human
***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 Background and Purpose — The purpose of this study was to assess the effects of stroke involvement of primary and secondary hemispheric motor systems and corticofugal tracts on arm and h and recovery . Methods — Forty-one patients participating in an inpatient stroke rehabilitation data base , admitted 17±2 ( SEM ) days after initial unilateral hemispheric ischemic stroke , with neuroimaging studies performed > 48 hours after stroke and with minimal upper limb ( UL ) movement ( admission Fugl-Meyer UL motor scores ≤9 ; normal score , 58 ) were studied . Patients were divided into 3 groups according to their UL discharge Fugl-Meyer score : 0 to 9 , no/poor recovery ; 10 to 18 , well-defined flexion-extension synergies ; and > 18 , synergies+isolated movements . Lesions affecting the following structures were recorded : primary motor cortex , premotor area , supplementary motor area , anterior half of the middle third of corona radiata ( secondary motor efferents ) , posterior half of the middle third of corona radiata ( primary motor efferents ) , genu , anterior and posterior limbs of the internal capsule ( PLIC ) , basal ganglia , and thalamus . & khgr;2 Analysis and ANOVA were used to study the significance of stroke location on UL motor recovery . Results — The effect of involvement of primary , premotor , or supplementary motor areas on motor recovery did not reach statistical significance . Patients with purely cortical stroke were likely to recover UL isolated movement ( 3 of 4 ) compared with purely subcortical ( 1 of 17 ) or mixed cortical-subcortical stroke location ( 2 of 20 ) ( P = 0.009 ) . Of those with cortical , subcortical , or mixed cortical plus subcortical lesions sparing the PLIC , 5 of 13 recovered isolated UL movement ( P = 0.01 ) . Only 1 of 28 patients with involvement of the PLIC plus adjacent corona radiata , basal ganglia , or thalamus recovered isolated UL movement ( P = 0.01 ) . Patients with small lacunar strokes affecting only the PLIC did not have sufficient motor deficits 2 weeks after stroke to meet inclusion criteria . Conclusions — The probability of recovery of isolated UL movement decreases progressively with lesion location as follows : cortex , corona radiata , and PLIC . This is consistent with our current underst and ing of redundant cortical motor representation and convergence of corticofugal motor efferents as they pass through the corona radiata to the PLIC Background and Purpose — Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials ( MEPs ) elicited by focal transcranial magnetic stimulation ( TMS ) were compared in healthy subjects and patients with acute stroke . Methods — Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices . If present , MEPs evoked in muscles ipsilateral to TMS were analyzed for latency , amplitude , shape , and center of gravity ( ie , preferential coil location to elicit them ) . In stroke patients , possible relationships between early ipsilateral responses and functional outcome at 6 months were sought . Results — With relaxed or slightly contracting target muscle , maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous ( FDI ) or biceps of any of 16 normal subjects . In 5 of 8 healthy subjects tested , ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle ( in biceps , 6 of 8 subjects ) during strong ( > 50 % maximum ) contraction of the target muscle . In 15 of 25 stroke patients , ipsilateral MEPs in the unaffected relaxed FDI ( in biceps , 6 of 25 stroke patients ) were evoked by stimulation of premotor areas of the affected hemisphere . Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere . Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infa rcts . Patients harboring these responses had slightly better bimanual dexterity after 6 months . Conclusions — Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins . In the former , they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways , whereas in the latter , early ipsilateral MEPs could originate in hyperexcitable premotor areas Predictors for the degree of clinical recovery after stroke are still poorly defined . In this study we tried to assess the predictive value of clinical data and of lesion size for motor recovery after ischemic stroke . In 52 hemiparetic patients we monitored the course of clinical recovery by a dedicated score of sensorimotor h and function after their first stroke . The course of the lesion size was measured in proton density magnetic resonance images . Three groups of patients were identified . Patients with moderate initial motor deficit recovered almost completely within 9 days ( 17/17 , group 1 ) . From the patients with severe initial motor deficit , about equal numbers recovered ( 16/35 , group 2 ) or remained severely impaired during the entire observation period of more than  
    Output:
    
agent
The most important predictive factors for upper limb recovery following stroke appears to the initial severity of motor impairment or function
***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 Background and Purpose — The purpose of this study was to assess the effects of stroke involvement of primary and secondary hemispheric motor systems and corticofugal tracts on arm and h and recovery . Methods — Forty-one patients participating in an inpatient stroke rehabilitation data base , admitted 17±2 ( SEM ) days after initial unilateral hemispheric ischemic stroke , with neuroimaging studies performed > 48 hours after stroke and with minimal upper limb ( UL ) movement ( admission Fugl-Meyer UL motor scores ≤9 ; normal score , 58 ) were studied . Patients were divided into 3 groups according to their UL discharge Fugl-Meyer score : 0 to 9 , no/poor recovery ; 10 to 18 , well-defined flexion-extension synergies ; and > 18 , synergies+isolated movements . Lesions affecting the following structures were recorded : primary motor cortex , premotor area , supplementary motor area , anterior half of the middle third of corona radiata ( secondary motor efferents ) , posterior half of the middle third of corona radiata ( primary motor efferents ) , genu , anterior and posterior limbs of the internal capsule ( PLIC ) , basal ganglia , and thalamus . & khgr;2 Analysis and ANOVA were used to study the significance of stroke location on UL motor recovery . Results — The effect of involvement of primary , premotor , or supplementary motor areas on motor recovery did not reach statistical significance . Patients with purely cortical stroke were likely to recover UL isolated movement ( 3 of 4 ) compared with purely subcortical ( 1 of 17 ) or mixed cortical-subcortical stroke location ( 2 of 20 ) ( P = 0.009 ) . Of those with cortical , subcortical , or mixed cortical plus subcortical lesions sparing the PLIC , 5 of 13 recovered isolated UL movement ( P = 0.01 ) . Only 1 of 28 patients with involvement of the PLIC plus adjacent corona radiata , basal ganglia , or thalamus recovered isolated UL movement ( P = 0.01 ) . Patients with small lacunar strokes affecting only the PLIC did not have sufficient motor deficits 2 weeks after stroke to meet inclusion criteria . Conclusions — The probability of recovery of isolated UL movement decreases progressively with lesion location as follows : cortex , corona radiata , and PLIC . This is consistent with our current underst and ing of redundant cortical motor representation and convergence of corticofugal motor efferents as they pass through the corona radiata to the PLIC Background and Purpose — Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials ( MEPs ) elicited by focal transcranial magnetic stimulation ( TMS ) were compared in healthy subjects and patients with acute stroke . Methods — Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices . If present , MEPs evoked in muscles ipsilateral to TMS were analyzed for latency , amplitude , shape , and center of gravity ( ie , preferential coil location to elicit them ) . In stroke patients , possible relationships between early ipsilateral responses and functional outcome at 6 months were sought . Results — With relaxed or slightly contracting target muscle , maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous ( FDI ) or biceps of any of 16 normal subjects . In 5 of 8 healthy subjects tested , ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle ( in biceps , 6 of 8 subjects ) during strong ( > 50 % maximum ) contraction of the target muscle . In 15 of 25 stroke patients , ipsilateral MEPs in the unaffected relaxed FDI ( in biceps , 6 of 25 stroke patients ) were evoked by stimulation of premotor areas of the affected hemisphere . Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere . Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infa rcts . Patients harboring these responses had slightly better bimanual dexterity after 6 months . Conclusions — Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins . In the former , they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways , whereas in the latter , early ipsilateral MEPs could originate in hyperexcitable premotor areas Predictors for the degree of clinical recovery after stroke are still poorly defined . In this study we tried to assess the predictive value of clinical data and of lesion size for motor recovery after ischemic stroke . In 52 hemiparetic patients we monitored the course of clinical recovery by a dedicated score of sensorimotor h and function after their first stroke . The course of the lesion size was measured in proton density magnetic resonance images . Three groups of patients were identified . Patients with moderate initial motor deficit recovered almost completely within 9 days ( 17/17 , group 1 ) . From the patients with severe initial motor deficit , about equal numbers recovered ( 16/35 , group 2 ) or remained severely impaired during the entire observation period of more than  
    Output:
    