Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

Detecting disability using self-reported and clinical assessments in early-stage relapsing-remitting multiple sclerosis: Looking for a complementary approach.

Disability accrual is mainly driven by progression independent of relapse activity, which is present even in early stages of relapsing-remitting multiple sclerosis (RRMS) and sometimes overlooked. This multicenter, non-interventional study evaluated whether patient-reported outcomes measures (PROMs) could capture disability in 189 early-stage RRMS patients (mean age: 36.1 ± 9.4 years, 71.4% female, mean disease duration: 1.4 ± 0.8 years, median EDSS: 1.0). The 9-Hole Peg Test (9-HPT), NeuroQoL Upper Extremity (NeuroQoL-UE), Timed 25-Foot Walk (T25-FW), Multiple Sclerosis Walking Scale (MSWS-12), Symbol Digit Modalities Test (SDMT), and Perceived Deficits Questionnaire (PDQ-5) were used to assess hand function, gait, and cognition, respectively. These functions were at least mildly affected in this early-stage population, finding significant correlations between PROMs and clinical assessments. PROMs could enable early-stage RRMS patients to communicate their perceived disability in different domains, assisting clinicians in disease monitoring and decision making.

Expert-Agreed Practical Recommendations on the Use of Cladribine.

Cladribine is a disease-modifying selective immune reconstitution oral therapy for adult patients with highly active relapsing multiple sclerosis (RMS). It was approved in the USA in 2019 and in Europe in 2017, thus there are still gaps in existing guidelines for using cladribine tablets in clinical practice. Nine experts with extensive experience in managing patients with multiple sclerosis in Spain identified some of the unanswered questions related to the real-life use of cladribine tablets. They reviewed the available clinical trial data and real-world evidence, including their own experiences of using cladribine, over the course of three virtual meetings held between November 2020 and January 2021. This article gathers their practical recommendations to aid treatment decision-making and optimise the use of cladribine tablets in patients with RMS. The consensus recommendations cover the following areas: candidate patient profiles, switching strategies (to and from cladribine), managing response to cladribine and safety considerations.

Long-term prognosis communication preferences in early-stage relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their future lives. Improving communication strategies on prognosis may help patients deal with the disease and adjust their long-term life goals. However, there is limited information on patients' preferences of long-term prognosis (LTP) communication and associated factors. OBJECTIVE: The aim of this study was to describe patients' preferences and assess the factors associated with LTP communication preferences in early-stage relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration from first attack ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The Prognosis in MS questionnaire was used to assess how much patients want to know about their LTP. Different patient-reported measures were administered to gather information on symptom severity, pain, fatigue, mood/anxiety, quality of life, stigma, illness perception, feeling of hopelessness, self-efficacy, information avoidance and coping strategies. Cognition was assessed using the Symbol Digit Modalities Test (SDMT). A multivariate logistic regression analysis was performed to assess the association between LTP information preference and demographic and clinical characteristics, as well as patients' perspectives. RESULTS: A total of 189 patients were included (mean age: 36.1  ±  9.4 years, 71.4% female, mean disease duration: 1.2  ±  0.8 years). Median EDSS score was 1.0 (IQR = 0.0-2.0). A proportion of 68.5% (n  =  126) of patients had never discussed LTP with their neurologists, whereas 69.2% (n = 126) reported interest in knowing it (73.5% at diagnosis). Bivariate analyses suggested that patients were significantly more likely to have higher LTP information preferences if they were male and had a lower SDMT score. Male gender and a lower SDMT score were predictors of LTP information preferences. CONCLUSIONS: Patients with early-stage RRMS want to discuss their LTP shortly after diagnosis. Understanding the factors involved may be useful to design individualized communication strategies.

Measuring productivity loss in early relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their autonomy and capacity to maintain employment. OBJECTIVE: The aim of this study was to assess the impact on work productivity in early-stage relapsing-remitting multiple sclerosis (RRMS). METHODS: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. Absenteeism, presenteeism, and unpaid work loss due to RRMS were measured using the Valuation of Lost Productivity (VOLP) questionnaire. The EDSS, SymptoMScreen, 5-item Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, Symbol Digit Modalities Test, and Multiple Sclerosis Work Difficulties Questionnaire were used to gather information on disability, patients' perception of symptom severity, fatigue, mood/anxiety, cognition, and problems in the workplace, respectively. Associations between the VOLP and clinical and work outcomes were analyzed using Spearman's rank correlations. RESULTS: A total of 189 patients were included. Mean age (SD) was 36.1 ± 9.4 years and 71.4% were female. Mean disease duration was 1.2 ± 0.8 years. Median EDSS score was 1.0 (IQR 0, 2.0). One hundred thirty patients (68.8%) were working for pay or self-employed. Fifty-three patients (40.8%) reported absence from work in the past 3 months with an average of 14.3 absent workdays. Their health problems resulted in the loss of 3.4% of their actual work time in the past 7 days. Thirty patients got help (11.8 h) with their unpaid work activities in the past 7 days. Absenteeism was significantly correlated with anxiety and depression (rho=0.298 and 0.291, p<0.001), fatigue (rho=0.214, p = 0.014), and symptom severity (rho=0.213, p = 0.015). Presenteeism was significantly correlated with fatigue (rho=0.375, p<0.001), symptom severity (rho=0.373, p<0.001), depression (rho=0.263, p = 0.008), and disability (rho=0.215, p = 0.031). CONCLUSIONS: Productivity loss even in a RRMS population with short disease duration stresses the need for more efficient treatment control of disease activity from earlier stages.

Diferencias clínicas y terapéuticas de la afectación neurooftalmológica secundaria a sífilis / Clinical and therapeutic differences in neuro-ophthalmological involvement secondary to syphilis

Introducción. Existen múltiples formas de afectación neurooftalmológica secundaria a sífilis, no siempre bien conocidas. Nuestro objetivo es conocer las diferencias clínicas y de tratamiento en estos pacientes. Casos clínicos. Se incluyeron ocho pacientes diagnosticados de afectación ocular y neurooftalmológica por sífilis durante los años 2012 y 2013. Cinco presentaron uveítis, siendo la panuveítis la forma más frecuente, con tres casos. Dos casos presentaron papiledema, y otro, neuropatía óptica retrobulbar. Un 62,5% fue diagnosticado de neurosífilis, cuya presencia se relacionó con la afectación del nervio óptico (p = 0,035). Ninguno de ellos presentó positividad para VDRL en el líquido cefalorraquídeo, y se diagnosticaron por la presencia de anticuerpos FTA junto con hiperproteinorraquia, pleocitosis linfocitaria o síntesis intratecal de anticuerpos. En ausencia de uveítis, se produjo un retraso diagnóstico medio de 2,6 meses (p = 0,047). Todos los pacientes, salvo uno que precisó vitrectomía, evolucionaron favorablemente con antibioterapia intravenosa. Conclusiones. En casos de afectación neurooftalmológica, inflamatoria y no inflamatoria, el clínico debe tener en cuenta la sífilis como potencial etiología para evitar un retraso diagnóstico, puesto que un adecuado tratamiento precoz puede evitar una pérdida de visión permanente (AU)

Introduction. There are many forms of neuro-ophthalmological involvement secondary to syphilis, and not all of them are well known. Our aim is to determine the clinical and therapeutic differences in these patients. Case reports. Our sample included eight patients diagnosed with an ocular and neuro-ophthalmological disorder due to syphilis over the years 2012 and 2013. Five of them presented uveitis, pan-eveitis being the most frequent, with three cases. Two cases presented papilloedema and another displayed retrobulbar optic neuropathy. A total of 62.5% were diagnosed with neurosyphilis, the presence of which was related with compromise of the optic nerve (p = 0.035). None of them gave positive for VDRL in cerebrospinal fluid and they were diagnosed by the presence of FTA antibodies together with high protein levels in cerebrospinal fluid, lymphocytic pleocytosis or intrathecal synthesis of antibodies. In the absence of uveitis, diagnosis was delayed by a mean time of 2.6 months (p = 0.047). All the patients, except one who required a vitrectomy, progressed favourably with intravenous antibiotic therapy. Conclusions. In cases of neuro-ophthalmological compromise, whether inflammatory or non-inflammatory, the physician must bear syphilis in mind as a potential causation in order to avoid delays in the diagnosis, since early well-tailored treatment can prevent permanent loss of sight(AU)

Stressed cybrids model demyelinated axons in multiple sclerosis.

Multiple sclerosis is likely caused by a complex interaction of multiple genes and environmental factors. The contribution of mitochondrial DNA genetic backgrounds has been frequently reported. To evaluate the effect of mitochondrial DNA haplogroups in the same genetic and environmental circumstances, we have built human transmitochondrial cell lines and simulated the effect of axon demyelination, one of the hallmarks of multiple sclerosis pathology, by altering the ionic gradients through the plasmalemma and increasing ATP consumption. In this model, mitochondrial biogenesis is observed. This process is larger in Uk cybrids, which mirrors their lower oxidative phosphorylation capacity in basal conditions. This model replicates a process occurring in both patients suffering from multiple sclerosis and several animal models of axon demyelination. Therefore, it can be used to analyze the contribution of various mitochondrial DNA genotypes to multiple sclerosis. In this sense, a longer or stronger energy stress, such as that associated with demyelinated axons in multiple sclerosis, could make Uk individuals more susceptible to this pathology. Finally, pharmacologic compounds targeted to mitochondrial biogenesis could be a potential therapy for multiple sclerosis.

Respuesta: Supervivencia de la parada cardiorrespiratoria hospitalaria / Author’s reply: Survival from in-hospital cardiac arrest

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Características de la parada cardiorrespiratoria en el paciente con accidente cerebrovascular / No disponible

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[Do not resuscitate orders in patients with acute stroke. What circumstances decide their use?]. / Factores determinantes en la aplicación de las órdenes de no reanimación en el ictus.

BACKGROUND: Patients with acute stroke are known to have a poor prognosis after cardiopulmonary resuscitation manoeuvres (CPR), and their application should be revisited in these patients. Although clinical criteria for a 'do not resuscitate order' (DNR) are available in some countries, studies about DNR in stroke are lacking in Spain. The purpose of this study was to evaluate the frequency of DNR orders in patients with acute stroke and to identify factors influencing decision-making in them. PATIENTS AND METHOD: All patients with acute stroke who had cardiac and pulmonary arrest were prospectively included in the study during one year. Clinical and demographic data of patients and data related to doctors were recorded and analysed. RESULTS: 165 patients had a cardiac and pulmonary arrest and 17 (10%) of them had had a DNR order. No factor was significantly associated with DNR decision-making. CONCLUSIONS: DNR orders were scarcely applied and explicit clinical criteria for their application were lacking. It is necessary to implement DNR policies in Spain in order to improve the use of CPR manoeuvres in patients with acute stroke.

Factores determinantes en la aplicación de las órdenes de no reanimación en el ictus / Do not resuscitate orders in patients with acute stroke. What circumstances decide their use?

FUNDAMENTO: El ictus es uno de los procesos con peores resultados tras una reanimación cardiopulmonar, por lo que la aplicación de una orden de no reanimación (ONR) es una práctica que debería considerarse en todo paciente con ictus agudo. Aunque hay algún trabajo sobre cuándo indicar una ONR en los pacientes con ictus, en España no se conoce la incidencia de las ONR ni los factores que influyen en la toma de decisión. El objetivo de nuestro estudio fue conocer la frecuencia y los determinantes con los que se establecen las ONR a los pacientes con ictus en nuestro medio. PACIENTES Y MÉTODO: Estudio prospectivo de los pacientes con ictus agudo que sufren una parada cardiorrespiratoria (PCR) durante su ingreso en un hospital terciario en el período 1996-1997. Se analizó la influencia de una serie de variables técnicas (nivel de conciencia, situación clínica, tipo y gravedad del ictus, comorbilidad significativa, daño cerebral amenazante) y otras no estrictamente técnicas (edad, sexo, capacidad de comunicación del paciente y ubicación de éste durante el ingreso) sobre la decisión de ONR. RESULTADOS: Sufrieron una PCR 165 pacientes. Un 10 por ciento había recibido una ONR. Ninguna variable influyó de forma significativa sobre la decisión de ONR. CONCLUSIONES: La incidencia de aplicación de ONR en nuestro ámbito es escasa y se aplica sin criterios explícitos. Es necesaria la implantación de políticas hospitalarias de ONR en España, para mejorar el uso de las maniobras de reanimación cardiopulmonar (AU)