use in children largely because studies in juvenile laboratory animals suggest there may be an increased risk of fluoroquinolone-associated cartilage lesions . A large prospect i ve trial is needed to assess the risks associated with using levofloxacin in children . Objective : Assess the safety and tolerability of levofloxacin therapy in children based on observations for 1 year after therapy . Methods : Safety data were collected in children who participated in 1 of 3 efficacy trials ( N = 2523 ) and a subset of these children who also subsequently participated in a long-term 1-year surveillance trial ( N = 2233 ) . Incidence of adverse events in children r and omized to receive levofloxacin versus nonfluoroquinolone antibiotics  was compared . Based on assessment s by treating physicians and an independent data safety monitoring committee , events related to the musculoskeletal system were further categorized as 1 of 4 predefined musculoskeletal disorders ( arthralgia , arthritis , tendinopathy , gait abnormality ) considered most likely clinical correlates of fluoroquinolone-associated cartilage lesions observed in laboratory animals . Results : Levofloxacin was well tolerated during and for 1 month after therapy as evidence d by similar incidence and character of adverse events compared with nonfluoro 
    Output:
    
Experience with fluoroquinolones demonstrates excellent outcomes and short-term safety , although reported studies have been restricted to low-risk patients .
Fluoroquinolones can be comfortably adopted for low-risk FN , although experience in high-risk FN is uncertain in pediatrics