Reliability and equivalence of alternate forms for the Symbol Digit Modalities Test: implications for multiple sclerosis clinical trials

2012 ◽  
Vol 18 (9) ◽  
pp. 1320-1325 ◽  
Author(s):  
Ralph HB Benedict ◽  
Audrey Smerbeck ◽  
Rajavi Parikh ◽  
Jonathan Rodgers ◽  
Diego Cadavid ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Statistical Tests ◽  
Standard Form ◽  
Latin Square ◽  
Brain Magnetic Resonance Imaging ◽  
Good Evidence ◽  
Order Effects ◽  
Mean Values ◽  
Alternate Forms

Background: Cognitive impairment is common in multiple sclerosis (MS), but is seldom assessed in clinical trials investigating the effects of disease-modifying therapies. The Symbol Digit Modalities Test (SDMT) is a particularly promising tool due to its sensitivity and robust correlation with brain magnetic resonance imaging (MRI) and vocational disability. Unfortunately, there are no validated alternate SDMT forms, which are needed to mitigate practice effects. Objective: The aim of the study was to assess the reliability and equivalence of SDMT alternate forms. Methods: Twenty-five healthy participants completed each of five alternate versions of the SDMT – the standard form, two versions from the Rao Brief Repeatable Battery, and two forms specifically designed for this study. Order effects were controlled using a Latin-square research design. Results: All five versions of the SDMT produced mean values within 3 raw score points of one another. Three forms were very consistent, and not different by conservative statistical tests. The SDMT test–retest reliability using these forms was good to excellent, with all r values exceeding 0.80. Conclusions: For the first time, we find good evidence that at least three alternate versions of the SDMT are of equivalent difficulty in healthy adults. The forms are reliable, and can be implemented in clinical trials emphasizing cognitive outcomes.

Liraglutide for the Treatment of Obesity: Analyzing Published Reviews

2019 ◽  
Vol 25 (15) ◽  
pp. 1783-1790 ◽  
Author(s):  
Rosario Pastor ◽  
Josep A. Tur
Keyword(s):  
Weight Loss ◽  
Clinical Trials ◽  
Systematic Reviews ◽  
Randomized Clinical Trials ◽  
Statistical Tests ◽  
Overweight And Obesity ◽  
Cochrane Library ◽  
Medical Subject Headings ◽  
Mesh Terms ◽  
Treatment Of Obesity

Background: Several drugs have been currently approved for the treatment of obesity. The pharmacokinetic of liraglutide, as well as the treatment of type 2 diabetes mellitus, have been widely described. Objective: To analyze the published systematic reviews on the use of liraglutide for the treatment of obesity. Methods: Systematic reviews were found out through MEDLINE searches, through EBSCO host and the Cochrane Library based on the following terms: "liraglutide" as major term and using the following Medical Subject Headings (MesH) terms: "obesity", "overweight", "weight loss". A total of 3 systematic reviews were finally included to be analyzed. Results: From the three systematic reviews selected, only two included the randomized clinical trials, while the third study reviewed both randomized and non-randomized clinical trials. Only one review performed statistical tests of heterogeneity and a meta-analysis, combining the results of individual studies. Another review showed the results of individual studies with odds ratio and confidence interval, but a second one just showed the means and confidence intervals. In all studies, weight loss was registered in persons treated with liraglutide in a dose dependent form, reaching a plateau at 3.0 mg dose, which was reached just in men. Most usual adverse events were gastrointestinal. Conclusion: More powerful and prospective studies are needed to assess all aspects related to liraglutide in the overweight and obesity treatment.

Digital Technology in Clinical Trials for Multiple Sclerosis: a systematic review. (Preprint)

2020 ◽  
Author(s):  
Marcello De Angelis ◽  
Luigi Lavorgna ◽  
Antonio Carotenuto ◽  
Martina Petruzzo ◽  
Roberta Lanzillo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Outcome Measures ◽  
Digital Technology ◽  
Clinical Trial Design ◽  
Motor Rehabilitation ◽  
Robot Assisted ◽  
Future Directions ◽  
Treatment Side Effects

BACKGROUND Clinical trials in multiple sclerosis (MS) have leveraged the use of digital technology to overcome limitations in treatment and disease monitoring. OBJECTIVE To review the use of digital technology in concluded and ongoing MS clinical trials. METHODS In March 2020, we searched for “multiple sclerosis” and “trial” on pubmed.gov and clinicaltrials.gov using “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Overall, we included thirty-five studies. RESULTS Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Also, digital technology has become increasingly used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms. Some trials have been developing new patient-centred outcome measures for the detection of symptoms and of treatment side effects and adherence. CONCLUSIONS We will discuss how digital technology has been changing MS clinical trial design, and possible future directions for MS and neurology research.

scholarly journals Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Therapeutic Benefit ◽  
Disease Modifying Therapies ◽  
Long Term Follow Up ◽  
Post Hoc ◽  
Switch Group ◽  
Relevant Outcome

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.

scholarly journals Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Stephen D. Silberstein ◽  
Joshua M. Cohen ◽  
Ronghua Yang ◽  
Sanjay K. Gandhi ◽  
Evelyn Du ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Medication Use ◽  
Two Phase ◽  
Double Blind ◽  
Treatment Benefit ◽  
Mean Values ◽  
Treatment Benefits ◽  
Acute Headache ◽  
Post Hoc ◽  
Insight Into

Abstract Background Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials? Methods We included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL). Results Overall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations. Conclusions Fremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice. Trial registration ClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

scholarly journals The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): Validation in Arabic and Lebanese Normative Values

2021 ◽  
pp. 1-10
Author(s):  
Hala Darwish ◽  
Pia Zeinoun ◽  
Natali Farran ◽  
Husam Ghusn ◽  
Bassem Yamout ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Psychometric Properties ◽  
Cognitive Assessment ◽  
Healthy Subjects ◽  
Good Evidence ◽  
Normative Values ◽  
Arabic Version ◽  
Retest Reliability ◽  
Test Retest Reliability ◽  
Healthy Participants

Abstract Objective: Multiple sclerosis (MS) is often associated with cognitive deficits. Accurate evaluation of the MS patients’ cognitive performance is essential for diagnosis and treatment recommendation. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS), widely used cognitive testing battery, examines processing speed, verbal and visuospatial learning, and memory. Our study aims to examine the psychometric properties of an Arabic version of the BICAMS and to provide normative values in a Lebanese sample. Method: The BICAMS, comprised of the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and a newly developed verbal learning/memory test, the Verbal Memory Arabic Test (VMAT), were administered on healthy subjects and MS patients. The sample consisted of 180 healthy individuals, of whom 63 were retested after 2–3 weeks. Forty-three MS patients matched with 43 healthy subjects based on age, sex, and years of education were assessed. A sample of 10 MS patients was also examined on two occasions. Test–retest reliability and criterion-related validity were examined, and regression-based norms were derived. Results: The test–retest correlations showed good evidence of reliability with coefficients ranging between 0.64 and 0.73 in the healthy sample, and between 0.43 and 0.92 in the MS sample. The BICAMS was able to discriminate between MS patients and matched healthy participants on the SDMT and BVMT-R. Normative data were comparable to other studies. Conclusions: This new Arabic version of the BICAMS shows initial good psychometric properties. While good evidence of VMAT’s reliability was shown in the healthy participants, less test–retest reliability in this tool was seen in the MS group, and partial criterion-related validity was evident. This renders further examination of the VMAT. We provide regression-based norms for a Lebanese sample and encourage the use of this battery in both research and clinical settings.

Multiple sclerosis and HLA genotypes: A possible influence on brain atrophy

2017 ◽  
Vol 25 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Lorena Lorefice ◽  
Giuseppe Fenu ◽  
Claudia Sardu ◽  
Jessica Frau ◽  
Giancarlo Coghe ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
High Risk ◽  
Brain Atrophy ◽  
Group Versus ◽  
Brain Magnetic Resonance Imaging ◽  
Human Leukocyte ◽  
Low Risk ◽  
Brain Volume Loss ◽  
Hla Genotypes ◽  
Hla Genotype

Background: The strongest genetic determinant for multiple sclerosis (MS) is located at the human leukocyte antigen (HLA) class II DRB1 and DQB1 loci. Objectives: To investigate the possible role of predisposing HLA genotypes in determining brain atrophy. Methods: HLA genotypes were categorized as high risk (two predisposing haplotypes) or medium/low risk (one or no predisposing haplotypes). Patients underwent a brain magnetic resonance imaging (MRI) study and volumes of white matter (WM), gray matter (GM), and whole brain (WB) were estimated with SIENAX. Longitudinal atrophy was also assessed with SIENA. Results: The study included 240 MS patients. In 51/240 (21%) subjects, a high-risk HLA genotype was observed, while medium- and low-risk HLA genotypes were 109/240 (45%) and 80/240 (34%), respectively. Multiple regression analysis found that the high-risk HLA genotype was associated with significant reduction in WB ( p = 0.02) and GM ( p = 0.03) volumes compared with the medium-/low-risk HLA genotypes, independently from MS clinical features. The longitudinal study included 60 patients and showed a brain volume loss of −0.79% in high-risk HLA genotype group versus −0.56% in low-risk HLA genotype. Conclusion: Our results suggest an influence of HLA genotype on WB and GM atrophy. Further investigations are necessary to confirm these findings.

Oral contraceptives and psychological symptoms

1969 ◽  
Vol 7 (1) ◽  
pp. 2-4
Keyword(s):  
Clinical Trials ◽  
Oral Contraceptives ◽  
Psychological Symptoms ◽  
Good Evidence ◽  
Reliable Data ◽  
Intermediary Metabolism ◽  
Control Groups ◽  
Cerebral Activity ◽  
The Brain

Psychological symptoms are notoriously difficult to assess, and it is not surprising that the reported incidence of such symptoms in women taking oral contraceptives varies widely. The apparent incidence may further be influenced by what the subjects think they are expected to say. Clinical trials of oral contraceptives where psychological symptoms have been specifically studied provide the most reliable data, but control groups have so far been examined in only a few trials. Data on such symptoms from trials where unwanted effects were merely noted in passing are unreliable. There is however good evidence that synthetic progestagens influence cerebral activity1–3 and intermediary metabolism in the brain4 in both women and animals and that these effects do not mimic those of pregnancy.

De novo convulsive status epilepticus in patients with multiple sclerosis treated with dalfampridine

2018 ◽  
Vol 25 (4) ◽  
pp. 618-621 ◽  
Author(s):  
Emilie Panicucci ◽  
Mikael Cohen ◽  
Veronique Bourg ◽  
Fanny Rocher ◽  
Pierre Thomas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Status Epilepticus ◽  
De Novo ◽  
Case Reports ◽  
Brain Magnetic Resonance Imaging ◽  
Convulsive Status Epilepticus ◽  
Biological Tests ◽  
History Of ◽  
Magnetic Resonance Imaging Mri ◽  
History Of Epilepsy

Background: Dalfampridine extended release (DAL) is a broad-spectrum voltage-gated potassium channel blocker that is indicated in multiple sclerosis to improve the nerve conduction of demyelinated axons. Seizures are a known side effect of DAL, which is contraindicated in patients with a history of epilepsy. Objective: Three cases of multiple sclerosis (MS) with de novo convulsive status epilepticus (CSE) probably related to dalfampridine administration are described. Methods: No patients had a history of seizures or renal impairment. Biological tests were normal. A brain magnetic resonance imaging (MRI) showed diffuse cortical and subcortical atrophy without active inflammatory lesions. Results: All three patients presented with CSE that was attributed to DAL and so was discontinued. Conclusion: These case reports illustrate that, aside from seizures, de novo CSE is a potential complication of MS patients treated with DAL.

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