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: OBJECTIVE The aim of the current study was to determine the validity of the Toronto Clinical Scoring System ( CSS ) in reflecting the presence and severity of  diabetic peripheral sensorimotor polyneuropathy ( DSP )  as determined by myelinated fiber density ( FD ) on sural nerve biopsy . RESEARCH DESIGN AND METHODS Eighty-nine patients with both type 1 and type 2 diabetes , ascertained from a large therapeutic r and omized controlled trial , were included in this cross-sectional , observational cohort study . Morphological severity of DSP was expressed as the FD in the sural nerve biopsy . The Toronto CSS was applied to all patients to determine a clinical neuropathy score . General linear regression models were used to assess the relationship between the morphological severity of DSP and the Toronto CSS .  RESULTS The Toronto CSS showed a significant negative correlation with sural nerve FD ( R(2 ) = 0.256 , P < 0.0001 ) . The Toronto CSS was lower in those with better glycemic control ( HbA(1c ) < /=8 % ) . Sural nerve FD and the Toronto CSS showed strong correlations with electrophysiology , by both summed amplitude and summed conduction velocity values . CONCLUSIONS The Toronto CSS is a valid instrument to reflect the presence and severity of DSP as measured by sural nerve morphology and electrophysiology . The results of the current study underscore the interrelationships between clinical deficits , electrophysiological findings , and morphological changes in DSP . This evidence suggests that the Toronto CSS may prove useful in documenting and monitoring DSP in the clinic and in clinical research trials The  Patient Evaluation Measure ( PEM ) , The  Michigan H and Outcome Question naire ( MHQ )  and the Disabilities of the Arm , Shoulder and H and ( DASH ) score were assessed independent of their originators for reliability , construct and criterion validity and acceptability , using an ease of use question naire . These were administered in r and om order to 100 patients with different h and and wrist disorders and with different impairments of movement , pain , sensation and strength . The internal consistency of all three question naires was very high suggesting redundancy in the questions . All question naires were reproducible and valid for finger and wrist disorders , but less for nerve disorders . All had poor construct validity . The PEM was the easiest to underst and and complete , taking the least time . Correlation between the scales is high and conversion equations were calculated . All three are reliable and reproducible patient completed question naires , but the PEM is the easiest to use . The validity of all is suspected for nerve disorders Objective To assess which are the clinical examination tests that are more related to quality of life ( QoL ) , depression , and disability in CMT patients . Design Large prospect i ve multicenter study through the use of vali date d clinical , disability , and QoL measurements . Correlations between clinical pattern and disability/QoL and depression were studied . Setting Departments of Neurology . Patients and participants 211 CMT patients ( 60 % females , mean age 42.5 years ) . Interventions None . Measurements and results Sensory function was related to both mental and physical aspects of patient ’s QoL. Ability to walk on toes and heels was related to physical aspects of QoL/disability but also to bodily pain . Strength of forearm/h and intrinsic muscles was related to disability and physical aspects of QoL. Conclusions Some clinical tests may be better outcome measures than others because they are related to aspects of life highly relevant to the patients . This information may be useful in clinical practice and in clinical trials to infer the patient ’s In this study , the intra- and interobserver reliability of the Semmes-Weinstein monofilaments ( SWMFs ) was determined in the h and s of 15 patients with Charcot-Marie-Tooth disease . In addition , the amount and distribution of sensory loss in the h and , and the relation between sensory loss , intrinsic muscle strength , and h and dexterity was explored in 45 patients .  SWMF testing had good intra- and interobserver reliability with intraclass correlation coefficients of 0.91 and 0.86 , respectively . The SWMF testing revealed normal sensory function in 43 % of all six locations . The average loss of the intrinsic h and muscle strength was 57 % . Poor strength was found in patients with both poor and with good sensory function . The correlation between the measurements of intrinsic muscle strength and the Sollerman test for dexterity was 0.70 & NA ; The clinical diagnosis of Complex Regional Pain Syndrome ( CRPS ) is a dichotomous ( yes/no ) categorization necessary for clinical decision‐making . However , such dichotomous diagnostic categories do not convey an individual 's subtle and temporal gradations in severity of the condition , and have poor statistical power when used as an outcome measure in research . This study evaluated the validity and potential utility of a continuous type score to index severity of CRPS . Psychometric and medical evaluations were conducted in 114 CRPS patients and 41 non‐CRPS neuropathic pain patients . Based on the presence/absence of 17 clinical ly‐assessed signs and symptoms of CRPS , an overall CRPS Severity Score ( CSS ) was derived . The CSS discriminated well between CRPS and non‐CRPS patients ( p < .001 ) , and displayed strong associations with dichotomous CRPS diagnoses using both IASP diagnostic criteria ( Eta = 0.69 ) and proposed revised criteria ( Eta = 0.77–0.88 ) . Higher CSS was associated with significantly higher clinical pain intensity , distress , and functional impairments , as well as greater bilateral temperature asymmetry and thermal perception abnormalities ( p ’s < .05 ) . In an archival prospect i ve data set , increases in anxiety and depression from pre‐surgical baseline to 4 weeks post‐knee arthroplasty were found to predict significantly higher CSS at 6‐ and 12‐month follow‐up ( p ’s < .05 ) . Results indicate the CSS corresponds with and complements currently accepted dichotomous diagnostic criteria for CRPS , and support its validity as an index of CRPS severity . Its utility as an outcome measure in research studies is also suggested , with potential statistical advantages over dichotomous diagnostic criteria & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Objectives To describe the interference of herpes zoster ( HZ ) pain and discomfort with activities of daily living ( ADLs ) and health-related quality of life ( HRQL ) during the acute rash phase , and to quantify the relationship between acute HZ pain and discomfort and impaired ADLs and HRQL in older persons . Methods Prospect i ve , observational study of 160 HZ out patients age ≥60 at 4 US study sites who completed the Zoster Brief Pain Inventory ( ZBPI ) , Zoster Impact Question naire ( ZIQ ) , McGill Pain Question naire , EuroQol , and SF-12 question naires on a predetermined schedule . Patients rated interference on a 0 to 10 scale for ADL items in the ZBPI and the ZIQ . Interference scores were averaged to create summary measures for the ZBPI items ( ZBPI ADLI ) and ZIQ items ( ZIQ ADLI ) . A composite pain score was used in mixed-effects models analyses of the association between pain and discomfort and ADLI and HRQL measures during the first 35 days after HZ rash onset . Results HZ pain interfered with all ADLs but interference was greatest for enjoyment of life , sleep , general activity , leisure activities , getting out of the house , and shopping . For every 1.0 point increase in pain and discomfort intensity , there was a 0.69 and 0.53 point increase in ZBPI and ZIQ interference , respectively , and a 2.81 point , 1.57 point , and 1.95 point decrease in EuroQol , SF-12 physical , and SF-12 mental scales , respectively . Discussion Acute zoster pain and discomfort has a significant negative impact on functional status and HRQL in older adults . The magnitude of interference increases with increasing pain and discomfort intensity ABSTRACT The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non‐neuropathic pain that can be used in studies of epidemiology , natural history , pathophysiologic mechanisms , and treatment response . We exp and ed and revised the Short‐form McGill Pain Question naire1 ( SF‐MPQ ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0–10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials . The reliability , validity , and subscale structure of the revised SF‐MPQ ( SF‐MPQ‐21 )  were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a r and omized clinical trial . The data suggest that the SF‐MPQ‐2 has excellent reliability and validity , and the results of both exploratory and confirmatory factor analyses provided support for four readily interpretable subscales — continuous pain , intermittent pain , predominantly neuropathic pain , and affective descriptors . These results provide a basis for use of the SF‐MPQ‐2 in future clinical research , including clinical trials of treatments for neuropathic and non‐neuropathic pain conditions UNLABELLED Data on 1,700 patients pooled from 5 r and omized , placebo-controlled duloxetine studies ( 3 in diabetic peripheral neuropathic pain and 2 in fibromyalgia ) were analyzed to determine clinical ly important differences ( CIDs ) in the 0 to 10 Numeric Rating Scale-Pain Intensity ( NRS-PI ) for patient-reported " worst " and " least " pain intensity while validating the previously published level for " average " pain . The correspondence between the baseline-to-endpoint raw and percentage change in the NRS-PI for the worst , least , and average pain were compared to patients ' perceived improvements at endpoint as measured by the 7-point Patient Global Impression of Improvement ( PGI-I ) scales . Stratification by baseline pain separated the raw but not the percent change scores . The PGI-I category of " much better " or above was our a priori definition of a CID . Cutoff points for the NRS-PI change scores were determined using a receiver operator curve analysis . A consistent relationship between the worst and average NRS-PI percent change and the PGI-I was demonstrated regardless of the study , pain type , age , sex , or treatment group with a reduction of approximately 34 % . The least pain item CID was slightly higher at 41 % . Raw change CID cutoff points were approximately -2 , -2.5 and -3 for least , average , and worst pain respectively . PERSPECTIVE We determined an anchor-based value for the change in the worst , least , and average pain intensity items of the Brief Pain Inventory that best represents a clinical ly important difference . Our findings support a st and ard definition of a clinical ly important difference in clinical trials of chronic-pain therapies Objective : To determine the validity and reliability of the  total neuropathy score ( TNS ) in normal subjects and in subjects with diabetic polyneuropathy . Background : Clinical research in peripheral neuropathy requires vali date d outcome measures . Multiple outcome measures have been used in clinical trials , including symptom measures , functional scales , quantitative clinical examinations , nerve conduction studies , computerized sensory examinations , and nerve biopsy . Each of these measures has its strengths and weaknesses . In two previous studies of toxic neuropathy from chemotherapeutic agents , the authors used the TNS as the outcome measure . The TNS combines information obtained from grading of symptoms , signs , nerve conduction studies , and quantitative sensory tests , and provides a single measure to quantify neuropathy . Methods : The authors measured the inter- and intrarater reliability of the TNS and preformed a cross-section 
    Output:
    
agent
Although a variety of pain and physical functioning outcome measures have been reported in the literature , few have demonstrate method ologically strong psychometric properties .
***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: OBJECTIVE The aim of the current study was to determine the validity of the Toronto Clinical Scoring System ( CSS ) in reflecting the presence and severity of  diabetic peripheral sensorimotor polyneuropathy ( DSP )  as determined by myelinated fiber density ( FD ) on sural nerve biopsy . RESEARCH DESIGN AND METHODS Eighty-nine patients with both type 1 and type 2 diabetes , ascertained from a large therapeutic r and omized controlled trial , were included in this cross-sectional , observational cohort study . Morphological severity of DSP was expressed as the FD in the sural nerve biopsy . The Toronto CSS was applied to all patients to determine a clinical neuropathy score . General linear regression models were used to assess the relationship between the morphological severity of DSP and the Toronto CSS .  RESULTS The Toronto CSS showed a significant negative correlation with sural nerve FD ( R(2 ) = 0.256 , P < 0.0001 ) . The Toronto CSS was lower in those with better glycemic control ( HbA(1c ) < /=8 % ) . Sural nerve FD and the Toronto CSS showed strong correlations with electrophysiology , by both summed amplitude and summed conduction velocity values . CONCLUSIONS The Toronto CSS is a valid instrument to reflect the presence and severity of DSP as measured by sural nerve morphology and electrophysiology . The results of the current study underscore the interrelationships between clinical deficits , electrophysiological findings , and morphological changes in DSP . This evidence suggests that the Toronto CSS may prove useful in documenting and monitoring DSP in the clinic and in clinical research trials The  Patient Evaluation Measure ( PEM ) , The  Michigan H and Outcome Question naire ( MHQ )  and the Disabilities of the Arm , Shoulder and H and ( DASH ) score were assessed independent of their originators for reliability , construct and criterion validity and acceptability , using an ease of use question naire . These were administered in r and om order to 100 patients with different h and and wrist disorders and with different impairments of movement , pain , sensation and strength . The internal consistency of all three question naires was very high suggesting redundancy in the questions . All question naires were reproducible and valid for finger and wrist disorders , but less for nerve disorders . All had poor construct validity . The PEM was the easiest to underst and and complete , taking the least time . Correlation between the scales is high and conversion equations were calculated . All three are reliable and reproducible patient completed question naires , but the PEM is the easiest to use . The validity of all is suspected for nerve disorders Objective To assess which are the clinical examination tests that are more related to quality of life ( QoL ) , depression , and disability in CMT patients . Design Large prospect i ve multicenter study through the use of vali date d clinical , disability , and QoL measurements . Correlations between clinical pattern and disability/QoL and depression were studied . Setting Departments of Neurology . Patients and participants 211 CMT patients ( 60 % females , mean age 42.5 years ) . Interventions None . Measurements and results Sensory function was related to both mental and physical aspects of patient ’s QoL. Ability to walk on toes and heels was related to physical aspects of QoL/disability but also to bodily pain . Strength of forearm/h and intrinsic muscles was related to disability and physical aspects of QoL. Conclusions Some clinical tests may be better outcome measures than others because they are related to aspects of life highly relevant to the patients . This information may be useful in clinical practice and in clinical trials to infer the patient ’s In this study , the intra- and interobserver reliability of the Semmes-Weinstein monofilaments ( SWMFs ) was determined in the h and s of 15 patients with Charcot-Marie-Tooth disease . In addition , the amount and distribution of sensory loss in the h and , and the relation between sensory loss , intrinsic muscle strength , and h and dexterity was explored in 45 patients .  SWMF testing had good intra- and interobserver reliability with intraclass correlation coefficients of 0.91 and 0.86 , respectively . The SWMF testing revealed normal sensory function in 43 % of all six locations . The average loss of the intrinsic h and muscle strength was 57 % . Poor strength was found in patients with both poor and with good sensory function . The correlation between the measurements of intrinsic muscle strength and the Sollerman test for dexterity was 0.70 & NA ; The clinical diagnosis of Complex Regional Pain Syndrome ( CRPS ) is a dichotomous ( yes/no ) categorization necessary for clinical decision‐making . However , such dichotomous diagnostic categories do not convey an individual 's subtle and temporal gradations in severity of the condition , and have poor statistical power when used as an outcome measure in research . This study evaluated the validity and potential utility of a continuous type score to index severity of CRPS . Psychometric and medical evaluations were conducted in 114 CRPS patients and 41 non‐CRPS neuropathic pain patients . Based on the presence/absence of 17 clinical ly‐assessed signs and symptoms of CRPS , an overall CRPS Severity Score ( CSS ) was derived . The CSS discriminated well between CRPS and non‐CRPS patients ( p < .001 ) , and displayed strong associations with dichotomous CRPS diagnoses using both IASP diagnostic criteria ( Eta = 0.69 ) and proposed revised criteria ( Eta = 0.77–0.88 ) . Higher CSS was associated with significantly higher clinical pain intensity , distress , and functional impairments , as well as greater bilateral temperature asymmetry and thermal perception abnormalities ( p ’s < .05 ) . In an archival prospect i ve data set , increases in anxiety and depression from pre‐surgical baseline to 4 weeks post‐knee arthroplasty were found to predict significantly higher CSS at 6‐ and 12‐month follow‐up ( p ’s < .05 ) . Results indicate the CSS corresponds with and complements currently accepted dichotomous diagnostic criteria for CRPS , and support its validity as an index of CRPS severity . Its utility as an outcome measure in research studies is also suggested , with potential statistical advantages over dichotomous diagnostic criteria & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Objectives To describe the interference of herpes zoster ( HZ ) pain and discomfort with activities of daily living ( ADLs ) and health-related quality of life ( HRQL ) during the acute rash phase , and to quantify the relationship between acute HZ pain and discomfort and impaired ADLs and HRQL in older persons . Methods Prospect i ve , observational study of 160 HZ out patients age ≥60 at 4 US study sites who completed the Zoster Brief Pain Inventory ( ZBPI ) , Zoster Impact Question naire ( ZIQ ) , McGill Pain Question naire , EuroQol , and SF-12 question naires on a predetermined schedule . Patients rated interference on a 0 to 10 scale for ADL items in the ZBPI and the ZIQ . Interference scores were averaged to create summary measures for the ZBPI items ( ZBPI ADLI ) and ZIQ items ( ZIQ ADLI ) . A composite pain score was used in mixed-effects models analyses of the association between pain and discomfort and ADLI and HRQL measures during the first 35 days after HZ rash onset . Results HZ pain interfered with all ADLs but interference was greatest for enjoyment of life , sleep , general activity , leisure activities , getting out of the house , and shopping . For every 1.0 point increase in pain and discomfort intensity , there was a 0.69 and 0.53 point increase in ZBPI and ZIQ interference , respectively , and a 2.81 point , 1.57 point , and 1.95 point decrease in EuroQol , SF-12 physical , and SF-12 mental scales , respectively . Discussion Acute zoster pain and discomfort has a significant negative impact on functional status and HRQL in older adults . The magnitude of interference increases with increasing pain and discomfort intensity ABSTRACT The objective of the present research was to develop a single measure of the major symptoms of both neuropathic and non‐neuropathic pain that can be used in studies of epidemiology , natural history , pathophysiologic mechanisms , and treatment response . We exp and ed and revised the Short‐form McGill Pain Question naire1 ( SF‐MPQ ) pain descriptors by adding symptoms relevant to neuropathic pain and by modifying the response format to a 0–10 numerical rating scale to provide increased responsiveness in longitudinal studies and clinical trials . The reliability , validity , and subscale structure of the revised SF‐MPQ ( SF‐MPQ‐21 )  were examined in responses from 882 individuals with diverse chronic pain syndromes and in 226 patients with painful diabetic peripheral neuropathy who participated in a r and omized clinical trial . The data suggest that the SF‐MPQ‐2 has excellent reliability and validity , and the results of both exploratory and confirmatory factor analyses provided support for four readily interpretable subscales — continuous pain , intermittent pain , predominantly neuropathic pain , and affective descriptors . These results provide a basis for use of the SF‐MPQ‐2 in future clinical research , including clinical trials of treatments for neuropathic and non‐neuropathic pain conditions UNLABELLED Data on 1,700 patients pooled from 5 r and omized , placebo-controlled duloxetine studies ( 3 in diabetic peripheral neuropathic pain and 2 in fibromyalgia ) were analyzed to determine clinical ly important differences ( CIDs ) in the 0 to 10 Numeric Rating Scale-Pain Intensity ( NRS-PI ) for patient-reported " worst " and " least " pain intensity while validating the previously published level for " average " pain . The correspondence between the baseline-to-endpoint raw and percentage change in the NRS-PI for the worst , least , and average pain were compared to patients ' perceived improvements at endpoint as measured by the 7-point Patient Global Impression of Improvement ( PGI-I ) scales . Stratification by baseline pain separated the raw but not the percent change scores . The PGI-I category of " much better " or above was our a priori definition of a CID . Cutoff points for the NRS-PI change scores were determined using a receiver operator curve analysis . A consistent relationship between the worst and average NRS-PI percent change and the PGI-I was demonstrated regardless of the study , pain type , age , sex , or treatment group with a reduction of approximately 34 % . The least pain item CID was slightly higher at 41 % . Raw change CID cutoff points were approximately -2 , -2.5 and -3 for least , average , and worst pain respectively . PERSPECTIVE We determined an anchor-based value for the change in the worst , least , and average pain intensity items of the Brief Pain Inventory that best represents a clinical ly important difference . Our findings support a st and ard definition of a clinical ly important difference in clinical trials of chronic-pain therapies Objective : To determine the validity and reliability of the  total neuropathy score ( TNS ) in normal subjects and in subjects with diabetic polyneuropathy . Background : Clinical research in peripheral neuropathy requires vali date d outcome measures . Multiple outcome measures have been used in clinical trials , including symptom measures , functional scales , quantitative clinical examinations , nerve conduction studies , computerized sensory examinations , and nerve biopsy . Each of these measures has its strengths and weaknesses . In two previous studies of toxic neuropathy from chemotherapeutic agents , the authors used the TNS as the outcome measure . The TNS combines information obtained from grading of symptoms , signs , nerve conduction studies , and quantitative sensory tests , and provides a single measure to quantify neuropathy . Methods : The authors measured the inter- and intrarater reliability of the TNS and preformed a cross-section 
    Output:
    