***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 The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer . Patients with hematologic malignancy ( leukemia or stage III/IV non-Hodgkin lymphoma ) who presented with fever and neutropenia ( ANC < 500/mm3 ) and patients with solid tumors who presented with fever and severe neutropenia ( ANC < 100/mm3 ) were considered to be at high risk and eligible for this study . In this prospect i ve study , 33 patients with 50 febrile neutropenic episodes received iv meropenem ( 20 mg/kg every 8 h ) plus amikacin ( 15 mg/kg/d in 2 divided doses ) ( in 31 episodes ) or piperacillin/tazobactam ( 100 mg/4 mg/kg every 8 h ) plus netilmicin ( 7 mg/kg every 24 h ) ( in 19 episodes ) . Clinical response was determined at 72 h and at completion of the therapy . The groups were comparable in terms of age , sex , initial ANC , use of growth factors , and classification of the infections . An infection was documented microbiologically in 12 episodes ( 39 % ) in the meropenem plus amikacin group and in 8 episodes ( 42 % ) in the piperacillin/tazobactam plus netilmicin group . Of the 22 microbiological isolates , 37 % were gram-positives , 45 % were gram-negatives , and 18 % were fungi . Most of the clinical ly documented infections were of lower respiratory tract , gastrointestinal mucosa , or urinary tract origin . The mean duration of neutropenia was 9 days in both groups . Fever persisted for 1–30 days ( mean 3 vs. 5 days ) . The success rate with initial empiric therapy was 52 % in the meropenem plus amikacin and 42 % in the piperacillin/tazobactam plus netilmicin group , respectively ( p= .5 ) . Total success rate ( with or without modification ) was 97 % vs. 90 % in the episodes . Three patients died due to infection ( 1 vs. 2 patients ) . No major adverse effects were observed in each group . Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients A prospect i ve , r and omized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia . Patients aged 2–16 years with hematological malignancies who had febrile neutropenia were r and omly assigned to receive piperacillin/tazobactam ( 80 mg/kg piperacillin/10 mg/kg tazobactam , q6h ) combined with amikacin ( PTA ) ( 7.5 mg/kg , q12h ) or meropenem or imipenem ( 20 mg/kg , q8h ) ( C ) . Response to antimicrobial therapy , evaluated for etiological agents , was measured . Duration of fever , neutropenia , and hospitalization , mortality , and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups . Out of 87 febrile neutropenic episodes that were evaluable for comparison , 46 patients received PTA and 41 patients were treated with carbapenems ( imipenem or meropenem ) . Overall , the microbiologically documented infection rate was 21.9 % , with Staphylococcus epidermidis as the most common cause of bacteremia . The rate of treatment modification was 56.5 % in the PTA group and 53.6 % in the carbapenem group with no statistical difference ( p > . 05 ) . There was no infection-related mortality during the study period . There was no difference between the two regimens for duration s of fever , neutropenia , and hospitalization ( p > . 05 for all categories ) . PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies Meropenem is a promising carbapenem antibiotic as an empirical monotherapy in patients with febrile neutropenia ( FN ) . With the limited data of the therapy in pediatric patients , the authors conducted this study to evaluate the efficacy and safety of meropenem as empirical antibiotic therapy in 30 pediatric cancer patients with FN ( mean age = 7.5 years ) , who were admitted to King Chulalongkorn Memorial Hospital from May 2000 to December 2001 .  Meropenem 60 mg/kg/day was given intravenously every 8 hours . The efficacy of meropenem was assessed as successful , inconclusive and failure on days 3 and 5 of the therapy and compared to that of 
    Output:
    
Conclusions Our meta- analysis suggests that APP – aminoglycoside , APP monotherapy , and carbapenem monotherapy are all efficacious therapeutic options for the empiric management of pediatric FN