Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

<p>Abstract</p> <p>Background</p> <p>High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-Tooth type 1A patients and whether this treatment is safe.</p> <p>Methods</p> <p>Patients below age 25 years were randomly assigned to receive placebo or ascorbic acid (one gram twice daily) in a double-blind fashion during one year. The primary outcome measure was the change over time in motor nerve conduction velocity of the median nerve. Secondary outcome measures included changes in minimal F response latencies, compound muscle action potential amplitude, muscle strength, sensory function, Charcot-Marie-Tooth neuropathy score, and disability.</p> <p>Results</p> <p>There were no significant differences between the six placebo-treated (median age 16 years, range 13 to 24) and the five ascorbic acid-treated (19, 14 to 24) patients in change in motor nerve conduction velocity of the median nerve (mean difference ascorbic acid as opposed to placebo treatment of 1.3 m/s, confidence interval -0.3 to 3.0 m/s, <it>P </it>= 0.11) or in change of any of the secondary outcome measures over time. One patient in the ascorbic acid group developed a skin rash, which led to discontinuation of the study medication.</p> <p>Conclusion</p> <p>Oral high dose ascorbic acid for one year did not improve myelination of the median nerve in young Charcot-Marie-Tooth type 1A patients. Treatment was relatively safe.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635.</p

Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol

Contains fulltext : 96704.pdf (publisher's version ) (Open Access)BACKGROUND: Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated. METHODS/DESIGN: The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI. DISCUSSION: The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from "normal" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism

Validation of a Model Predicting De Novo Stress Urinary Incontinence in Women Undergoing Pelvic Organ Prolapse Surgery

OBJECTIVE: To validate a previously developed prediction model for de novo stress urinary incontinence (SUI) after undergoing vaginal surgery for pelvic organ prolapse (POP). METHODS: Model performance was determined using a cohort of women who participated in two, 14-center randomized trials in the Netherlands that evaluated whether postoperative SUI 1 year after surgery was reduced with or without concomitant midurethral sling at the time of surgery for symptomatic women who had at least stage 2 POP. Age, number of previous vaginal births, urine leakage associated with urgency, history of diabetes, body mass index, preoperative stress test result, and placement of a midurethral sling were used to calculate the predicted probability of an individual developing de novo SUI. Predicted probabilities were compared with outcomes and quantitated using the concordance index and calibration curves. Model accuracy was compared with and without the preoperative stress test, and net reclassification improvement was measured using probability cutoffs of 0.2, 0.3, and 0.4. RESULTS: Of 239 participants who did not report preoperative SUI and underwent surgery, 152 were eligible for analysis with complete baseline and outcome data. Model discrimination was acceptable and consistent with performance in the original development cohort when the preoperative stress test result was included (concordance index 0.63; 95% CI 0.52-0.74) and had lower discrimination than when the stress test variable was not included (concordance index 0.57; 95% CI 0.46-0.67, P=.048). The model that included the stress test variable was most accurate when predicted probabilities of de novo SUI were between 0 and 50%, and it correctly reclassified upward 5.9% (95% CI -14.8 to 26.8) of participants with de novo SUI and correctly reclassified downward 16.9% (95% CI 6.6-27.7) of participants without de novo SUI. CONCLUSION: On external validation, the model was predictive of de novo SUI after vaginal prolapse surgery and may facilitate decision making regarding concomitant sling placement. CLINICAL TRIAL REGISTRATION: Nederlands Trial Register, NTRR 1197 en 1070