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    Input: Additional unpublished data are presented from a study by Cotton and Evans in 1990 on the use of Irlen ( tinted ) lenses as an intervention for 22 children with a reading disability . These data reinforce rhe earlier conclusion that the r and om facilitatory effects of the lenses are very likely attributional and motivational in nature Background It is possible that cross-over studies included in current systematic review s are being inadequately assessed , because the current risk of bias tools do not consider possible biases specific to cross-over design . We performed this study to evaluate whether this was being done in  cross-over studies included in Cochrane  Systematic Review s ( CSRs ) . Methods We search ed the Cochrane Library ( up to 2013 issue 5 ) for CSRs that included at least one cross-over trial . Two authors independently undertook the study selection and data extraction . A r and om sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane h and book . In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane h and book . Results We identified 688 CSRs that included one or more cross-over studies . We chose a r and om sample of 60 CSRs and these included 139 cross-over studies . None of these CSRs undertook a risk of bias assessment specific for cross-over studies . In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs . When we reassessed the risk of bias , including the 3 items specific to cross-over trials , of these 139 studies , a low risk of bias was judged for appropriate cross-over design in 110(79 % ) , carry-over effects in 48(34 % ) and for reporting data in all stages of the trial in 114(82 % ) . Assessment of biases in cross-over trials could affect the GRADE assessment of a review ’s findings . Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies . Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs . A proposed check list for the evaluation of cross-over trials is provided Background We explore whether the number of null results in large National Heart Lung , and Blood Institute ( NHLBI ) funded trials has increased over time . Methods We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease . Trials were included if direct costs > $ 500,000/year , participants were adult humans , and the primary outcome was cardiovascular risk , disease or death .  The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000 , whether they registered in clinical trials.gov prior to publication , used active or placebo comparator , and whether or not the trial had industry co-sponsorship . We tabulated whether the study reported a positive , negative , or null result on the primary outcome variable and for total mortality . Results 17 of 30 studies ( 57 % ) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 ( 8 % ) trials published after 2000 ( χ2=12.2,df= 1 , p=0.0005 ) . There has been no change in the proportion of trials that compared treatment to placebo versus active comparator . Industry co-sponsorship was unrelated to the probability of reporting a significant benefit . Pre- registration in clinical trials.gov was strongly associated with the trend toward null findings . Conclusions The number NHLBI trials reporting positive results declined after the year 2000 . Prospect i ve declaration of outcomes in RCTs , and the adoption of transparent reporting st and ards , as required by clinical trials.gov , may have contributed to the trend toward null findings Aim : To test a theory of visual stress by investigating the inter-relationships between ( 1 ) the threshold contrast/saturation at which individuals first report discomfort when viewing colored gratings of progressively increasing contrast and decreasing saturation ; ( 2 ) the choice of a colored overlay for reading ; ( 3 ) any increase in reading speed when the overlay is used . Method : Ninety-five young adults , with normal color vision , reported illusions from square-wave gratings ( Pattern Glare Test ) , chose any colored overlays that improved clarity ( Intuitive Color Overlays ) and read aloud r and omly ordered common words ( Wilkins Rate of Reading Test ) . This was followed by an automated choice of tints for text using various screen colors on a tablet , and a test of discomfort from patterns of progressively increasing contrast and decreasing saturation , using software developed for this study . All participants wore their optimal refractive correction throughout the procedure . Results : Fifty-eight participants chose a colored overlay and reported that it made text easier and more comfortable to read . On average , these individuals had a greater improvement in reading speed with their overlays ( p = 0.003 ) , a lower contrast threshold at which discomfort from achromatic gratings was first reported ( p = 0.015 ) , and a tendency to report more pattern glare ( p = 0.052 ) , compared to the other participants . Participants who chose both a most and least preferred tint for text using the automated procedure reported discomfort from colored gratings at a significantly higher contrast with their most preferred color compared to their least preferred color ( p = 0.003 ) . The choice of a colored tint was moderately consistent across tests . The most and least preferred colors tended to be complementary . Conclusion : Colored tints that improved reading speed reduced pattern glare both in terms of the illusion susceptibility and in terms of discomfort contrast threshold , supporting a theory of visual stress . An automated test that incorporates colored gratings and a choice of most and least preferred color might better identify individuals whose reading speed improves with colored overlays Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Purpose : Visual disturbances that make it difficult to read text are often termed “ visual stress ” . Coloured filters in spectacles may help some children overcome reading problems that are often caused by visual stress . It has been suggested that for optimal effect each child requires an individually prescribed colour for each eye , as determined in systems such as the “ Harris Foundation ” coloured filters . Alternatively , it has been argued that only blue or yellow filters , as used in the “ Dyslexia Research Trust ” ( DRT ) filter system , are necessary to affect the underlying physiology . Method : A r and omised , double blind trial with 73 delayed readers , was undertaken to compare changes in reading and spelling as well as irregular and non-word reading skills after 3 months of wearing either the Harris or the DRT filters . Results : Reading improved significantly after wearing either type of filter ( t = −8.4 , p < 0.01 ) , with 40 % of the children improving their reading age by 6 months or more during the 3 month trial . However , spelling ability ( t = 2.1 , p = 0.05 ) and non-word reading ( f = 4.7 , p < 0.05 ) improved significantly more with the DRT than with the Harris filters . Conclusion : Education and rehabilitation professionals should therefore , consider coloured filters as an effective intervention for delayed readers experiencing visual stress . Implication s for Rehabilitation Any disability that impacts on a child ’s capacity to read has serious implication s for academic development as well as the ability to participate independently in activities of daily living . One reading disability , generally termed “ visual stress ” , is related to visual disturbances that make it difficult to read text . This research demonstrates the beneficial use of coloured filters for promoting visual reading capacity for children with visual stress . Professionals who are involved in the needs of children with reading delay , may like to consider the benefits that coloured filters can afford children with visual reading problems PURPOSE To investigate the impact of colored overlays on the accommodative response of individuals , with and without pattern-related visual stress ( PRVS ) , a condition in which individuals manifest symptoms of perceptual distortion and discomfort when viewing a 3-cyc/deg square-wave grating . METHODS Under double-masked conditions , 11 individuals who reported PRVS selected an overlay with a color individually chosen to reduce perceptual distortion of text and maximize comfort ( PRVS group ) . Two groups of control subjects individually matched for age , sex , and refractive error were recruited . Control group 1 similarly chose an overlay to maximize comfort . Control group 2 used the same overlays as the paired PRVS participant . The overlay improved reading speed by 10 % ( P < 0.001 ) , but only in the PRVS group . A remote eccentric photorefractor was used to record accommodative lag while participants viewed a cross on a background . The background was uniform or contained a grating and was either gray or had a chromaticity identical with that of the chosen overlay . There were therefore four background s in all . RESULTS Overall , the accommodative lag was 0.44 D greater in the participants with PRVS . When the background had the chosen chromaticity , the accommodative lag was reduced by an average of 0.16 D ( P = 0.03 ) in the PRVS group , but not in the symptom-free groups : in control group 2 the colored background slightly increased the accommodative lag . CONCLUSIONS Accommodative lag was greater in individuals susceptible to pattern-related visual stress and was reduced by a colored background Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT Some individuals read more fluently when the text is coloured : i.e. , when coloured sheets of plastic ( overlays ) are placed upon the page , or when coloured lenses are worn . Overlays provide a surface colour whereas lenses mimic a change in the colour of a light source . The neural mechanisms that underlie colour constancy ensure that the chromaticity of overlays and lenses is processed differently by the visual system . We investigated ( 1 ) the relationship between the optimal colours of overlays and lenses , and ( 2 ) how reading rate is affected by a particular colour in overlays and lenses .  In 100 patients we noted ( 1 ) the overlay(s ) chosen from among the 29 combinations of the 10 IOO Intuitive Overlays which sample chromaticity systematic ally and ( 2 ) the chromaticity co-ordinates of the lenses subsequently chosen using the intuitive Colorimeter , a device providing a light source that can be adjusted in hue , saturation and luminance independently . The relationship between the chromaticities of the overlays and the lenses showed considerable variation . In a second study , patients attending the Specific Learning Difficulties clinic at the Institute of Optometry , London , were given overlays to use for two months . Seventeen who derived benefit were examined using the  Intuitive Colorimeter .  Patients were asked to read aloud r and omly ordered common words ( Wilkins Rate of Reading Test ) : ( 1 ) with no colour , ( 2 ) with the chosen overlay , ( 3 ) with lenses matching the chosen overlay and ( 4 ) with lenses matching the Colorimeter setting . The aids increased reading rate significantly only in conditions ( 2 ) and ( 4 ) . There was no significant improvement when lenses matching the overlay colour were used , and under this condition the reading rate was significantly poorer than in conditions ( 2 ) and ( 4 ) . The colour of a lens will improve reading only if it is selected under conditions that mimic a change in the colour of a light source : coloured overlays give no clinical ly reliable guide to optimal lens colour A simple reading test that can be undertaken by disabled readers is described . The test is suitable for use in the optometric clinic , taking less than 2 minutes to administer per passage . Test-retest scores are acceptably reliable . The test reveals increases in the speed of reading when coloured overlays are used both ( 1 ) in children who have made long-term use of coloured overlays for reading , and ( 2 ) in children who will subsequently do so Ninety-three children in a primary school and 59 children in two first-year classes of a secondary school were asked individually to observe a paragraph of r and om letters arranged to resemble 
    Output:
    
agent
While many studies report improvements with coloured lenses , the effect size is generally small and /or similar to the improvement found with a placebo condition .
Consistent with previous review s and advice from several professional bodies , we conclude that the use of coloured lenses or overlays to ameliorate reading difficulties can not be endorsed and that any benefits reported by individuals in clinical setting s are likely to be the result of placebo , practice or Hawthorne effects
***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: Additional unpublished data are presented from a study by Cotton and Evans in 1990 on the use of Irlen ( tinted ) lenses as an intervention for 22 children with a reading disability . These data reinforce rhe earlier conclusion that the r and om facilitatory effects of the lenses are very likely attributional and motivational in nature Background It is possible that cross-over studies included in current systematic review s are being inadequately assessed , because the current risk of bias tools do not consider possible biases specific to cross-over design . We performed this study to evaluate whether this was being done in  cross-over studies included in Cochrane  Systematic Review s ( CSRs ) . Methods We search ed the Cochrane Library ( up to 2013 issue 5 ) for CSRs that included at least one cross-over trial . Two authors independently undertook the study selection and data extraction . A r and om sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane h and book . In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane h and book . Results We identified 688 CSRs that included one or more cross-over studies . We chose a r and om sample of 60 CSRs and these included 139 cross-over studies . None of these CSRs undertook a risk of bias assessment specific for cross-over studies . In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs . When we reassessed the risk of bias , including the 3 items specific to cross-over trials , of these 139 studies , a low risk of bias was judged for appropriate cross-over design in 110(79 % ) , carry-over effects in 48(34 % ) and for reporting data in all stages of the trial in 114(82 % ) . Assessment of biases in cross-over trials could affect the GRADE assessment of a review ’s findings . Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies . Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs . A proposed check list for the evaluation of cross-over trials is provided Background We explore whether the number of null results in large National Heart Lung , and Blood Institute ( NHLBI ) funded trials has increased over time . Methods We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease . Trials were included if direct costs > $ 500,000/year , participants were adult humans , and the primary outcome was cardiovascular risk , disease or death .  The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000 , whether they registered in clinical trials.gov prior to publication , used active or placebo comparator , and whether or not the trial had industry co-sponsorship . We tabulated whether the study reported a positive , negative , or null result on the primary outcome variable and for total mortality . Results 17 of 30 studies ( 57 % ) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 ( 8 % ) trials published after 2000 ( χ2=12.2,df= 1 , p=0.0005 ) . There has been no change in the proportion of trials that compared treatment to placebo versus active comparator . Industry co-sponsorship was unrelated to the probability of reporting a significant benefit . Pre- registration in clinical trials.gov was strongly associated with the trend toward null findings . Conclusions The number NHLBI trials reporting positive results declined after the year 2000 . Prospect i ve declaration of outcomes in RCTs , and the adoption of transparent reporting st and ards , as required by clinical trials.gov , may have contributed to the trend toward null findings Aim : To test a theory of visual stress by investigating the inter-relationships between ( 1 ) the threshold contrast/saturation at which individuals first report discomfort when viewing colored gratings of progressively increasing contrast and decreasing saturation ; ( 2 ) the choice of a colored overlay for reading ; ( 3 ) any increase in reading speed when the overlay is used . Method : Ninety-five young adults , with normal color vision , reported illusions from square-wave gratings ( Pattern Glare Test ) , chose any colored overlays that improved clarity ( Intuitive Color Overlays ) and read aloud r and omly ordered common words ( Wilkins Rate of Reading Test ) . This was followed by an automated choice of tints for text using various screen colors on a tablet , and a test of discomfort from patterns of progressively increasing contrast and decreasing saturation , using software developed for this study . All participants wore their optimal refractive correction throughout the procedure . Results : Fifty-eight participants chose a colored overlay and reported that it made text easier and more comfortable to read . On average , these individuals had a greater improvement in reading speed with their overlays ( p = 0.003 ) , a lower contrast threshold at which discomfort from achromatic gratings was first reported ( p = 0.015 ) , and a tendency to report more pattern glare ( p = 0.052 ) , compared to the other participants . Participants who chose both a most and least preferred tint for text using the automated procedure reported discomfort from colored gratings at a significantly higher contrast with their most preferred color compared to their least preferred color ( p = 0.003 ) . The choice of a colored tint was moderately consistent across tests . The most and least preferred colors tended to be complementary . Conclusion : Colored tints that improved reading speed reduced pattern glare both in terms of the illusion susceptibility and in terms of discomfort contrast threshold , supporting a theory of visual stress . An automated test that incorporates colored gratings and a choice of most and least preferred color might better identify individuals whose reading speed improves with colored overlays Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Purpose : Visual disturbances that make it difficult to read text are often termed “ visual stress ” . Coloured filters in spectacles may help some children overcome reading problems that are often caused by visual stress . It has been suggested that for optimal effect each child requires an individually prescribed colour for each eye , as determined in systems such as the “ Harris Foundation ” coloured filters . Alternatively , it has been argued that only blue or yellow filters , as used in the “ Dyslexia Research Trust ” ( DRT ) filter system , are necessary to affect the underlying physiology . Method : A r and omised , double blind trial with 73 delayed readers , was undertaken to compare changes in reading and spelling as well as irregular and non-word reading skills after 3 months of wearing either the Harris or the DRT filters . Results : Reading improved significantly after wearing either type of filter ( t = −8.4 , p < 0.01 ) , with 40 % of the children improving their reading age by 6 months or more during the 3 month trial . However , spelling ability ( t = 2.1 , p = 0.05 ) and non-word reading ( f = 4.7 , p < 0.05 ) improved significantly more with the DRT than with the Harris filters . Conclusion : Education and rehabilitation professionals should therefore , consider coloured filters as an effective intervention for delayed readers experiencing visual stress . Implication s for Rehabilitation Any disability that impacts on a child ’s capacity to read has serious implication s for academic development as well as the ability to participate independently in activities of daily living . One reading disability , generally termed “ visual stress ” , is related to visual disturbances that make it difficult to read text . This research demonstrates the beneficial use of coloured filters for promoting visual reading capacity for children with visual stress . Professionals who are involved in the needs of children with reading delay , may like to consider the benefits that coloured filters can afford children with visual reading problems PURPOSE To investigate the impact of colored overlays on the accommodative response of individuals , with and without pattern-related visual stress ( PRVS ) , a condition in which individuals manifest symptoms of perceptual distortion and discomfort when viewing a 3-cyc/deg square-wave grating . METHODS Under double-masked conditions , 11 individuals who reported PRVS selected an overlay with a color individually chosen to reduce perceptual distortion of text and maximize comfort ( PRVS group ) . Two groups of control subjects individually matched for age , sex , and refractive error were recruited . Control group 1 similarly chose an overlay to maximize comfort . Control group 2 used the same overlays as the paired PRVS participant . The overlay improved reading speed by 10 % ( P < 0.001 ) , but only in the PRVS group . A remote eccentric photorefractor was used to record accommodative lag while participants viewed a cross on a background . The background was uniform or contained a grating and was either gray or had a chromaticity identical with that of the chosen overlay . There were therefore four background s in all . RESULTS Overall , the accommodative lag was 0.44 D greater in the participants with PRVS . When the background had the chosen chromaticity , the accommodative lag was reduced by an average of 0.16 D ( P = 0.03 ) in the PRVS group , but not in the symptom-free groups : in control group 2 the colored background slightly increased the accommodative lag . CONCLUSIONS Accommodative lag was greater in individuals susceptible to pattern-related visual stress and was reduced by a colored background Background The ' Hawthorne Effect ' may be an important factor affecting the generalisability of clinical research to routine practice , but has been little studied . Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge , no attempt has been made to quantify them . Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia . Methods Participants in a dementia trial were r and omised to intensive follow-up ( with comprehensive assessment visits at baseline and two , four and six months post r and omisation ) or minimal follow-up ( with an abbreviated assessment at baseline and a full assessment at six months ) . Our primary outcomes were cognitive functioning ( ADAS-Cog ) and participant and carer-rated quality of life ( QOL-AD ) . Results We recruited 176 participants , mainly through general practice s. The main analysis was based on Intention to treat ( ITT ) , with available data . In the ANCOVA model with baseline score as a co-variate , follow-up group had a significant effect on outcome at six months on the ADAS-Cog score ( n = 140 ; mean difference = -2.018 ; 95%CI -3.914 , -0.121 ; p = 0.037 favouring the intensive follow-up group ) , and on participant-rated quality of life score ( n = 142 ; mean difference = -1.382 ; 95%CI -2.642 , -0.122 ; p = 0.032 favouring minimal follow-up group ) . There was no significant difference on carer quality of life . Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia result ed in a better outcome than minimal follow-up , as measured by their cognitive functioning . Trial registration Current controlled trials : IS RCT Some individuals read more fluently when the text is coloured : i.e. , when coloured sheets of plastic ( overlays ) are placed upon the page , or when coloured lenses are worn . Overlays provide a surface colour whereas lenses mimic a change in the colour of a light source . The neural mechanisms that underlie colour constancy ensure that the chromaticity of overlays and lenses is processed differently by the visual system . We investigated ( 1 ) the relationship between the optimal colours of overlays and lenses , and ( 2 ) how reading rate is affected by a particular colour in overlays and lenses .  In 100 patients we noted ( 1 ) the overlay(s ) chosen from among the 29 combinations of the 10 IOO Intuitive Overlays which sample chromaticity systematic ally and ( 2 ) the chromaticity co-ordinates of the lenses subsequently chosen using the intuitive Colorimeter , a device providing a light source that can be adjusted in hue , saturation and luminance independently . The relationship between the chromaticities of the overlays and the lenses showed considerable variation . In a second study , patients attending the Specific Learning Difficulties clinic at the Institute of Optometry , London , were given overlays to use for two months . Seventeen who derived benefit were examined using the  Intuitive Colorimeter .  Patients were asked to read aloud r and omly ordered common words ( Wilkins Rate of Reading Test ) : ( 1 ) with no colour , ( 2 ) with the chosen overlay , ( 3 ) with lenses matching the chosen overlay and ( 4 ) with lenses matching the Colorimeter setting . The aids increased reading rate significantly only in conditions ( 2 ) and ( 4 ) . There was no significant improvement when lenses matching the overlay colour were used , and under this condition the reading rate was significantly poorer than in conditions ( 2 ) and ( 4 ) . The colour of a lens will improve reading only if it is selected under conditions that mimic a change in the colour of a light source : coloured overlays give no clinical ly reliable guide to optimal lens colour A simple reading test that can be undertaken by disabled readers is described . The test is suitable for use in the optometric clinic , taking less than 2 minutes to administer per passage . Test-retest scores are acceptably reliable . The test reveals increases in the speed of reading when coloured overlays are used both ( 1 ) in children who have made long-term use of coloured overlays for reading , and ( 2 ) in children who will subsequently do so Ninety-three children in a primary school and 59 children in two first-year classes of a secondary school were asked individually to observe a paragraph of r and om letters arranged to resemble 
    Output:
    