Treatment of Multiple Sclerosis With Teriflunomide. Multicenter Study of Real Clinical Practice in the Valencian Community-Spain

Introduction: We have different treatment alternatives for relapsing-remitting multiple sclerosis–RRMS–within the so-called platform drugs. It would be desirable to know the ideal drug for each patient. Real clinical practice studies provide us with data on drug efficacy in the medium and long term, safety beyond clinical trials, and can help us to know the patient profile appropriate for each therapy.Material and Methods: An observational multicenter study of real clinical practice in patients with RRMS who were treated with teriflunomide in the Valencian Community, since teriflunomide was authorized in Spain. The database created for this study collects retrospectively patients followed prospectively in the MS clinics.Objectives: To analyze the efficacy and safety of teriflunomide treatment in patients with RRMS under the conditions of real clinical practice, and to identify a patient profile responding to the treatment.Results: We obtained data from 340 patients who received at least one dose of 14 mg teriflunomide. The patients were 69.4% female to 30.6% male, had a mean age of 46.4 years, and a mean time of progression of MS of 11.5 years. The mean pre-teriflunomide relapse rate was 0.4 years, the mean EDSS scorewas 1.98, IgG Oligoclonal bands were present in the CSF of 66.2% of the patients, IgM Oligoclonal bands were present in 46.9%, and the mean number of gadolinium-enhancing lesions was 1.07 lesions per patient at the beginning of treatment. The average number of treatments previously received was 1.04, and 28.53% were naïve. After a follow-up of up to 4 years, a reduction in the annualized and cumulative annualized relapse rate was observed in the first year, in the second year, and in the third year, compared to the pre-treatment year. The EDSS scores were stabilized throughout the follow-up. Likewise, there was a reduction in gadolinium-enhancing lesions in the 1st and 2nd years compared to the pre-treatment period. Applying different generalized multiple linear regression models, we identified a profile of a responding patient to teriflunomide as a male without IgM oligoclonal bands in the CSF, a previous EDSS score of <3, and more than 5 years duration of MS.

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Clinical characteristics of multiple sclerosis in Taiwan: a cross-sectional study

Multiple Sclerosis Journal ◽

10.1191/1352458506ms1297oa ◽

2006 ◽

Vol 12 (4) ◽

pp. 501-506 ◽

Cited By ~ 31

Author(s):

K H Chang ◽

R K Lyu ◽

C M Chen ◽

W C Hsu ◽

Y R Wu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Total Protein ◽

Clinical Characteristics ◽

Age Of Onset ◽

Oligoclonal Bands ◽

First Year ◽

Annual Relapse Rate ◽

Igg Index ◽

The Mean

This study reviewed the clinical characteristics of multiple sclerosis (MS) in Taiwanese patients from 1993 to 2001. Of the 75 MS patients with a mean age of onset of 35.6±12.6 years, the female-to-male ratio was 4.4 (61/14). In 42 (56%) optico-spinal MS (OS-MS) patients, the age of onset (37.6±11.1 years) tended to be older than conventional MS (C-MS) patients (33.1±14.1 years, P = 0.08). In 60 cerebrospinal fluid (CSF) specimens, raised IgG index (>0.7) and oligoclonal bands were noted in 26 (43.3%) and two (3.3%) cases, respectively. The frequency of raised IgG index was lower in OSMS (31.3%) than in C-MS (57.1%, P = 0.07). The CSF total protein concentrations were significantly higher in OS-MS (64.5 mg/dL) than in C-MS (46.6 mg/dL, P = 0.047). The mean annual relapse rate was 54.1%, and was significantly higher within the first year (59.7%, P<0.001). The mean annual relapse rate in OS-MS (62.7%) was significantly higher than in C-MS (41.2%, P = 0.01). The differences in the annual relapse rate and total protein concentration in CSF between OS-MS and C-MS suggest probably two distinct immunopathogenesis. The higher first year relapse rate of MS patients in Taiwan may address the importance of early intervention with immunomodulatory therapy.

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Rheumatoid arthritis in real clinical practice. Results of the «Computer Terminals of Self-Assessment for Patients with Rheumatic Diseases» («TERMINAL-I») project

Modern Rheumatology Journal ◽

10.14412/1996-7012-2019-2-25-30 ◽

2019 ◽

Vol 13 (2) ◽

pp. 25-30 ◽

Cited By ~ 1

Author(s):

V. N. Amirdzhanova ◽

E. Yu. Pogozheva ◽

A. E. Karateev ◽

R. R. Samigullina ◽

O. B. Nesmeyanova ◽

...

Keyword(s):

Quality Of Life ◽

Rheumatoid Arthritis ◽

Clinical Practice ◽

Disease Activity ◽

Functional Status ◽

Disease Duration ◽

The Mean ◽

Real Clinical Practice

Objective: to describe the portrait of a patient with rheumatoid arthritis (RA) in real clinical practice, to assess disease activity from the point of view of a physician and a patient, functional status, quality of life (QOL), and the efficiency of the therapy performed.Patients and methods. The investigation enrolled 976 RA patients from a cohort of patients in the TERMINAL-I multicenter study, who, when visiting a rheumatologist, independently assessed the disease activity and QOL using a computer system (the «Computer Terminals of SelfAssessment for Patients with Rheumatic Diseases» project). The mean age of the patients was 52.30±13.3 years; women accounted for 85%; the median disease duration 8.0 [4.0; 14.0] years. Baseline clinical parameters and pharmacotherapy were evaluated for 6 months. The disease activity was determined by the DAS28 and RAPID-3 indices; functional status and quality of life were evaluated by the HAQ and the EQ-5D, respectively.Results. 83% of the RA patients were positive for rheumatoid factor and 60% were for anti-cyclic citrullinated peptide antibodies. There was a preponderance of patients with high (40.5%) and moderate (46.8%) RA activity; 6.9% were observed to have a low activity; 5.8% had clinical remission. The mean values of DAS28 and RAPID-3 were 4.7±1.3 and 13.7±3.6, respectively. Only 14.3% of patients had a good functional status that was comparable with the population-based control (HAQ≤0.5). The remaining patients were found to have a substantial decrease in joint functional parameters (median HAQ 1.88 [1.0; 2.5]) and EQ-5D QOL (0.60 [0.60; 0.74). Prosthetic joints were present in 7.4% of patients. At visit 1 to a rheumatologist, the therapy was changed in 15% of patients. During 6-month follow-up, conventional disease-modifying anti-rheumatic drugs were taken by almost all (91.2%) patients. Of them, 70.9% of the patients were treated with methotrexate (MTX): 77.0% received the latter at a dose of 15 mg/week and 23.0% had it at a dose of >15 mg (17.5 to 40 mg/week). Glucocorticoids could be stopped in 20.5% of the patients within six months. Tumor necrosis factor-α inhibitors and anti-B-cell therapy were used in 6.6 and 16.2% of patients, respectively. At 6-month follow-up (Visit 2), 54% of patients achieved a 20% clinical improvement in the ACR criteria. At the same time, the DAS28 scores decreased substantially from 4.5±1.2 to 3.8±1.1 (p = 0.0001). There was a minimal functional improvement in the HAQ index in 64% of patients and a better EQ-D QOL scores in 16%.Conclusion. The majority of RA patients who came to the rheumatologists showed high to moderate disease activity. This was due to long disease duration, inadequate MTX dose, and insufficient patient monitoring in real clinical practice. Introduction of a computer system for selfassessment of their health status by RA patients in an outpatient setting could improve the interaction of physicians, nurses, and patients, better monitor disease activity, and enhance therapeutic efficiency.

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The contribution of cerebrospinal fluid oligoclonal bands to the early diagnosis of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458508100502 ◽

2009 ◽

Vol 15 (4) ◽

pp. 472-478 ◽

Cited By ~ 27

Author(s):

V Zipoli ◽

B Hakiki ◽

E Portaccio ◽

F Lolli ◽

G Siracusa ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Clinical Practice ◽

High Risk ◽

Oligoclonal Bands ◽

Clinical Settings ◽

Current Clinical Practice ◽

Mcdonald Criteria ◽

Critical Issues

Background McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings. Objective To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice. Methods We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB). Results We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI. Conclusion OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.

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Determinants of therapeutic lag in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458520981300 ◽

2021 ◽

pp. 135245852098130

Author(s):

Izanne Roos ◽

Emmanuelle Leray ◽

Federico Frascoli ◽

Romain Casey ◽

J William L Brown ◽

...

Keyword(s):

Multiple Sclerosis ◽

Expanded Disability Status Scale ◽

Disability Progression ◽

Delayed Onset ◽

Disease Characteristics ◽

Disability Status ◽

Male Sex ◽

Pre Treatment ◽

Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

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Prospective study of multiple sclerosis with early onset

Multiple Sclerosis Journal ◽

10.1191/1352458502ms786oa ◽

2002 ◽

Vol 8 (2) ◽

pp. 115-118 ◽

Cited By ~ 93

Author(s):

A Ghezzi ◽

C Pozzilli ◽

M Liguori ◽

M G Marrosu ◽

N Milani ◽

...

Keyword(s):

Multiple Sclerosis ◽

First Year ◽

Hormonal Changes ◽

Disability Status ◽

Definite Multiple Sclerosis ◽

Relapsing Remitting ◽

Clinically Definite Multiple Sclerosis ◽

The Mean ◽

And Gender

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age ≥12 years, suggesting a role of hormonal changes in triggering MS onset. The mean follow-up duration was 10.9-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, > 6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset, age and gender.

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Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

Journal of Pediatric Neurology ◽

10.1055/s-0041-1736599 ◽

2021 ◽

Author(s):

Sandesh Kini ◽

Yellanthoor Ramesh Bhat ◽

Lakshmikanth Halegubbi Karegowda

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Case Report ◽

Demyelinating Disease ◽

Oligoclonal Bands ◽

Initial Manifestation ◽

Demyelinating Disorder ◽

The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

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Biologic Therapy in Refractory Non-Multiple Sclerosis Optic Neuritis Isolated or Associated to Immune-Mediated Inflammatory Diseases. A Multicenter Study

Journal of Clinical Medicine ◽

10.3390/jcm9082608 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2608

Author(s):

Alba Herrero-Morant ◽

Carmen Álvarez-Reguera ◽

José L. Martín-Varillas ◽

Vanesa Calvo-Río ◽

Alfonso Casado ◽

...

Keyword(s):

Multiple Sclerosis ◽

Optic Neuritis ◽

Multicenter Study ◽

Lupus Erythematosus ◽

Biologic Therapy ◽

Relapsing Polychondritis ◽

Immunosuppressive Drug ◽

Biologic Agent ◽

Open Label

We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 ± 13.9 years). The underlying diseases were Bechet’s disease (n = 5), neuromyelitis optica (n = 3), systemic lupus erythematosus (n = 2), sarcoidosis (n = 1), relapsing polychondritis (n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis (n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab (n = 6), rituximab (n = 6), infliximab (n = 5) and tocilizumab (n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate (n = 11), azathioprine (n = 2), mycophenolate mofetil (n = 1) and hydroxychloroquine (n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean ± SD BCVA (0.8 ± 0.3 LogMAR vs. 0.6 ± 0.3 LogMAR; p = 0.03), mean ± SD RNFL (190.5 ± 175.4 μm vs. 183.4 ± 139.5 μm; p = 0.02), mean ± SD MT (270.7 ± 23.2 μm vs. 369.6 ± 137.4 μm; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10–61.5) mg/day at baseline to. 2.5 (0–5) mg/day after one year of follow-up; p = 0.001. After a mean ± SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.

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Efficacy of rituximab in refractory neuromyelitis optica

Multiple Sclerosis Journal ◽

10.1177/1352458515602337 ◽

2015 ◽

Vol 22 (7) ◽

pp. 955-959 ◽

Cited By ~ 35

Author(s):

N Collongues ◽

D Brassat ◽

E Maillart ◽

P Labauge ◽

JC Ouallet ◽

...

Keyword(s):

Body Mass Index ◽

Maintenance Therapy ◽

Immunosuppressive Therapy ◽

Relapse Rate ◽

Neuromyelitis Optica ◽

Predictive Factor ◽

Population Based ◽

Annualized Relapse Rate ◽

The Mean

Background: Despite a growing use of rituximab (RTX) in neuromyelitis optica (NMO), data are lacking in patients with refractory NMO (RNMO), defined as cases with at least one relapse during immunosuppressive therapy. Objective: The purpose of this study was to assess RTX as a maintenance therapy in RNMO. Methods: Out of a total of 305 NMO cases from a population-based cohort, 21 RNMO patients received RTX during a mean follow-up period of 31 months. Results: After RTX, 11 patients (52.3%) were relapse free, meaning that 47.7% were refractory to RTX. The mean annualized relapse rate decreased from 1.3 to 0.4 ( p<0.001) and median EDSS from 5 to 3 ( p=0.02). Body mass index (BMI) was predictive of EDSS worsening. Conclusions: RTX is an effective and well-tolerated treatment in RNMO. BMI could be a predictive factor for efficacy.

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Resultats A Court Terme De La Trabeculoplastie Selective Au Laser Chez Les Patients Togolais

European Scientific Journal ESJ ◽

10.19044/esj.2017.v13n30p271 ◽

2017 ◽

Vol 13 (30) ◽

pp. 271

Author(s):

Dzidzinyo Kossi ◽

Djagnikpo Akouete ◽

Ayena Koffi Didier ◽

Vonor Kokou ◽

Maneh, Nidain ◽

...

Keyword(s):

Selective Laser Trabeculoplasty ◽

Treatment Results ◽

Short Term ◽

Laser Trabeculoplasty ◽

The Mean ◽

Laser Control ◽

Pre Treatment ◽

Primary Glaucoma ◽

Reduction Percentage

Aim: To check the short-term tonometric results of SLT in the treatment of primary glaucoma at the open angle and in charge of ocular hypertonias in Togolese people. Methods: A retrospective study was carried out in an ophthalmology center. The first 130 eyes of 72 patients benefited from the SLT laser procedure. The tonometric controls work object focus on follow-up at 1, 3, and 6 months post laser treatment. Results: 130 eyes of 72 patients were collected. The average age of the patients was 49.74 years (± 17.45) and the ages vary between 10 and 85 years. The average IOP of the laser before the laser (J0) was (24.99 ± 8.41) mm Hg. The mean IOP at the post-laser control at 1 month was (18.79 ± 3.73) mm Hg. The average IOP for the post-laser control at 3 months was (18.44 ± 3.81) mm Hg. The mean IOP at the post-laser control at 6 months was (18.13 ± 3.63) mm Hg. The percentage reduction in intraocular pressure compared to IOP was pretreated from 20.2% to 1 month; 22.1% at 3 months; and 23.3% at 6 months. In 1 month, 49.2% of the eyes we treated showed a reduction in IOP of less than 20% compared to IOP pretreatment. After 3 months and 6 months, it was 55.4% higher. Also, 52.3% have a PIO reduction percentage which is greater than or equal to 20% compared to pre-treatment IOP. Discussion: Selective laser trabeculoplasty, most especially, is interesting in ocular hypertonies. Treatment of over 180 ° allows one patient out of two to have a pressure reduction that is greater than or equal to 20%. Conclusion: The SLT presents a significant advantage for our glaucomatous patients.

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Lack of Prognostic Significance of Pre-Treatment Total Metabolic Tumor Volume (TMTV) in Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood-2018-99-113791 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1720-1720

Author(s):

Mayur Narkhede ◽

Sadaf Qureshi ◽

Maryam Yazdy ◽

Roxanna Juarez ◽

Giuseppe Esposito

Keyword(s):

Ct Scan ◽

B Cell ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Pet Ct ◽

The Mean ◽

Pre Treatment ◽

Pet Ct Scan ◽

Stage Stage

Abstract Background DLBCL is the most common non-Hodgkin lymphoma (NHL), making up about 30%-40% of NHL in the U.S. PET-CT is recommended as the most accurate imaging technique in DLBCL for staging and response assessment. Pretreatment assessment of PET-CT scan derived metrics such as TMTV has been shown to correlate with PFS and/or overall survival (OS) in DLBCL (Sasanelli 2014) We attempted to replicate this finding using EFS at 24 months as a primary endpoint and compare it with pre-treatment TMTV, TLG and cell of origin (COO). Methods 47 pts with newly diagnosed DLBCL and treated with R-CHOP at our institution between 2014 to 2018 were identified from our electronic medical record system for retrospective analysis after IRB approval. All pts had a pretreatment PET-CT scan available for TMTV measurement. All pts had a pretreatment biopsy which were reviewed along with their clinical information regarding treatment outcome and follow up. Patients were classified as to germinal center B cell (GCB) and non-GCB based on immunochemistry using the Hahn's algorithm. PET-CT scans were reviewed by two nuclear medicine physicians using synovia software, and measurements for TMTV and TLG were recorded. TMTV was calculated using a threshold of 41% of the max pixel value (based on prior studies) to draw the volume of interest (VOI) for a lesion. Pooled t-test was performed to compare TMTV, TLG and COO with EFS at 24 mos. Chi-Square test compared TMTV with COO Results Median age of pts was 58 years, with a median duration of follow up of 26 months. There were 33% with limited stage (Stage I or II) and 67% were advanced stage (Stage III or IV). The mean pretreatment TMTV and pretreatment TLG was 295cm3 and 4519 units. 49% were GCB subtype and 47 % non-GCB. Amongst all patients 19.2 % had an event within 24 mos. When TMTV was compared to EFS at 24 months the mean TMTV was 304 for those who had an event versus 294 without (p=0.95). TLG compared to EFS at 24 months showed a mean TLG of 3391 for those who had an event versus 4914 without (P=0.40). GCB and non-GCB had mean TMTV of 264 and 339 respectively with p =0.59. COO when compared to TLG had means of 4365 and 4933 for GCB and non-GBB respectively with p=0.79.Whereas there was no correlation between stage and COO (p=0.4296) TMTV correlated with Ann Arbor staging (p=0.0002). Conclusion This retrospective study failed to demonstrate a correlation between pre-treatment TMTV, TLG, COO and EFS at 24 months revealing the lack of prognostic significance of pretreatment PET scan derived metrics in DLBCL. Prior studies with TMTV did not evaluate EFS at 24 months as an endpoint and therefore, longer follow up might be needed to demonstrate prognostic significance of pretreatment TMTV minimizing it clinical significance. The different subtypes of DLBCL based on COO as assessed by Hahns algorithm also did not differ in their disease burden as measured by TMTV. Disclosures No relevant conflicts of interest to declare.

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