Objective Measures Of Disease Severity Research Articles

Computed Tomography Scans as an Objective Measure of Disease Severity in Chronic Rhinosinusitis

Objectives: A truly objective method of measuring disease severity in CRS does not exist. We evaluated computed tomography (CT) scans of chronic rhinosinusitis (CRS) patients using a novel 3-D computerized method and compared them to a 2-D objective computerized analysis of a single coronal slice through the osteomeatal complex (OMC), and subjective methods including Lund-Mackay and Zinreich’s modification of Lund-Mackay. Methods: Forty-six adults with symptoms and endoscopy confirmation of CRS underwent CT examination and received a triamcinolone injection, followed by CT scan 4-5 weeks later. Analyze software determined the 3-D total volume of inflammatory mucosal thickening in all sinuses. The triamcinolone injection served as a tool to determine each method’s sensitivity to a treatment intervention. Results: The Lin’s concordance class correlation (CCC) of the OMC method revealed the best correlation to the 3-D volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund-Mackay methods (0.824). Post-treatment results demonstrated that both the OMC (0.824) and Zinreich’s (0.778) methods had strong agreement with the 3-D volumetric methods and were very sensitive to change, whereas the Lund-Mackay (0.545) only had moderate agreement. Conclusions: Computerized CT analysis provides the most comprehensive, objective, and reproducible method of measuring disease severity and is very sensitive to change induced by treatment intervention. A 2-D coronal image through the OMC provides a valid, user-friendly method of assessing CRS and is representative of CRS severity in all sinuses. Zinreich’s subjective method correlated well overall, but Lund-Mackay lagged behind in disease representation and sensitivity to change.

Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis

Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain. In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA symptom severity. Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged. These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.

Multicenter assessment of the repeatability and reproducibility of the revised Venous Clinical Severity Score (rVCSS).

The Venous Clinical Severity Score (VCSS) was designed and validated as an objective measure of disease severity in patients with chronic venous disease (CVD). Recently, a revision of the VCSS (rVCSS) was performed to resolve ambiguity in the clinical descriptors and improve clarity and ease of use. This new revised VCSS requires validation to determine its repeatability and reproducibility in clinical evaluation of patients with varying levels of CVD. A prospective multicenter protocol was designed to enroll patients undergoing evaluation for CVD at venous practices with experience using the original VCSS. At the time of initial evaluation, two clinicians independently assessed both lower extremities to determine the rVCSS and the CEAP clinical score. Between 1 and 6 weeks, patients returned and received repeat assessment of the rVCSS by the same two clinicians independently. Patients were excluded if any venous intervention occurred between the two separate evaluation visits. Scores were compared to determine inter- and intra-observer variability overall and within each CEAP clinical class. Seven centers enrolled a total of 136 limbs yielding 248 paired evaluations for interobserver variability and 258 paired evaluations for intraobserver variability. The mean interobserver rVCSS difference was 1.4± 1.7 and the mean intraobserver variability was 1.3± 1.6. Statistical assessment with weighted kappa yielded good repeatability (κ= 0.68; P<.0001) and good reproducibility (κ= 0.72; P< .000001) for the rVCSS. The rVCSS correlated well with the CEAP clinical class with significant differences between rVCSS in increasing classes. (P< .0001). In this multicenter evaluation, the rVCSS was demonstrated to be a reliable and reproducible instrument for documentation of the severity of symptoms in patients with lower extremity venous insufficiency.

The Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-revised (PISQ-IR)

Pelvic floor disorders greatly affect the lives of women who suffer from them. Whereas objective measures of disease severity are essential in the evaluation of these disorders, measures of symptom severity, quality of life, and function provide a broader and more comprehensive representation of the impact these disorders have on women’s lives. Furthermore, they are critical for evaluating the impact of treatment on day-to-day life. The use of questionnaires to assess outcomes in urogynecology has been increasing. Originally, subjective outcomes were often assessed by simply asking the patient what and how bothersome their symptoms were and whether symptoms had resolved and function returned after treatment. Although central to clinical care, the weaknesses of measuring subjective outcomes in this manner for research are obvious, including lack of reproducibility, bias on the part of the provider in response interpretation, and lack of ability to compare outcomes across individuals and over time. To address these problems, standardized, multidimensional questionnaires are often used. In scale development, the goal is to develop a questionnaire that captures concerns that are central to both patients and providers, that measures concerns in a meaningful way, that is reproducible within individuals and across populations, and that is developed so that valid inferences with meaning to clinical and personal evaluation about status and function can be drawn [1]. In the past two decades, an array of valid and reliable condition-specific measures of pelvic floor function has been developed. These measures represented a large improvement over ad hoc questioning and are widely used in both research and clinical settings. Nonetheless, there is still much work to do to improve these tools, particularly with respect to their international use. The Pelvic Organ Prolapse Incontinence Sexual Questionnaire (PISQ) is the primary measure used to assess sexual function in women with urinary incontinence and prolapse, yet the original measure had deficits [2, 3]. The International Urinary Gynecological Association (IUGA) Sexual Function Working Group aimed to conduct a fullscale re-evaluation of the PISQ, with the goals of refining its measurement properties, enhancing the ability to assess outcomes in women who are not sexually active and in women with anal incontinence, and developing an instrument ultimately intended for international use [4]. These goals have been realized in the development of the PISQ-IR. The new measure is not just a refinement of items found in the PISQ but includes new approaches to assessing the inherent diversity of women with pelvic floor disorders (PFD), such as gender-neutral items, to assess the impact of partner on sexual function. Importantly, this study was designed with input from a team of urogynecologists from around the world, from item development to evaluation and determination of the content of the final scales, with the explicit goal of having an instrument that was directed toward international usage from inception. In this issue of the International Urogynecology Journal, we present the validity, reliability, and responsiveness of this new measure: the PISQ-IR [5]. In a companion article, we further present data explaining PISQ-IR scale creation and R. G. Rogers (*) Department of Obstetrics and Gynecology and Surgery, University of New Mexico Health Sciences Center, Albuquerque, NM 87110, USA e-mail: RRogers@salud.unm.edu

Grading severity in retinitis pigmentosa using clinical assessment, visual acuity, perimetry and optical coherence tomography

To develop a grading system for retinitis pigmentosa (RP), providing clinicians with a simple, objective measure of disease severity. An observational case series of 14 patients with RP. Disease severity was assessed using four criteria; clinical appearance, visual acuity (best corrected LogMAR, BCVA), perimetry (mean deviation, MD) and Fourier-domain optical coherence tomography (outer retinal thickness, ORT at the fovea). Each criterion was scored on a severity scale from 0 (mild disease) to 4 (severe disease), giving an overall score out of 16. The mean BCVA was 0.37 LogMAR (range 0.02 to PL), mean MD was -25.35 dB (range -7.48 to -34.38 dB), mean retinal thickness at the fovea was 189.4 μm (range 96.5-264.5 μm) and mean ORT at the fovea was 140.6 μm (range 63.4-193.4 μm). The clinical appearance correlated well with each of the quantitative measures of disease severity; BCVA (0.62, p = 0.022), MD (-0.903, p < 0.0001) and ORT (-0.698, p = 0.005). Applying the grading system to our patients, the severity scores were evenly spread between grades 1 and 14. We present a simple, objective grading system for RP offering a potential tool for grading disease severity with applications such as assessing progression, comparing patient populations and measuring outcomes in clinical trials.

Quantifying the eyeball test: Sarcopenia, analytic morphomics, and liver transplantation

The physiological implications of end-stage liver disease (ESLD) are so pervasive that measuring the severity of the disease is challenging and imperfect. Although the Model for End-Stage Liver Disease (MELD) score is convenient and reliable, clinicians appreciate the broad range of disease severity among patients with any given MELD score. Within this context, most MELD-based allocation systems allow exception points for patients whose risk of wait-list mortality is poorly reflected by their calculated MELD scores. In the United States, the majority of MELD exceptions are granted for objective diagnoses such as hepatocellular carcinoma and hepatopulmonary syndrome, and patients who are subjectively assessed to be ‘‘sicker than their MELD score’’ likely have increased wait-list mortality. Importantly, allocation policy and treatment algorithms work best with objective clinical assessments (eg, the MELD score), which are well suited for standardization and the rigorous modeling of predicted risk. In all, better objective measures of disease severity in patients with liver disease are needed. One such objective measure of disease severity, sarcopenia, is described by Tandon et al. 1 in this issue of Liver Transplantation. This good work has several key take-home points. First, the authors demonstrate that sarcopenia is a strong and independent predictor of mortality among patients waiting for liver transplanta

Evaluation of a Clinical Dehydration Scale in Children Requiring Intravenous Rehydration

OBJECTIVES: To evaluate the reliability and validity of a previously derived clinical dehydration scale (CDS) in a cohort of children with gastroenteritis and evidence of dehydration. METHODS: Participants were 226 children older than 3 months who presented to a tertiary care emergency department and required intravenous rehydration. Reliability was assessed at treatment initiation, by comparing the scores assigned independently by a trained research nurse and a physician. Validity was assessed by using parameters reflective of disease severity: weight gain, baseline laboratory results, willingness of the physician to discharge the patient, hospitalization, and length of stay. RESULTS: Interobserver reliability was moderate, with a weighted κ of 0.52 (95% confidence interval [CI] 0.41, 0.63). There was no correlation between CDS score and percent weight gain, a proxy measure of fluid deficit (Spearman correlation coefficient = −0.03; 95% CI −0.18, 0.12). There were, however, modest and statistically significant correlations between CDS score and several other parameters, including serum bicarbonate (Pearson correlation coefficient = −0.35; 95% CI −0.46, −0.22) and length of stay (Pearson correlation coefficient = 0.24; 95% CI 0.11, 0.36). The scale’s discriminative ability was assessed for the outcome of hospitalization, yielding an area under the receiver operating characteristic curve of 0.65 (95% CI 0.57, 0.73). CONCLUSIONS: In children administered intravenous rehydration, the CDS was characterized by moderate interobserver reliability and weak associations with objective measures of disease severity. These data do not support its use as a tool to dictate the need for intravenous rehydration or to predict clinical course. * Abbreviations: AUC — : area under the curve CDS — : clinical dehydration scale CI — : confidence interval ED — : emergency department IQR — : interquartile range ROC — : receiver operating characteristic

Evaluation of a Clinical Dehydration Scale in Children Requiring Intravenous Rehydration

To evaluate the reliability and validity of a previously derived clinical dehydration scale (CDS) in a cohort of children with gastroenteritis and evidence of dehydration. Participants were 226 children older than 3 months who presented to a tertiary care emergency department and required intravenous rehydration. Reliability was assessed at treatment initiation, by comparing the scores assigned independently by a trained research nurse and a physician. Validity was assessed by using parameters reflective of disease severity: weight gain, baseline laboratory results, willingness of the physician to discharge the patient, hospitalization, and length of stay. Interobserver reliability was moderate, with a weighted κ of 0.52 (95% confidence interval [CI] 0.41, 0.63). There was no correlation between CDS score and percent weight gain, a proxy measure of fluid deficit (Spearman correlation coefficient = -0.03; 95% CI -0.18, 0.12). There were, however, modest and statistically significant correlations between CDS score and several other parameters, including serum bicarbonate (Pearson correlation coefficient = -0.35; 95% CI -0.46, -0.22) and length of stay (Pearson correlation coefficient = 0.24; 95% CI 0.11, 0.36). The scale's discriminative ability was assessed for the outcome of hospitalization, yielding an area under the receiver operating characteristic curve of 0.65 (95% CI 0.57, 0.73). In children administered intravenous rehydration, the CDS was characterized by moderate interobserver reliability and weak associations with objective measures of disease severity. These data do not support its use as a tool to dictate the need for intravenous rehydration or to predict clinical course.

Long-Term Use of Hydroxypropyl Cellulose Ophthalmic Insert to Relieve Symptoms of Dry Eye in a Contact Lens Wearer: Case-Based Experience

To report a case in which hydroxypropyl cellulose ophthalmic inserts were successfully used for the treatment of dry eye disease in a contact lens (CLs) wearer for more than 25 years. Review of clinical findings in a female CL wearer with dry eye spanning more than 30 years. The patient was diagnosed with the Sjögren syndrome and demonstrated inadequate lacrimation as assessed by Schirmer testing. Slitlamp examination demonstrated bilateral corneal stippling with fluorescein and signs of superior limbic keratoconjunctivitis. Initially, the patient's symptoms improved with infrequent use of artificial tears. As the signs and symptoms of dry eye disease worsened, the patient initiated therapy with once-daily hydroxypropyl cellulose ophthalmic inserts. Punctal plugs and updating to increasingly oxygen-permeable soft CLs, in combination with continued use of the inserts, largely controlled the signs and symptoms of dry eye disease during a 25-year period. Simultaneous use of the hydroxypropyl cellulose ophthalmic inserts and CLs was well tolerated without any significant side effects or changes in visual acuity. Dry eye is a chronic disease often requiring long-term management. In this case, daily use of hydroxypropyl cellulose ophthalmic inserts effectively treated autoimmune dry eye, providing symptomatic relief, and resulted in improved objective measures of disease severity across several decades. Such an experience is consistent with the available evidence-based data for hydroxypropyl cellulose ophthalmic inserts and supports their use in clinical practice for the treatment of moderate-to-severe dry eye disease.

T2 Mapping in Duchenne Muscular Dystrophy: Distribution of Disease Activity and Correlation with Clinical Assessments

To analyze T2 maps of pelvic and thigh muscles in Duchenne muscular dystrophy (DMD), to identify the most severely affected muscle, and to correlate the T2 of muscle with the grade of fatty infiltration at nonquantitative magnetic resonance (MR) imaging and results of clinical assessment. This prospective study was HIPAA compliant and was approved by the institutional review board; written consent was obtained from all participants' parents or guardians. Thirty-four boys with DMD (mean age, 8.4 years) were evaluated clinically (age, clinical function score, timed Gower score, time to run 30 feet, and serum creatine kinase [CK] level) and with nonquantitative MR imaging and axial T2 mapping from the iliac crest to the mid thigh. The T2 maps and mean T2 of 18 muscles in the pelvis and thighs were analyzed to identify the most severely involved muscle. The amount of fatty infiltration was assigned a grade of zero to four for all pelvic and thigh muscles by using T1-weighted nonquantitative MR images. The Spearman correlation coefficients model was used to correlate the mean T2, nonquantitative MR imaging score and clinical assessments. The gluteus maximus muscle had the highest T2. The mean T2 for this muscle showed a significant correlation with the nonquantitative MR imaging score for fatty infiltration (P < .001) and with all clinical assessments except CK level. Gluteus maximus muscles are most severely affected in patients with DMD. The T2 of the gluteus maximus muscle can be used as a quantitative and objective measure of disease severity.

British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009

St John’s Institute of Dermatology, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT U.K. *Department of Dermatology, Royal Gwent Hospital, Newport NP20 2UB, U.K. Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. The Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, U.K. §Psoriasis and Psoriatic Arthritis Alliance, PO Box 111, St Albans AL2 3JQ, U.K. –Department of Dermatology, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, U.K. **Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, U.K. §§Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, U.K.

Visual vigilance in drivers with obstructive sleep apnea

Objective To determine the effects of obstructive sleep apnea (OSA) on visual vigilance during simulated automobile driving. Methods Twenty-five drivers with OSA and 41 comparison drivers participated in an hour-long drive in a high-fidelity driving simulator. Drivers responded to light targets flashed at seven locations across the forward horizon. Dependent measures were percent correct [hit rate (HR)] and reaction time (RT). Self-assessment of sleepiness used the Stanford Sleepiness Scale (SSS) before and after the drive and the Epworth Sleepiness Scale (ESS). Results OSA drivers showed reduced vigilance based on lower HR than comparison drivers, especially for peripheral targets (80.7±14.8% vs. 86.7±8.8%, P=.03). OSA drivers were sleepier at the end of the drive than comparison drivers (SSS=4.2±1.2 vs. 3.6±1.2, P=.03), and increased sleepiness correlated with decreased HR only in those with OSA ( r=−0.49, P=.01). Lower HR and higher post-drive SSS predicted greater numbers of driving errors in all subjects. Yet, ESS, predrive SSS, and most objective measures of disease severity failed to predict driving and vigilance performance in OSA. Conclusions Reduced vigilance for peripheral visual targets indicates that OSA drivers have restriction of their effective field of view, which may partly explain their increased crash risk. This fatigue-related decline in attention is predicted by increased subjective sleepiness during driving. These findings may suggest a means of identifying and counseling high-risk drivers and aid in the development of in-vehicle alerting and warning devices.

Early oxygen uptake recovery following exercise testing in children with chronic chest diseases

The value of exercise testing as an objective measure of disease severity in patients with chronic chest diseases (CCD) is becoming increasingly recognized. The aim of this study was to investigate changes in oxygen uptake (VO2) during early recovery following maximal cardiopulmonary exercise testing (CPXT) in relation to functional capacity and markers of disease severity. Twenty-seven children with CCD (age 12.7 +/- 3.1 years; 17 female) [19 children with Cystic fibrosis (CF) (age 13.4 +/- 3.1 years; 10 female) and 8 with other stable non-CF chest diseases (NON-CF) (age 11.1 +/- 2.2 years; 7 female)] and 27 healthy controls (age 13.2 +/- 3.3 years; 17 female) underwent CPXT on a cycle ergometer. On-line respiratory gas analysis measured VO2 before and during CPXT to peak VO2) (VO2(peak)), and during the first 10 min of recovery. Early VO2 recovery was quantified by the time (sec) to reach 50% of the VO2 (peak) value. Early VO2 recovery was correlated against spirometry [forced expiratory volume in 1 sec (FEV(1)) and forced expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75))] and aerobic fitness (VO2)(peak)) as a measure of functional capacity. Disease severity was graded in the CF patients by the Shwachman score (SS). Compared to controls, children with CCD demonstrated a significantly reduced VO2(peak) (P = 0.011), FEV(1) (P < 0.001), FEF(25-75) (P < 0.001), and a significantly prolonged early (VO2) recovery (P = 0.024). In the CF patients the SS was significantly correlated with early VO2 recovery (r = -0.63, P = 0.004), FEV(1) (r = 0.72, P = 0.001), and FEF(25-75) (r = 0.57, P = 0.011). In the children with CCD, FEV(1), FEF(25-75), and BMI were not significantly correlated with VO2(peak) or early VO2 recovery. Lung function does not necessarily reflect aerobic fitness and the ability to recover from exercise in these patients. A significant relationship was found between VO2(peak) and early VO2 recovery (r = -0.39, P = 0.044) in the children with CCD, showing that a greater aerobic fitness corresponded with a faster recovery.

Depressive Symptoms and Perceived Doctor-Patient Communication in the Heart and Soul Study

BACKGROUNDDoctor-patient communication is an important marker of health-care quality. Little is known about the extent to which medical comorbidities, disease severity and depressive symptoms influence perceptions of doctor-patient communication in patients with chronic disease.METHODSIn a cross-sectional study of 703 outpatients with chronic coronary disease, we evaluated the extent to which patient reports of doctor-patient communication were influenced by medical comorbidities, disease severity and depressive symptoms. We assessed patient reports of doctor-patient communication using the Explanations of Condition and Responsiveness to Patient Preferences subscales from the “Interpersonal Processes of Care” instrument. Poor doctor-patient communication was defined as a score of <4 (range 1 to 5) on either subscale. All patients completed the nine-item Patient Health Questionnaire (PHQ) for measurement of depressive symptoms and underwent an extensive evaluation of medical comorbidities and cardiac function.RESULTSIn univariate analyses, the following patient characteristics were associated with poor reported doctor-patient communication on one or both subscales: female sex, white or Asian race and depressive symptoms. After adjusting for demographic factors, medical comorbidities and disease severity, each standard deviation (5.4-point) increase in depressive symptom score was associated with a 50% greater odds of poor reported explanations of condition (OR 1.5, 95% CI, 1.2–1.8; p < 0.001) and a 30% greater odds of poor reported responsiveness to patient preferences (OR 1.3, 95% CI, 1.1–1.5; p = 0.01). In contrast, objective measures of disease severity (left ventricular ejection fraction, exercise capacity, inducible ischemia) and medical comorbidities (hypertension, diabetes, myocardial infarction) were not associated with reports of doctor-patient communication.CONCLUSIONSIn outpatients with chronic coronary heart disease, depressive symptoms are associated with perceived deficits in doctor-patient communication, while medical comorbidities and disease severity are not. These findings suggest that patient reports of doctor-patient communication may partly reflect the psychological state of the patient.

Clinical scoring systems in cystic fibrosis

The first cystic fibrosis (CF) scoring system was published in 1958. Since then, many other scoring systems were developed. Clinical parameters, details about statistical evaluations, and recent strategic uses of scores were identified. Several similar scores aiming to assess chronic illness severity (Shwachman-Kulczycki score and a modification, Cooperman, Berneze-score and the NIH score) have not been evaluated and are out of date, given the changing natural history of CF. Of the current scoring systems, the modified Shwachman score by Doershuk is perhaps most reliable for describing follow-up studies. Scores designed for acute changes and short-term evaluation were also developed. The modified Huang score may be useful in the prognostic evaluation of patients with end-stage disease. It could also be used for discrimination of adult patients with differing disease severity and for longitudinal evaluation. Scores assessing pulmonary exacerbations could help provide consensus among clinicians regarding the need for intervention. Most of these scores require further evaluation. Although scores could provide an objective measure of disease severity, progression, need for and response to interventions, including value in selecting patients for lung transplantation and as an outcome measure for research studies, no scoring system can fulfill all these objectives. Nevertheless, there is a need for the development of a modern day longitudinal score that is sensitive, valid and reproducible, to reflect the milder disease status of patients.

The use of quantitative oculometry in the assessment of Huntington’s disease

Huntington's disease (HD) is a neurodegenerative disorder characterised by progressive motor, cognitive and psychiatric symptoms. Objective measurement of disease severity is of increasing importance for detecting symptomatic disease, as well as monitoring disease progression and the response to novel therapeutic interventions. Using a newly-developed infra-red scleral oculometer, we measured saccadic latencies and durations in HD patients exhibiting a broad range of symptoms (n=24) and control subjects of comparable ages (n=20) to see whether these parameters might reflect the presence or severity of HD. Latency distributions were characterised by creating reciprobit plots for each subject, whilst parametric statistics were applied to durations. Compared with the control group, we found the HD group had a significantly increased median latency, and early saccades were more prominent. In addition, HD patients exhibited an increased saccadic duration and variability of duration. Using Bayesian (likelihood) analysis, we obtained saccadic support values for the presence of clinical HD, which correlated with the motor Unified Huntington's Disease Rating Scale (UHDRS) score in these patients. A sensitivity/specificity analysis of all 44 participants showed that the use of this multivariate support measure was highly successful in predicting HD status, correctly diagnosing 75% of the HD patients, and (95%) of the controls; with a different criterion, these figures were 96 and 15%. Furthermore, we correctly predicted absence of disease in two additional subjects subsequently confirmed to be genetically unaffected. This strongly suggests that multivariate support values derived from saccadic parameters may provide an objective, quantitative biomarker of HD, especially the degree of motor impairment. However, larger longitudinal studies are required to determine whether they can reliably detect the earliest presymptomatic disease, or faithfully reflect disease progression.

Relationship between objective measures of peripheral arterial disease severity to self-reported quality of life in older adults with intermittent claudication

The aim of this study was to determine the relation between functional measures of peripheral arterial disease (PAD) severity with both disease-specific and generic self-reported health-related quality-of-life (HR-QOL) measures, as well as the relation between the two types of HR-QOL measures. This was a cross-sectional observation of participants from the community and primary care or vascular surgery clinics in an academic Veterans Administration medical center. Eighty patients with symptomatic Fontaine stage II PAD provided physiologic measures and self-response questionnaires. Objective measures included the ankle-brachial index (ABI), time to maximum claudication pain on a graded exercise test, and a 6-minute floor-walking distance. Self-reports included the Walking Impairment Questionnaire (WIQ), a disease-specific HR-QOL measure and the Medical Outcomes Study (MOS) Short-Form 36 (SF-36), a generic HR-QOL measure. Patients (mean age 70 +/- 8 [+/- SD] and 85% men) exhibited moderate-to-severe PAD by objective measures of ABI (0.65 +/- 0.19) and time in minutes to maximal claudication on a graded exercise test (7:54 +/- 4:58). Significant correlations were found between these measures and the WIQ distance, MOS-Physical Function, and MOS-Role Limitations due to physical dysfunction. The SF-36 and the WIQ subscales were significantly correlated. In older PAD patients with intermittent claudication, objective measures of disease severity are correlated with a self-reported, disease-specific and generic HR-QOL.

Measurement of itch using actigraphy in pediatric and adult populations

We have studied nocturnal movements using wrist-worn accelerometers in 33 adults with a range of pruritic dermatoses, 30 adult control subjects, 25 children with atopic dermatitis, and 17 pediatric control subjects. In all, 26 adults and 20 children were studied on more than one occasion, up to a maximum of 6 occasions. Participants were examined and a range of subjective measures about the extent of skin disease, itch, and quality of sleep were recorded. We show clear differences between patients and control subjects for both age groups studied, with activity medians approximately twice as high in the patients as in the control subjects ( P < .001). Studies on the same person show a considerable night-to-night variation that is unlikely to relate to measurement error, but instead, we believe, reflect genuine differences in nocturnal activity (and perhaps disease severity). Movement through the night did not seem to follow any obvious pattern. The relation between subjective measures, Severity sCORing of Atopic Dermatitis (SCORAD) index scores, and objective recorded activity was imperfect, with much unaccounted for variation. In particular, in adults, but not in children, we found a negative correlation (-0.44, P < .02) between objective movement activity and self-reported quality of sleep. Our results support the use of objective measures of scratch in the assessment of disease activity, and suggest that the relation between subjective and objective measures of disease severity may not be straightforward.

Performance characteristics of the venous clinical severity score

To facilitate study of the natural history and management of venous disease, a 10-component venous clinical severity (VCS) score has been proposed as an objective measure of disease severity. The purpose of this study was to evaluate the validity and reliability of this instrument. VCS component scores (0 to 3) for pain, varicose veins, edema, pigmentation, inflammation, induration, stocking use, and ulcer size, duration, and number were measured in consecutive patients with chronic venous disease. Differences between observers (n = 3) and on serial evaluation by the same observer were determined. One hundred twenty-eight limbs in 64 patients were evaluated. Mean VCS score increased from CEAP class 0 (1.7 +/- 1.8) to class 6 (14.7 +/- 3.0; R =.84; P <.0001). Scores in 68 limbs evaluated twice by the same observer differed by a mean of only 0.8 (P =.15), with a reliability coefficient of 0.6. Mean scores of 8.0 (+/- 5.1), 7.2 (+/- 5.1), and 8.0 (+/- 5.4) were obtained in 63 limbs evaluated by all three investigators (P =.02). Only the component scores for pain, inflammation, and pigmentation showed significant (P <.05) interobserver variability. Interobserver agreement on the absence of disease or presence of severe disease as defined by scores of 3 or less or 8 or more was good (kappa = 0.59 and 0.65, respectively). The VCS score is a critically needed tool for evaluating changes in venous disease over time. The score is reliable and shows good correlation with CEAP clinical classification.

QUALITY OF LIFE IN PATIENTS WITH AXONAL POLYNEUROPATHY

“Quality of life” (QOL) measurement reflects the impact of a disease on the daily life of a patient, and this can be used as an outcome measure in clinical trials. QOL measurements are rarely used in patients with neuromuscular disease. The aim of this study was to determine whether QOL is reduced in chronic polyneuropathy, whether there is a relationship between QOL and objective measures of disease severity, and whether measuring QOL is a useful addition to the assessment of severity of polyneuropathy. We measured QOL in 90 patients with chronic axonal polyneuropathy (33 with hereditary motor and sensory neuropathy type II and 57 with chronic idiopathic axonal polyneuropathy) using the RAND 36‐item Health Survey questionnaire (RAND‐36). We compared the results with the QOL of a reference population, with summed motor and sensory scores, and with the Rankin scale for handicap. Patients had worse scores than the reference population on seven of eight areas of the RAND‐36. Patients with both low motor and low sensory scores rated lower in physical and emotional areas than less impaired patients. A low Rankin score was related only to physical domains. We conclude that in patients with chronic axonal polyneuropathy the severity of disease can be assessed with a general QOL instrument, and that this provides additional information, particularly on areas related to emotional and social functioning.