***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: AIMS Disagreement exists on effective and sensitive outcome measures in neuropathy associated with impaired glucose tolerance ( IGT ) . Nerve conduction studies and skin biopsies are costly , invasive and may have their problems with reproducibility and clinical applicability . A clinical measure of neuropathy that has sufficient sensitivity and correlates to invasive measures would enable significant future research . METHODS Data was collected prospect ively on patients with IGT and symptomatic early neuropathy ( neuropathy symptoms < 2years ) and normal controls . The seven scales that were examined were the  Neuropathy Impairment Score of the Lower Limb ( NIS-LL ) , Michigan Diabetic Neuropathy Score ( MNDS ) , modified Toronto Clinical Neuropathy Scale ( mTCNS ) , Total Neuropathy Score ( Clinical ) ( TNSc ) , The Utah Early Neuropathy Scale ( UENS ) , the Early Neuropathy Score ( ENS ) , and the Neuropathy Disability Score ( NDS ) . RESULTS All seven clinical scales were determined to be excellent in discriminating between patients with neuropathy from controls without neuropathy . The strongest discrimination was seen with the mTCNS . The best sensitivity and specificity for the range of scores obtained , as determined by using receiver operating characteristic curves , was seen for the mTCNS followed by the TNSc . Most scales show a stronger correlation with measures of large rather than small fiber neuropathy . CONCLUSIONS All seven scales identify patients with neuropathy . For the purpose of screening potential patients for a clinical study , the mTCNS followed by the TNSc would be most helpful to select patients with neuropathy Goals The aim of the study was to determine the feasibility and validity of a newly developed patient-based instrument — the  Patient Neurotoxicity Question naire (PNQ)—for grading chemotherapy-induced peripheral neuropathy ( CIPN ) . Patients and methods We prospect ively collected data from 300 female patients who were treated with taxane chemotherapy for primary breast cancer as part of a national multicenter phase III r and omized trial ( N-SAS BC 02 ) . We evaluated patient compliance with the PNQ and several validation parameters , including concordance between CIPN grade s noted by physicians ( National Cancer Institute Common Toxicity Criteria ) and patients ( PNQ ) , and the concurrent validity and responsiveness of the PNQ versus the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity ( FACT/GOG-Ntx ) utilizing data at pre-treatment and before three , five , and seven treatment cycles . Main results The question naire completion rate was > 90 % at all assessment s. Evaluation by physicians always result ed in lower neuropathy assessment scores compared with those reported directly by patients ( weighted kappa coefficients , 0.02–0.06 ) . Both PNQ sensory and motor scores were significantly correlated with the FACT/GOG-Ntx ( r = 0.66 and 0.51 , respectively ) . In the repeated measures analysis of variance model , PNQ grade s increased considerably as treatment continued , indicating progressively worsening CIPN over time . Conclusions The PNQ has an applicable degree of feasibility and validity , useful for the diagnosis of CIPN as well as for clinical treatment decision-making , where the development of CIPN is a potential treatment-limiting consideration . Physicians underreport and underestimate the severity of CIPN symptoms compared with patients , thereby supporting the importance of assessing patient-reported outcomes using the PNQ IMPORTANCE Familial amyloid polyneuropathy , a lethal genetic disease caused by aggregation of variant transthyretin , induces progressive peripheral nerve deficits and disability . Diflunisal , a nonsteroidal anti-inflammatory agent , stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro . OBJECTIVE To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy . DESIGN , SETTING , AND PARTICIPANTS International r and omized , double-blind , placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinical ly detectable peripheral or autonomic neuropathy at amyloid centers in Sweden ( Umeå ) , Italy ( Pavia ) , Japan ( Matsumoto and Kumamoto ) , Engl and ( London ) , and the United States ( Boston , Massachusetts ; New York , New York ; and Rochester , Minnesota ) from 2006 through 2012 . INTERVENTION Participants were r and omly assigned to receive diflunisal , 250 mg ( n=64 ) , or placebo ( n=66 ) twice daily for 2 years . MAIN OUTCOMES AND MEASURES The primary end point , the difference in polyneuropathy progression between treatments , was measured by the Neuropathy Impairment Score plus 7 nerve tests ( NIS+7 ) which ranges from 0 ( no neurological deficits ) to 270 points ( no detectable peripheral nerve function ) . Secondary outcomes included a quality -of-life question naire ( 36-Item Short-Form Health Survey [ SF-36 ] ) and modified body mass index . Because of attrition , we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data . RESULTS By multiple imputation , the NIS+7 score increased by 25.0 ( 95 % CI , 18.4 - 31.6 ) points in the placebo group and by 8.7 ( 95 % CI , 3.3 - 14.1 ) points in the diflunisal group , a difference of 16.3 points ( 95 % CI , 8.1 - 24.5 points ; P < .001 ) . Mean SF-36 physical scores decreased by 4.9 ( 95 % CI , -7.6 to -2.2 ) points in the placebo group and increased by 1.5 ( 95 % CI , -0.8 to 3.7 ) points in the diflunisal group ( P < .001 ) . Mean SF-36 mental scores declined by 1.1 ( 95 % CI , -4.3 to 2.0 ) points in the placebo group while increasing by 3.7 ( 95 % CI , 1.0 - 6.4 ) points in the diflunisal group ( P = .02 ) . By responder analysis , 29.7 % of the diflunisal group and 9.4 % of the placebo group exhibited neurological stability at 2 years ( < 2-point increase in NIS+7 score ; P = .007 ) . CONCLUSIONS AND RELEVANCE Among patients with familial amyloid polyneuropathy , the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life . Although longer-term follow-up studies are needed , these findings suggest benefit of this treatment for familial amyloid polyneuropathy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00294671 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-sectional validation study of the TNS and its subscales with the Mayo Clinic measures of neuropathy , neuropathy symptom score ( NSS ) , and the neurologic impairment score ( NIS ) in five healthy control subjects and 30 individuals with varying severities of diabetic polyneuropathy . Results : Inter- and intrarater reliability of the TNS  was excellent ( 0.966 and 0.986 respectively ) . The cross-sectional validation study showed excellent correlations among all measures of neuropathy . Conclusions : The total neuropathy score is a vali date d measure of peripheral nerve function and could be used as an end point for clinical trials of peripheral neuropathy The purpose of this study was to vali date the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group — Neurotoxicity ( FACT/GOG-Ntx ) question naire . The FACT/GOG-Ntx is the FACT-G plus an eleven-item subscale ( Ntx subscale ) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy . Two groups of women with ovarian cancer completed the FACT/GOG-Ntx : one group with known neurotoxicities and one group of chemotherapy-naive women newly diagnosed with ovarian cancer .  Levels of patient neuropathy , severity of toxicity , and patient quality of life from diagnosis of ovarian cancer to 12 months post-diagnosis were assessed . The Ntx subscale significantly differentiated the two groups at baseline and 3- and 6-month follow-ups , demonstrating significantly fewer problems among chemotherapy-naive patients than among patients with known neuropathy . The FACT/GOG-Ntx is a reliable and valid instrument for assessing the impact of neuropathy on health-related quality of life . The Ntx subscale demonstrated sensitivity to meaningful clinical distinctions and change over time Summary A cross-sectional multicentre study of r and omly selected diabetic patients was performed using a st and ardised question naire and examination , to establish the prevalence of peripheral neuropathy in patients attending 118 hospital diabetes clinics in the UK .  Vibration perception threshold was performed in two centres to compare with the clinical scoring systems . A total of 6487 diabetic patients were studied , 53.9 % male , median age 59 years ( range 18– 90 years ) , 37.4 % Type 1 ( insulin-dependent ) diabetes mellitus , with a median duration of diabetes 8 years ( 0–62 years ) . The overall prevalence of neuropathy was 28.5 % ( 27.4– 29.6 % ) ( 95 % confidence interval ) in this population . The prevalence in Type 1 diabetic patients was 22.7 % ( 21.0– 24.4 % ) and in Type 2 ( non-insulin-dependent ) diabetic patients it was 32.1 % ( 30.6–33.6 % ) . The prevalence of diabetic peripheral neuropathy increased with age , from 5 % ( 3.1– 6.9 % ) in the 20–29 year age group to 44.2 % ( 41.1–47.3 % ) in the 70–79 year age group . Neuropathy was associated with duration of diabetes , and was present in 20.8 % ( 19.1–22.5 % ) of patients with diabetes duration less than 5 years and in 36.8 % ( 34.9–38.7 % ) of those with diabetes duration greater than 10 years . Mean vibration perception threshold measured at the great toe was 21.1±13.5 SD volts and correlated with the neuropathy disability score , r=0.8 p<0.001 . In conclusion , diabetic peripheral neuropathy is a common complication associated with diabetes . It increases with both age and duration of diabetes , until it is present in more than 50 % of Type 2 diabetic patients aged over 60 years . An increased awareness of the high prevalence of peripheral neuropathy , especially in older patients , should result in improved screening programmes in order to reduce the high incidence of neuropathic diabetic foot ulceration 
    Output:
    
Autonomic symptoms were less frequently included .