Cost associated with a relapse-free patient in multiple sclerosis: a real-world health indicator

Background: The efficacy and safety of disease-modifying therapies (DMTs) in multiple sclerosis (MS) are well known; however, owing to their high costs, determining real-world outcomes is essential to evaluate the cost-effectiveness of different therapeutic strategies. This study aimed to investigate the variability in the annual cost of DMTs associated with a relapse-free patient in a representative population cohort of relapsing-remitting MS (RRMS), and whether this could serve as an appropriate health indicator. Methods: We analyzed the patients followed up in our MS clinic during the years 2016 and 2019, and selected patients belonging to our health district diagnosed with RRMS. The treatment cost associated with a relapse-free patient was the ratio between the total cost of DMTs and the number of relapse-free patients, treated and not treated, during the year of the study. Results: A total of 158 patients with RRMS in 2016 and 183 in 2019 were included in our study. In 2016, 101 patients with RRMS (63.9%) received treatment with DMTs and 120 patients (75.9%) remained relapse-free. The mean cost of DMTs per patient in 2016 was 7414.3 (95% confidence interval [CI]: 6325.2-8503.4) considering all the patients (treated and not treated). In 2019, 126 patients (68.9%) received DMTs and 151 patients (82.5%) remained relapse-free. The mean cost of DMTs per patient in 2019 was 6985.4 (95% CI: 5986.9-7983.9) considering all the patients. The cost per year of DMTs to achieve a relapse-free patient was 9762.2 in 2016 and 8465.8 in 2019. Conclusions: The treatment cost per year to achieve a relapse-free patient was stable during successive measurements in the same population. Therefore, it may be considered a good real-world health indicator for patients with RRMS treated with DMTs

Neurological toxicity due to antimonial treatment for refractory visceral leishmaniasis

Introduction: Although pentavalent antimonials are no longer considered the first-line therapy for visceral leishmaniasis in the developed world, they are still used in certain geographical areas and in refractory cases. These drugs have a great number of adverse effects; however, neurological toxicity has been rarely reported. Case report: We present a 56-year-old woman who required long-term treatment with antimonial drugs due to refractory visceral leishmaniasis and presented clinically with tremor of extremities, myoclonus, gait disturbances and epileptic seizures. The EEG showed increased beta rhythms and generalized epileptogenic activity. She had a slow but favorable response after the withdrawal of antimonials and the initiation of anticonvulsant therapy. Conclusion: Severe but reversible neurological toxicity is a rare adverse effect of prolonged antimonial treatment. More EEG record data are needed to support the suspicion of a possible increase of beta rhythms in this situation. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V

Baseline MxA mRNA expression predicts interferon beta response in multiple sclerosis patients

Background Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta. Methods Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups. Results 104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers. Conclusion The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment

The age at onset of relapsing-remitting multiple sclerosis has increased over the last five decades

Background: Patients with relapsing-remitting multiple sclerosis (RRMS) most commonly experience their first symptoms between 20 and 40 years of age. The objective of this study was to investigate how the age at which the first symptoms of RRMS occur has changed over the past decades. Methods: Patients who were followed up in our unit after an initial diagnosis of RRMS using the Poser or McDonald criteria and who experienced their first symptoms between January 1970 and December 2019 were included in the study. The cohort was divided into five groups according to the decade in which the first symptoms appeared. The age at disease onset was compared across decades. Changes in age were also determined after excluding patients with early-onset disease (50 years of age) to avoid bias. Results: The cohort included 1,622 patients with RRMS, 67.6% of whom were women. Among them, 5.9% and 4% had early-onset and late-onset disease, respectively. The mean age ± standard deviation at onset was 31.11 ± 9.82 years, with no differences between men and women. The mean ages at onset were 23.79 ± 10.19 years between 1970 and 1979, 27.86 ± 9.22 years between 1980 and 1989, 30.07 ± 9.32 years between 1990 and 1999, 32.12 ± 9.47 between 2000 and 2009, and 34.28 ± 9.83 years between 2010 and 2019. The ages at disease onset were progressively higher in the later decades; this trend was statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.264 and R2 of 0.070 (p < 0.001). The results were similar when analysing men and women separately. We conducted an analysis of 1,460 patients (mean age at onset: 31.10 ± 7.99 years), after excluding patients with early-onset and late-onset disease. In this specific subgroup, the mean ages at disease onset were 28.38 ± 8.17 years between 1970 and 1979, 29.22 ± 7.51 years between 1980 and 1989, 30.06 ± 8.02 years between 1990 and 1999, 31.46 ± 7.77 years between 2000 and 2009, and 33.37 ± 7.97 years between 2010 and 2019. The trend was also statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.193 and R2 of 0.037 (p < 0.001)

Individualización posológica de natalizumab en la esclerosis múltiple remitente recurrente

La esclerosis multiple (EM) es la enfermedad autoinmune, inflamatoria, cronica y degenerativa mas prevalente a nivel mundial, cuya forma mas frecuente es la EM remitente recurrente (EMRR). Para el manejo de la EMRR grave se aprobo natalizumab, un anticuerpo monoclonal IgG4 que se une a la integrina 41 de la superficie de los leucocitos, impidiendo que migren al sistema nervioso central. Con la dosis fija intravenosa aprobada, de 300 mg cada 4 semanas, se ha comprobado que mas del 90% de los pacientes alcanzan concentraciones sericas preinfusion de NTZ >10 μg/mL, cuando la eficacia se ha demostrado con unos niveles de 2,5-10 μg/mL. Una concentracion plasmatica de NTZ de 2,5 μg/mL asegura una ocupacion del 50% de la biofase y demuestra una eficacia terapeutica, mientras que tasas de ocupacion del 20-40% se han relacionado con un aumento de la actividad de la enfermedad. Palabras clave: Esclerosis multiple, natalizumab, farmacocinétic

Kappa free light chains index in multiple sclerosis very long-term prognosis

IntroductionThe role of the kappa-free light chain (kFLC) in the diagnosis of multiple sclerosis (MS) and, to a lesser extent, its role as a medium-term prognostic marker have been extensively studied. This study aimed to explore its potential as a long-term prognostic marker for MS.MethodsWe performed an exploratory retrospective observational study by selecting patients systemically followed up in our MS unit with available cerebrospinal fluid and serum samples at the time of initial evaluation. Two groups were defined: benign MS (bMS), defined as patients with Expanded Disability Status Scale (EDSS) ≤ 3 at 10 years of follow-up, and aggressive MS (aMS), defined as patients with EDSS ≥ 6 at 15 years of follow-up. Clinical variables were collected, and the immunoglobulin G (IgG) index, kFLC index, and oligoclonal bands (OCB) were determined for all patients and compared between the groups.ResultsTwenty bMS and 15 aMS patients were included in this study. Sixty percent (21/35) were female, and the mean age at the time of the first symptom was 31.5 ± 9.45 years, with no statistical differences between groups. Median follow-up time was 19.8 years (Interquartile range, IQR 15.9–24.6). The median EDSS scores at the last follow-up were 1.5 and 7.5 in the bMS and the aMS group, respectively. No statistically significant differences were found in the kFLC index between the two groups (136.6 vs. 140.27, p=0.59). The IgG index was positive in 62.9% of patients (55% bMS vs. 73.3% aMS, p&gt;0.05), and OCB was positive in 88.6% (90% bMS vs. 86.7% aMS, p&gt;0.05). A significant positive correlation was found between IgG and kFLC indices (rs = 0.85, p&lt;0.001).ConclusionGiven the absence of differences between the two groups with opposite disease courses, it is unlikely that the kFLC index is a reliable and powerful marker of long-term prognosis in MS

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Expresión del gen de la proteína MxA como biomarcador de respuesta al interferón beta en pacientes con esclerosis múltiple

[spa] El Interferón beta (IFN-β) es uno de los tratamientos más ampliamente utilizados para la Esclerosis múltiple (EM). Se trata de una citoquina que actúa a través de su unión a un receptor de elevada afinidad en la superficie celular. Esto provoca la transcripción de factores que modifican la expresión génica, dando lugar a proteínas responsables del efecto antiviral, antiproliferativo y antiinflamatorio, tales como la proteína Mixovirus resistance A (MxA). Desafortunadamente, no todos los pacientes responden adecuadamente al tratamiento. Disponer de biomarcadores que faciliten la selección del tratamiento más óptimo para cada paciente se ha convertido en un objetivo de las investigaciones actuales. La expresión del gen de la proteína MxA se ha propuesto como biomarcador de respuesta al tratamiento con IFN-β desde dos enfoques: como indicador del estado de la vía de señalización del interferón tipo I y como indicador de biodisponibilidad del IFN-β una vez instaurado el tratamiento. Con el objetivo de estudiar la utilidad de la expresión de MxA como biomarcador de respuesta al tratamiento con IFN-β se seleccionando 104 pacientes diagnosticados de EM a los que se siguió de forma prospectiva y se obtuvieron muestras de sangre, previo inicio de tratamiento, a los 3 y a los 12 meses. Se realizó una PCR a tiempo real para evaluar la expresión del mRNA MxA. Para evaluar el estado de la vía de señalización del interferón, se llevaron a cabo los dos primeros trabajos: en el primero, se evalúa la expresión basal de MxA previo inicio del tratamiento. Los resultados muestran que el tiempo hasta el siguiente brote y hasta la progresión de la discapacidad es mayor en pacientes con expresión basal reducida de mRNA MxA, teniendo además la expresión basal de mRNA MxA, capacidad para predecir una buena respuesta al tratamiento con un valor predictivo positivo del 77%. En el segundo trabajo, se realiza un análisis de variables clínicas, radiológicas y de laboratorio de los pacientes que inician tratamiento con IFN-β. Aquellos pacientes que además de presentar una expresión basal incrementada de mRNA MxA, también presentan una mayor discapacidad basal y una menor inducción de MxA a los tres meses de iniciar el tratamiento, tienen mayor probabilidad de no responder adecuadamente al IFN-β evaluado como el tiempo hasta el siguiente brote. Para evaluar la biodisponibilidad del IFN-β una vez iniciado el tratamiento se llevó a cabo el tercer trabajo. En éste, se estudia la expresión de MxA después de un año de tratamiento con IFN-β y se evalúa la evolución clínica posterior. Los pacientes con expresión más elevada de mRNA MxA al año de tratamiento tardan más tiempo hasta el siguiente brote y hasta la progresión de la discapacidad. Por el contrario, aquellos con una expresión reducida presentaban antes tanto brotes como progresión de la discapacidad. Estos estudios nos permiten obtener las siguientes conclusiones: que la detección de una expresión basal de mRNA MxA baja puede ser un biomarcador útil para identificar pacientes diagnosticados de EMRR con elevada probabilidad de respuesta clínica al tratamiento con IFN- β. Que la presencia de una mayor inducción del mRNA MxA a los tres meses de haber iniciado el tratamiento se asocia a una mayor probabilidad de responder clínicamente al IFN-β y por último que la detección de una expresión reducida de mRNA MxA al año de iniciar el tratamiento con IFN-β se relaciona con una pérdida de respuesta clínica al tratamiento con IFN-β.[eng] Interferon beta (IFN-β) is one of the most common therapies used for multiple sclerosis (MS). Unfortunately, not all patients respond properly to MS therapies. It would be of value being able to determine whether a patient will respond or not to each type of treatment. Myxovirus resistance protein A (MxA) is a molecule induced after injection of IFN-β, and its quantification could be considered a biomarker of response to IFN-β therapy from two points of view: first as an indicator of the type I IFN pathway and second as an IFN-β bioavailability marker. To study MxA, 104 patients were selected and followed in a prospective manner. Blood samples were obtained before starting treatment and after 3 and 12 months of IFN-β. Real time PCR was performed to study mRNA MxA expression. In the first work, baseline expression of mRNA MxA was evaluated. The results showed that time to next relapse and to disability progression were longer in patients with lower baseline MxA mRNA levels, and this may be useful for predicting whether patients will respond or not to IFN-β, with a positive predictive value of 77%. In the second work, clinical, radiologic and laboratory variables were evaluated. The subgroup of MS patients whose baseline profile was consistent with greater disability, high baseline MxA, and low MxA induction after 3 months of treatment had a higher probability of non-responding to IFN-β than their counterparts. In the third work, mRNA MxA expression at one year was studied. Detection of mRNA MxA induction could be a useful parameter to identify patients who will respond to IFN-β treatment, defined as longer time to next relapse and to disability progression. The conclusions are: 1. Baseline mRNA MxA expression could be a useful biomarker to identify MS patients with high probability of clinical response to IFN-β treatment. 2.Detection of greater induction of mRNA MxA after 3 months of IFN-β treatment is associated with a greater probability of clinical response to IFN-β. 3. Detection of a reduced expression of mRNA MxA after one year of IFN-β treatment is related with a loss of clinical response to IFN-β