Disease-modifying therapy for multiple sclerosis in Slovenia: analysis of 20 years of treatment

Introduction: Disease-modifying therapy (DMT) dramatically influenced the management of re- lapsing-remitting multiple sclerosis (RRMS). Novel medicines have been developing constantly and therapeutic strategy has changed. We aimed to analyse the development of DMT for MS in Slovenia with a special emphasis on contemporary approaches to the patient management. Materials and Methods: Prescriptions of all DMT in Slovenia from 2001-2021 were analysed as well as re- ferrals to the Committee for MS DMT the Centre for MS in Ljubljana in the last three years (2019-2021). Results: Altogether approximately 360 patients were on DMT in 2001 and 1839 in 2021. The total number of patients on injectable therapies decreased through time while the number of patients on oral therapies increased. Dimethyl fumarate is currently the most frequently used medicine with 505 patients on the drug in 2021. The number of patients on potent medications increased from 28 (3%) in 2012 to 763 (41%) in 2021. Highly active medicines represented 52%, 62% and 69% of all DMT approvals in 2019, 2020 and 2021, respectively. Conclusions: The number of treated MS patients has been increasing steadily in Slovenia as well as the number of patients on potent DMT which proves that neurologists follow the modern concept of MS treatment

Disease-modifying therapy for multiple sclerosis in Slovenia: analysis of 20 years of treatment

Introduction: Disease-modifying therapy (DMT) dramatically influenced the management of re- lapsing-remitting multiple sclerosis (RRMS). Novel medicines have been developing constantly and therapeutic strategy has changed. We aimed to analyse the development of DMT for MS in Slovenia with a special emphasis on contemporary approaches to the patient management. Materials and Methods: Prescriptions of all DMT in Slovenia from 2001-2021 were analysed as well as re- ferrals to the Committee for MS DMT the Centre for MS in Ljubljana in the last three years (2019-2021). Results: Altogether approximately 360 patients were on DMT in 2001 and 1839 in 2021. The total number of patients on injectable therapies decreased through time while the number of patients on oral therapies increased. Dimethyl fumarate is currently the most frequently used medicine with 505 patients on the drug in 2021. The number of patients on potent medications increased from 28 (3%) in 2012 to 763 (41%) in 2021. Highly active medicines represented 52%, 62% and 69% of all DMT approvals in 2019, 2020 and 2021, respectively. Conclusions: The number of treated MS patients has been increasing steadily in Slovenia as well as the number of patients on potent DMT which proves that neurologists follow the modern concept of MS treatment

N-terminal and mid-region tau fragments as fluid biomarkers in neurological diseases

Brain-derived tau secreted into CSF and blood consists of different N-terminal and mid-domain fragments, which may have a differential temporal course and thus, biomarker potential across the Alzheimer's disease continuum or in other neurological diseases. While current clinically validated total-tau (t-tau) assays target mid-domain epitopes, comparison of these assays with new biomarkers targeting N-terminal epitopes using the same analytical platform may be important to increase the understanding of tau pathophysiology. We developed three t-tau immunoassays targeting specific N-terminal (NTA and NTB t-tau) or mid-region (MR t-tau) epitopes, using single molecule array technology. After analytical validation, the diagnostic performance of these biomarkers was evaluated in CSF and compared with the Innotest t-tau (and as proof of concept, with N-p-tau181 and N-p-tau217) in three clinical cohorts (n = 342 total). The cohorts included participants across the Alzheimer's disease continuum (n = 276), other dementia (n = 22), Creutzfeldt-Jakob disease (n = 24), acute neurological disorders (n = 18) and progressive supranuclear palsy (n = 22). Furthermore, we evaluated all three new t-tau biomarkers in plasma (n = 44) and replicated promising findings with NTA t-tau in another clinical cohort (n = 50). In CSF, all t-tau biomarkers were increased in Alzheimer's disease compared with controls (P < 0.0001) and correlated with each other (rs = 0.53-0.95). NTA and NTB t-tau, but not other t-tau assays, distinguished amyloid-positive and amyloid-negative mild cognitive impairment with high accuracies (AUCs 84% and 82%, P < 0.001) matching N-p-tau217 (AUC 83%; DeLong test P = 0.93 and 0.88). All t-tau assays were excellent in differentiating Alzheimer's disease from other dementias (P < 0.001, AUCs 89-100%). In Creutzfeldt-Jakob disease and acute neurological disorders, N-terminal t-tau biomarkers had significantly higher fold changes versus controls in CSF (45-133-fold increase) than Innotest or MR t-tau (11-42-fold increase, P < 0.0001 for all). In progressive supranuclear palsy, CSF concentrations of all t-tau biomarkers were similar to those in controls. Plasma NTA t-tau concentrations were increased in Alzheimer's disease compared with controls in two independent cohorts (P = 0.0056 and 0.0033) while Quanterix t-tau performed poorly (P = 0.55 and 0.44). Taken together, N-terminal-directed CSF t-tau biomarkers increase ahead of standard t-tau alternatives in the Alzheimer's disease continuum, increase to higher degrees in Creutzfeldt-Jakob disease and acute neurological diseases and show better potential than Quanterix t-tau as Alzheimer's disease blood biomarkers. For progressive supranuclear palsy, other tau biomarkers should still be investigated

Diagnostic value of kappa free light chain index in patients with primary progressive multiple sclerosis – a multicentre study

BackgroundKappa free light chains (κ-FLC) in the cerebrospinal fluid (CSF) are an emerging biomarker in multiple sclerosis (MS).ObjectiveTo investigate whether κ-FLC index has similar diagnostic value in patients with primary progressive multiple sclerosis (PPMS) compared to oligoclonal bands (OCB).MethodsPatients with PPMS were recruited through 11 MS centres across 7 countries. κ-FLC were measured by immunonephelometry/-turbidimetry. OCB were determined by isoelectric focusing and immunofixation.ResultsA total of 174 patients (mean age of 52±11 years, 51% males) were included. κ-FLC index using a cut-off of 6.1 was positive in 161 (93%) and OCB in 153 (88%) patients.Conclusionκ-FLC index shows similar diagnostic sensitivity than OCB in PPMS

AUTOMATION OF MUFFLE-FURNACE FOR THICK ANNEALING

Naloga opisuje delo inženirja za krmilnike pri zamenjavi krmilnega dela peči iz ožičene logike v krmiljenje in vodenje preko programirljivo logičnega krmilnika. V nalogi je opisan potek prenosa fizičnih funkcij regulacije iz ožičene logike, v program, ki teče na programirljivem logičnem krmilniku PLK SIEMENS SIMATIC S7 315-2DP. V nadaljevanju je še opis upravljanja recepture, ki se ravno tako nahaja v krmilniku, povezava z 2. nivojem vodenja in izdelava vmesnika SCADA s programskim orodjem WinCC Flexible 2005.This paper describes the work of an engineer for PLC`s in process of including a PLC and replacing wired part of analog temperature control of a furnace for annealing heavy plate. There is a description of process of transfer physical functions of regulation from wired logic to a program that runs on a PLC - SIEMENS SIMATIC S7 315 2DP. Further follows the description of managing a recipe, which is also located in a PLC, linking with level 2 control and making SCADA interface with programming tool WinCC Flexible 2005

Comparison of the MARS-5 score and the weighted CMA7 adherence measure.

Comparison of the MARS-5 score and the weighted CMA7 adherence measure.</p

S1 Data -

The 5-item Medication Adherence Report Scale (MARS-5) is a reliable and valid questionnaire for evaluating adherence in patients with asthma, hypertension, and diabetes. Validity has not been determined in multiple sclerosis (MS). We aimed to establish criterion validity and reliability of the MARS-5 in persons with MS (PwMS). Our prospective study included PwMS on dimethyl fumarate (DMF). PwMS self-completed the MARS-5 on the same day before baseline and follow-up brain magnetic resonance imaging (MRI) 3 and 9 months after treatment initiation and were graded as highly and medium adherent upon the 24-cut-off score, established by receiver operator curve analysis. Health outcomes were represented by relapse occurrence from the 1st DMF dispense till follow-up brain MRI and radiological progression (new T2 MRI lesions and quantitative analysis) between baseline and follow-up MRI. Criterion validity was established by association with the Proportion of Days Covered (PDC), new T2 MRI lesions, and Beliefs in Medicines questionnaire (BMQ). The reliability evaluation included internal consistency and the test-retest method. We included 40 PwMS (age 37.6 ± 9.9 years, 75% women), 34 were treatment-naive. No relapses were seen during the follow-up period but quantitative MRI analysis showed new T2 lesions in 6 PwMS. The mean (SD) MARS-5 score was 23.1 (2.5), with 24 PwMS graded as highly adherent. The higher MARS-5 score was associated with higher PDC (b = 0.027, P0.001, 95% CI: (0.0134–0.0403)) and lower medication concerns (b = -1.25, P0.001, 95% CI: (-1.93-(-0,579)). Lower adherence was associated with increased number (P = 0.00148) and total volume of new T2 MRI lesions (P = 0.00149). The questionnaire showed acceptable internal consistency (Cronbach α = 0.72) and moderate test-retest reliability (r = 0.62, P </div

Timeline of the prospective study, *120 mg twice daily, **240 mg twice daily, Rx-refills.

Timeline of the prospective study, *120 mg twice daily, **240 mg twice daily, Rx-refills.</p

Scatterplot of the weighted CMA 7 measure and the MARS-5 at the follow-up brain MRI, number of PwMS N = 40.

Scatterplot of the weighted CMA 7 measure and the MARS-5 at the follow-up brain MRI, number of PwMS N = 40.</p