Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

Relationship between Homocysteine and Muscle Strength Decline: The Baltimore Longitudinal Study of Aging.

Background: Decreased muscle strength is strongly associated with future mobility limitations in older adults. Homocysteine is a risk factor for vascular disease and may exacerbate muscle strength decline. The present study aimed to examine the association between homocysteine levels and muscle strength in adults aged 50 years or older. Methods: Data were from 1,101 participants of The Baltimore Longitudinal Study of Aging between December 2004 and March 2015. Muscle strength was measured using grip strength. Mixed effects linear regression was used to estimate the association between homocysteine and muscle strength in men and women, separately. Results: Total mean follow-up time was 4.7 ± 3.1 years, range from 0 to 10.1 years. Baseline mean grip strength was 39.9 kg for men and 25.5 kg for women. Grip strength declined over the follow-up time for both men and women. Among women, there was a significant inverse relationship between homocysteine and grip strength, where grip strength declined as a function of increasing homocysteine over time (ß = -0.05, p = .031). Among men, an increase of 1 µmol/L in homocysteine was associated with -0.10 kg decrease in grip strength, though not significantly. Conclusions: In this study of healthy older adults aged 50 years or older, higher homocysteine was related to lower muscle strength in women. This is the first study to characterize the relationship over a long follow-up period. Future research should focus on assessing homocysteine as a marker of physical function decline and translating the relationship into clinical and public health practice.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

BACKGROUND: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. METHODS: The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. RESULTS: The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. CONCLUSIONS: The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.

Autonomic and electrocardiographic findings in Parkinson's disease.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P<0.05) between QTcB and PD severity in individuals that were taking QT-interval affecting drugs. A longer QT-interval at baseline was associated with more advanced PD at 5years (P<0.05), and greater disease progression over 5years (P<0.05). There was an association between diminished HRV and an orthostatic decrease in standing blood pressure at baseline in individuals with PD (P<0.05). HRV was not associated with PD severity or progression. In conclusion, we were able to detect measurable associations between the QTcB interval and PD severity, PD severity 5years later, and the change in disease over time. However, routine ECG tracings appear inadequate for the evaluation of autonomic function in PD.

Regular Exercise, Quality of Life, and Mobility in Parkinson's Disease: A Longitudinal Analysis of National Parkinson Foundation Quality Improvement Initiative Data.

BACKGROUND: Research-based exercise interventions improve health-related quality of life (HRQL) and mobility in people with Parkinson's disease (PD). OBJECTIVE: To examine whether exercise habits were associated with changes in HRQL and mobility over two years. METHODS: We identified a cohort of National Parkinson Foundation Quality Improvement Initiative (NPF-QII) participants with three visits. HRQL and mobility were measured with the Parkinson's Disease Questionnaire (PDQ-39) and Timed Up and Go (TUG). We compared self-reported regular exercisers (≥2.5 hours/week) with people who did not exercise 2.5 hours/week. Then we quantified changes in HRQL and mobility associated with 30-minute increases in exercise, across PD severity, using mixed effects regression models. RESULTS: Participants with three observational study visits (n = 3408) were younger, with milder PD, than participants with fewer visits. After 2 years, consistent exercisers and people who started to exercise regularly after their baseline visit had smaller declines in HRQL and mobility than non-exercisers (p < 0.05). Non-exercisers worsened by 1.37 points on the PDQ-39 and a 0.47 seconds on the TUG per year. Increasing exercise by 30 minutes/week was associated with slower declines in HRQL (-0.16 points) and mobility (-0.04 sec). The benefit of exercise on HRQL was greater in advanced PD (-0.41 points) than mild PD (-0.14 points; p < 0.02). CONCLUSIONS: Consistently exercising and starting regular exercise after baseline were associated with small but significant positive effects on HRQL and mobility changes over two years. The greater association of exercise with HRQL in advanced PD supports improving encouragement and facilitation of exercise in advanced PD.

Predictors of intensive care unit length of stay and intracranial pressure in severe traumatic brain injury.

OBJECTIVE: The aim of this study was to explore the relationship of intracranial pressure (ICP) with intensive care unit (ICU) length of stay in a large cohort of severe traumatic brain injury patients and identify factors associating with prolonged ICU course. METHODS: This was a single-center database review of de-identified research data that had been prospectively collected; setting: neurosurgical ICU, Ben Taub General Hospital, Houston, TX. RESULTS: In a cohort of 438 severe traumatic brain injury (TBI) patients, 149 (34%) had a motor Glasgow Coma Scale score of 1 to 3 on admission and 284 (65%) had 4 to 5. Intracranial pressure during the ICU course was 19.8±11.2 mm Hg. Favorable outcome was obtained in 148 (34%), and unfavorable, in 211 (48%) patients with a mortality of 28%. ICU length of stay (LOS) was 19.4±13.9 days. Joint modeling of ICP and ICU LOS was undertaken, adjusted for the International Mission for Prognosis and Analysis of Clinical Trials in TBI admission prognostic indicators. A higher ICP was not significantly associated with longer ICU LOS (P=.4). However, presence of a mass lesion on admission head computed tomography was strongly correlated with a prolonged ICU LOS (P=.0007). Diffuse injuries with basal cistern compression or midline shift were marginally associated with a longer ICU LOS (P=.053). CONCLUSIONS: ICP, as monitored and managed according to BTF guidelines, is not associated with ICU length of stay. Patients with severe TBI and a mass lesion on admission head computed tomography were found to have prolonged ICU LOS independently of other indicators of injury severity and intracranial pressure course.

Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00449865.

Rankin scale as a potential measure of global disability in early Parkinson's disease.

We conducted an exploratory analysis of the utility of the modified Rankin Scale (mRS) as a global measure of disability in early Parkinson's diesase (PD) using the baseline data from a large cohort of PD patients enrolled in a longitudinal study of creatine. The mRS is scored 0-6 with lower scores reflecting less disability. For the analysis the mRS score was dichotomized at <2 versus ≥2. We explored the association of the mRS with multiple measures of PD-related impairments, including the Unified Parkinson Disease Rating Scale (UPDRS); cognitive function characterized by the Symbol Digit Modalities--verbal, and Scales for Outcomes in Parkinson's disease--cognition (SCOPA-COG); quality of life (Parkinson's disease questionnaire [PDQ-39]) and EuroQOL; Beck Depression Inventory II (BDI); and Total Functional Capacity (TFC). We also investigated the interaction between variables. One thousand seven hundred forty-one patients were included in the analysis of which 374 had a mRS score of 2 or above. In the univariate model, all interested measures except SCOPA-COG (p=0.23) had significant association with mRS (p<0.001) after controlling for confounders. In the multivariate model, UPDRS Part II and III (activities of daily living and motor), BDI, TFC and PDQ-39 were significant (p<0.05). The mRS has a significant association with the wide spectrum of measures of impairment and quality of life in early PD and shows good potential to be a global measure of disability in early PD. The sensitivity of the mRS to change and performance of the scale in more advanced PD will have to be established longitudinally.