Source code and simulation data for the prediction of the electrodeposition mechanism of nanostructured metallic coatings.

This data article presents a simulation model based on quantum mechanics and energy potentials for obtaining simulation data that allows, from the perspective of materials informatics, the prediction of the electrodeposition mechanism for forming nanostructured metallic coatings. The development of the research is divided into two parts i) the formulation (Quantum mechanical model and Corrected model for electron prediction; using a modified Schrödinger equation) and ii) the implementation of the theoretical prediction model (Discretization of the model). For the simulation process, the finite element method (FEM) was used considering the equation of electric potential and electroneutrality with and without the inclusion of quantum leap. We also provide the code to perform QM simulations in CUDA®, and COMSOL® software, the simulation parameters, and data for two metallic arrangements of chromium nanoparticles (CrNPs) electrodeposited on commercial steel substrate. (CrNPs-AISI 1020 steel and CrNPs-A618 steel). Data collection shows the direct relationship between applied potential (VDC), current (A), concentration (ppm), and time (s) for the homogeneous formation of the coating during the electrodeposition process, as estimated by the theoretical model developed. Their potential reuse data is done to establish the precision of the theoretical model in predicting the formation and growth of nanostructured surface coatings with metallic nanoparticles to give surface-mechanical properties.

Cost-utility of oral methylprednisolone in the treatment of multiple sclerosis relapses: Results from the COPOUSEP trial.

BACKGROUND: Studies have shown that oral high-dose methylprednisolone (MP) is non-inferior to intravenous MP in treating multiple sclerosis relapses in terms of effectiveness and tolerance. In order to assist with resource allocation and decision-making, its cost-effectiveness must also be assessed. Our objective was to evaluate the cost-utility of per os high-dose MP as well as the cost-savings associated with implementing the strategy. METHODS: A cost-utility analysis at 28 days was carried out using data from the French COPOUSEP multicenter, double-blind randomized controlled non-inferiority trial and the statutory health insurance reimbursement database. Costs were calculated using a societal perspective, including both direct and indirect costs. An incremental cost-effectiveness ratio was calculated and bootstrapping methods assessed the uncertainty surrounding the results. An alternative scenario analysis in which MP was administered at home was also carried out. A budgetary impact analysis was carried at five years. RESULTS: In the conditions of the trial (hospitalized patients), there was no significant difference in utilities and costs at 28 days. The incremental cost-effectiveness ratio was €15,360 per quality-adjusted life-year gained. If multiple sclerosis relapses were treated at home, oral MP would be more effective, less costly and associated with annual savings up to 25 million euros for the French healthcare system. CONCLUSIONS: Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders.

BACKGROUND: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). OBJECTIVE: To characterize a cohort of MS patients with atypical myelitis. METHODS: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. RESULTS: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3-6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. CONCLUSION: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

Immunization and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society.

OBJECTIVES: To establish recommendations on immunization for patients with multiple sclerosis (MS). BACKGROUND: Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients. METHODS: The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975-June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain. RESULTS: Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs. CONCLUSION: Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.

Digestive side-effects with teriflunomide: Thoughts on lactose.

INTRODUCTION: Teriflunomide, a novel, orally bioavailable, active metabolite of leflunomide, has anti-inflammatory activity. It is prescribed as a first-line treatment for relapsing-remitting multiple sclerosis (RRMS) at a dose of one 14mg tablet per day. Common adverse reactions observed in placebo-controlled trials with a frequency≥10% and a rate twofold or more than reported with placebo, include digestive disorders. As teriflunomide tablets also contain lactose, the official recommendations are clear about not prescribing this drug to patients with known lactose intolerance and those with rare hereditary problems due to galactose intolerance. METHODS: Our study systematically collected, from our MS clinical practice, all adverse events presenting in the first 100 patients treated with teriflunomide. All of these patients were systematically asked if they were known to have lactose intolerance. RESULTS: None of these 100 patients declared having known, documented lactose intolerance. Yet, after starting teriflunomide, 14 reported mild-to-moderate diarrhea, which resolved within a month, but four of these patients continued to have daily diarrhea (grade 2 WHO classification), prompting us to perform a lactose breath test (LBT) for malabsorption. All four tested positive and were therefore diagnosed with lactose intolerance. Digestive symptoms were resolved with probiotics, and teriflunomide was maintained in three cases; the fourth patient decided, despite the adverse event being resolved, to stop taking teriflunomide. CONCLUSION: In cases of prolonged digestive side-effects after the introduction of teriflunomide, a lactose-malabsorption breath test should be proposed to confirm the culpability or not of an enzymatic defect in the occurrence of adverse events.

Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients.

BACKGROUND: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. METHODS: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. RESULTS: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). CONCLUSION: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.

Rhythmic abilities and musical training in Parkinson's disease: do they help?

Rhythmic auditory cues can immediately improve gait in Parkinson's disease. However, this effect varies considerably across patients. The factors associated with this individual variability are not known to date. Patients' rhythmic abilities and musicality (e.g., perceptual and singing abilities, emotional response to music, and musical training) may foster a positive response to rhythmic cues. To examine this hypothesis, we measured gait at baseline and with rhythmic cues in 39 non-demented patients with Parkinson's disease and 39 matched healthy controls. Cognition, rhythmic abilities and general musicality were assessed. A response to cueing was qualified as positive when the stimulation led to a clinically meaningful increase in gait speed. We observed that patients with positive response to cueing (n = 17) were more musically trained, aligned more often their steps to the rhythmic cues while walking, and showed better music perception as well as poorer cognitive flexibility than patients with non-positive response (n = 22). Gait performance with rhythmic cues worsened in six patients. We concluded that rhythmic and musical skills, which can be modulated by musical training, may increase beneficial effects of rhythmic auditory cueing in Parkinson's disease. Screening patients in terms of musical/rhythmic abilities and musical training may allow teasing apart patients who are likely to benefit from cueing from those who may worsen their performance due to the stimulation.

Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1.

BACKGROUND: Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project. METHODS: The ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mAb to compete with patients' IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site-directed mutagenesis, and hydrogen/deuterium exchange-mass spectrometry. RESULTS: The 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping with the binding sites of patients' serum IgEs. Mutation of residues P59, E60, and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44-K55 and R70-F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mAbs interact with >90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross-reactivity with other allergens of the PR-10 family. CONCLUSIONS: MAbs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1-specific quantitative ELISA adopted by the European Pharmacopoeia.

Monitoring CD27+ memory B-cells in neuromyelitis optica spectrum disorders patients treated with rituximab: Results from a bicentric study.

BACKGROUND: Rituximab (RTX) is increasingly used in the treatment of neuromyelitis optica spectrum disorder (NMO-SD). Administration regimen is not consensual as there is no reliable biomarker of RTX efficacy. In most cases, after induction, RTX is administered systematically every 6months. OBJECTIVE: To assess efficacy and safety of a maintenance regimen based on CD19+ CD27+ memory B-cell (mBc) detection. METHODS: We conducted a study in two French centers, including patients with NMO-SD who received an induction therapy with RTX. We compared the number of administered infusions, relapses and EDSS depending on two maintenance schemes (S1: administration of 1g RTX infusion every 6months or S2: a scheme based on regular mBc detection. 1g RTX was administered if mBc was >0.05%) RESULTS: 40 patients were included (mean age: 40.2years, F/M sex ratio: 5/1). Aquaporin-4 antibodies were positive in 75% patients. Under S1 regimen, all patients received 2 infusions per year, whereas under S2, they received 1.62 infusion per year. The mean interval between infusions under S2 was 7.4months, without decrease of clinical efficacy. CONCLUSION: In our study, mBc-based administration of RTX allowed personalizing treatment administration and in several cases to lower the cumulative dose without loss of efficacy.

[Internal fixation of the distal radius: Medical liability considerations]. / Ostéosynthèses de l'extrémité distale du radius : aspects médico-légaux.

Fixation of distal radius fractures is now the primary surgical procedure leading to medical liability claims for surgeons dealing with injuries to the upper limb. The main reasons for incrimination are complex regional pain syndrome and an unfavorable progression toward malunion. Infectious problems are relatively rare and, in general, well controlled. The associated capsule and ligament damage can be underestimated at the time of the initial assessment, which points to the need for complementary imaging in case of doubt. The prevention of claims inevitably requires a judicious choice of the fixation technique, which is adapted to the anatomical fracture type and to the patient. The best defense is a complete medical record, with emphasis on traceable information.

Evaluation of quality of life and fatigue in radiologically isolated syndrome.

BACKGROUND: Radiologically isolated syndrome (RIS) is a new subtype entity described at the very left of the demyelinating disease spectrum, where spatial dissemination of T2-weighted lesions can be documented on MRI in subjects with no history of neurological symptoms. OBJECTIVES: This study was a longitudinal assessment of health-related quality of life (HRQOL) and fatigue in RIS patients. METHODS: Non-converted RIS patients were evaluated at the time of diagnosis, and at 1 and 2 years of follow-up; their scores were compared with scores in clinically isolated syndrome (CIS) patients and age-matched controls. RESULTS: Sociodemographic characteristics were comparable at baseline. There was no statistical difference between RIS and CIS groups in terms of cerebrospinal fluid (CSF) positivity or T2 lesion load. For HRQOL evaluations, RIS patients scored the same as controls, while CIS patients scored lower. Fatigue was detectable in both RIS and CIS patients compared with baseline and with controls. Mental HRQOL scores decreased significantly for RIS patients during follow-up. CONCLUSION: HRQOL impairment and fatigue were detectable during follow-up in both non-converted RIS and CIS patients.

Should a psychotic or manic episode be considered an early manifestation of Multiple Sclerosis? A multiple case study.

BACKGROUND: Early manifestations of Multiple Sclerosis (MS) can be atypical and misleading, and several case report studies have highlighted that MS onset sometimes takes the form of a psychotic or manic episode. METHODS: All neurologists belonging to the French Multiple Sclerosis Observatory network were contacted by email and were asked to find patients with MS who presented with a history of psychiatric episode(s) near MS onset. RESULTS: Seventeen patients were selected that met the criteria of presenting with psychotic or manic symptoms either before the diagnosis of MS (N=8), or at the time of the first neurological episode or shortly after (N=9). Patients with a history of a psychiatric episode occurring before the first neurological episode were diagnosed on average 7 years later than patients with either a first neurological or a mixed (both neurological and psychiatric) episode. However, psychiatric symptoms in the first group and the first neurological symptoms of MS in the second group occurred at a similar age. CONCLUSION: Based on this multiple case study, we question whether past psychotic or manic episode should be considered equivalent to a first manifestation of MS.

The radiologically isolated syndrome.

Even prior to the introduction of criteria defining the radiologically isolated syndrome (RIS), longitudinal clinical data from individuals with incidentally identified T2 lesions suggestive of multiple sclerosis (MS) were described. Healthy individuals who do not exhibit signs of neurological dysfunction may have a brain MRI performed for a reason other than suspicion of MS that reveals unexpected anomalies highly suggestive of demyelinating plaques given their size, location, and morphology. These healthy subjects lack a history or symptomatology suggestive of MS and fulfill formal criteria for RIS, a recently described MS subtype that shares the phenotype of at-risk individuals for future demyelinating events. A formal description of RIS was first introduced in 2009 by Okuda et al., and defines a cohort of individuals who are at risk for future demyelinating events. European or North American observational studies have found that up to 30-45% of patients presenting with RIS will present with neurological symptoms, either acute or progressive. The median time to clinical conversion differs between studies. It was 2.3 years for a series of French patients and 5.4 years for an American cohort. Most patients who developed clinical symptoms had prior radiological progression. The presence of asymptomatic lesions in the cervical cord indicated an increased risk of progression, either to relapsing or to progressive MS. The consortium studying the epidemiology of RIS worldwide (RISC) presented their first retrospective cohort last year. Data were available for 451 RIS subjects (F: 354 [78.5%]). The mean age at RIS diagnosis was 37.2 years with a mean clinical follow-up time of 4.4 years. The observed 5-year conversion rate to the first clinical event was 34%. Of the converters within this time period, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age, sex (male), and lesions within the cervical or thoracic spinal cord were identified as significant predictors for the development of a first clinical event. Cognitive impairment is observed in RIS patients, and two studies demonstrated a significant proportion of patients with cognitive decline compared with healthy controls. Despite progress into the characterization of RIS subjects and into our understanding of risk factors for initial symptom development, the natural course of such cases and risk-profiles for a seminal neurological event, from prospectively acquired data, remain unclear. A prospective study is mandatory to increase our knowledge about these asymptomatic patients and individual therapeutic initiatives cannot be undertaken until a prospective clinical study demonstrates the benefit of introducing a disease modifying treatment for this very early stage of a chronic demyelinating disease.

Tear analysis as a tool to detect oligoclonal bands in radiologically isolated syndrome.

BACKGROUND: Although radiologically isolated syndrome (RIS) is a newly defined entity, incidental findings of T2 hypersignals on brain MRI can lead to misdiagnosis or useless investigations. The detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a major indicator that helps in diagnosis of subclinical inflammatory disease of the central nervous system, but lumbar puncture still remains an invasive option. METHODS: We have prospectively included patients with RIS, have compared the results of CSF and tear OCB detection by isoelectric focusing (IEF) and assessed concordance between OCB detection in tears and in CSF. Tears were collected using a Schirmer strip. RESULTS: In 45 recruited RIS patients, OCBs were detected in CSF for 55% (25/45) and in tears for 50% (21/42) of samples. CONCLUSIONS: We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with RIS and be useful in follow-up.

[Medical liability issues]. / Aspects médico-légaux.

Of the 1603 civil liability cases filed between 2002 and 2012 related to upper-limb surgery, we found 20 proceedings (11 in court and 9 in front of the French CCI [commission for medical accidents]) that involved a total of 24 physicians: three proceedings involved multiple parties for a single patient and implicated two physicians in two cases and three physicians in one case. The grounds for liability being invoked varied greatly, but a good many of these cases concerned outcomes that were deemed unsatisfactory or insufficient in light of the initial injury. Information is always difficult to convey in an emergency setting, but is not generally disputed. However, the information process must be completed during the postoperative period and the patient informed of the injury assessment, expected results, potential complications and the possibility of surgical revision in the medium term. An expert found grounds for physician liability and breach of best practices in only three cases. In summary, this study shows that trauma-related flexor tendon injuries are rarely grounds for indictment of physicians before courts of civil jurisdiction (12 per 1000) and findings of liability for breach of best practices are even more rare (2 per 1000).

Demonstration of a lexical access deficit in relapsing-remitting and secondary progressive forms of multiple sclerosis.

The commonly used test to evaluate naming ability in multiple sclerosis (MS) is the Boston Naming Test (BNT). In previous studies the BNP has not shown any specific deficit in MS patients. The BNT score is obtained by adding spontaneously correct answers to correct answers obtained after semantic and phonological clues are given. Our hypothesis was that due to a lexical access deficit based on executive dysfunction, MS patients would need more clues than control subjects to normalize their performances,. Fifteen relapsing-remitting (RR) and 17 secondary progressive (SP) MS patients, and 32 controls matched for sex, age, and educational level, took the BNT. The 32 MS patients also took the BCCog (Short French battery used in MS to evaluate cognitive functions) in order to evaluate their executive functions. MS patients needed significantly more clues than matched controls to normalize their performances (P<0.001). This lexical access deficit was more frequent in the SP than in the RR group (P<0.05). A lexical access deficit inducing a denomination problem has thus been shown in MS patients. Further research should aim to better evaluate the executive functions of patients with a lexical access deficit.