Therapeutic inertia in the management of neuromyelitis optica spectrum disorder.

Introduction and objective: Limited information is available on how neurologists make therapeutic decisions in neuromyelitis optica spectrum disorder (NMOSD), especially when new treatments with different mechanisms of action, administration, and safety profile are being approved. Decision-making can be complex under this uncertainty and may lead to therapeutic inertia (TI), which refers to lack of treatment initiation or intensification when therapeutic goals are not met. The study aim was to assess neurologists' TI in NMOSD. Methods: An online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists answered a survey composed of demographic characteristics, professional background, and behavioral traits. TI was defined as the lack of initiation or intensification with high-efficacy treatments when there is evidence of disease activity and was assessed through five NMOSD aquaporin-4 positive (AQP4+) simulated case scenarios. A multivariate logistic regression analysis was used to determine the association between neurologists' characteristics and TI. Results: A total of 78 neurologists were included (median interquartile range [IQR] age: 36.0 [29.0-46.0] years, 55.1% male, median [IQR] experience managing demyelinating conditions was 5.2 [3.0-11.1] years). The majority of participants were general neurologists (59.0%) attending a median (IQR) of 5.0 NMOSD patients (3.0-12.0) annually. Thirty participants (38.5%) were classified as having TI. Working in a low complexity hospital and giving high importance to patient's tolerability/safety when choosing a treatment were predictors of TI. Conclusion: TI is a common phenomenon among neurologists managing NMOSD AQP4+. Identifying TI and implementing specific intervention strategies may be critical to improving therapeutic decisions and patient care.

Value contribution of blood-based neurofilament light chain as a biomarker in multiple sclerosis using multi-criteria decision analysis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease that represents a leading cause of non-traumatic disability among young and middle-aged adults. MS is characterized by neurodegeneration caused by axonal injury. Current clinical and radiological markers often lack the sensitivity and specificity required to detect inflammatory activity and neurodegeneration, highlighting the need for better approaches. After neuronal injury, neurofilament light chains (NfL) are released into the cerebrospinal fluid, and eventually into blood. Thus, blood-based NfL could be used as a potential biomarker for inflammatory activity, neurodegeneration, and treatment response in MS. The objective of this study was to determine the value contribution of blood-based NfL as a biomarker in MS in Spain using the Multi-Criteria Decision Analysis (MCDA) methodology. Materials and methods: A literature review was performed, and the results were synthesized in the evidence matrix following the criteria included in the MCDA framework. The study was conducted by a multidisciplinary group of six experts. Participants were trained in MCDA and scored the evidence matrix. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. Results: MS was considered a severe condition as it is associated with significant disability. There are unmet needs in MS as a disease, but also in terms of biomarkers since no blood biomarker is available in clinical practice to determine disease activity, prognostic assessment, and response to treatment. The results of the present study suggest that quantification of blood-based NfL may represent a safe option to determine inflammation, neurodegeneration, and response to treatments in clinical practice, as well as to complement data to improve the sensitivity of the diagnosis. Participants considered that blood-based NfL could result in a lower use of expensive tests such as magnetic resonance imaging scans and could provide cost-savings by avoiding ineffective treatments. Lower indirect costs could also be expected due to a lower impact of disability consequences. Overall, blood-based NfL measurement is supported by high-quality evidence. Conclusion: Based on MCDA methodology and the experience of a multidisciplinary group of six stakeholders, blood-based NfL measurement might represent a high-value-option for the management of MS in Spain.

Preferences for neuromyelitis optica spectrum disorder treatments: A conjoint analysis with neurologists in Spain.

BACKGROUND: The treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles. OBJECTIVE: The aim of this study was to assess neurologists' preferences for different NMOSD treatment attributes using conjoint analysis (CA). METHODS: We conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs' attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences. RESULTS: A total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts. CONCLUSION: Neurologists' treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition.

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.

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.

Medical help-seeking intentions among patients with early Alzheimer's disease.

Background: Limited information is available on the active process of seeking medical help in patients with Alzheimer's disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors. Methods: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer's Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5-1.0. A multivariate logistic regression analysis was conducted. Results: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016). Conclusion: Understanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition.

Adaptación al castellano de la escala Clinically Useful Depression Outcome Scale (cudos) para la evaluación de la depresión mayor desde la perspectiva del paciente / Adaptation into spanish of the Clinically Useful Depression Outcome Scale (cudos) for assessing major depressive disorder from the patient’s perspective

Objetivo: Adaptar al castellano la escala CUDOS (Clinically Useful Depression Outcome Scale) y analizar sus propiedades psicométricas en pacientes con trastorno depresivo mayor (TDM).Método: Se realizó un estudio multicéntrico transversal de dos etapas (adaptación cultural y validación psicométrica) en el que se evaluaron pacientes en Atención Primaria con TDM diagnosticado (criterios DSM-IV TR) en los últimos3 meses. Junto a la escala CUDOS, se aplicaron los instrumentos: PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Componentes Físico–PCS- y Mental–MCS-) y escalas CGI-SI y PGI-SI (Escala de Impresión Clínica Global de Gravedad según clínico o paciente, respectivamente).Se analizó la factibilidad, fiabilidad y validez de la versión adaptada. Resultados: En la fase de validación, se incluyeron 305pacientes (69,5% mujeres) con edad media (desviación típica)de 51,75(15,53) años. El tiempo medio de cumplimentación fue de 4,47(±2,4) minutos. Los efectos techo/suelo se encontraron en menos del 1% de los casos. La consistencia interna de la escala CUDOS fue adecuada (α de Cronbach=0,88). Los coeficientes de correlación de Pearson de CUDOS con otras escalas fueron: 0,42 (SOFAS); 0,45 (HAMD-17); -0,22 (PCS);-0,65 (MCS); p<0,001. La escala CUDOS discriminó adecuadamente entre los diferentes niveles clínicos de gravedad (p<0,03).Conclusiones: La versión adaptada de la escala CUDOS muestra propiedades psicométricas adecuadas como instrumento de evaluación de la depresión mayor desde la perspectiva del paciente (AU)

Objective: To adapt the CUDOS scale (Clinically Useful Depression Outcome Scale) into Spanish and to test its psychometrical properties in a sample of patients with major depressive disorder (MDD).Methods: A two-step cross-sectional, multicenter validation study was conducted (linguistic adaptation into Spanish and psychometric validation). The study evaluated patients attended in Primary Care with a MDD diagnosis within the last 3 months (DSM-IV TR criteria). The following scales were administered: CUDOS, PRIME-MD (Primary Care Evaluation of Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and Occupational Functioning Assessment Scale), SF-36 (Physical –PCS- and Mental –MCS- Component Summaries), and the CGI-S &PGI-S (Clinical Global Impression for Severity of Illness scales for clinicians and patients, respectively). Feasibility, reliability, and validity of the Spanish version were assessed. Results: In the validation study, 305 MDD patients (69.5% female) with a mean age (standard deviation-SD-) of 51.75 (15.53) were included. Mean completion time was 4.47 (2.4) minutes. Floor or ceiling effects were found in less than 1% of the case scores. Internal consistency was adequate (Cronbach´s α= 0.88). Pearson correlation coefficients with CUDOS were: -0.42 (SOFAS), 0.45 (HAMD-17), -0.22 (PCS),-0.65 (MCS); all p<0.001. The CUDOS properly discriminated among clinical severity levels (p<0.03). Conclusions: The adapted Spanish version of the CUDOS shows adequate psychometric properties as an evaluation instrument of major depression from the patient’s perspective (AU)

Validación de la versión en castellano de la Escala del Bienestar Subjetivo con Neurolépticos (SWN-K) en pacientes con esquizofrenia / Validation of the Spanish version of the Subjective Well-being under Neuroleptic Scale (SWN-K) in patients with schizophrenia

Fundamento y objetivo: La experiencia subjetiva de los pacientes psicóticos con el tratamiento neuroléptico es un factor clave en la adherencia terapéutica, calidad de vida y pronóstico. El objetivo de este trabajo fue realizar la adaptación cultural al castellano de la Escala del Bienestar Subjetivo con Neurolépticos (SWN-K) y analizar sus propiedades psicométricas en pacientes con esquizofrenia. Pacientes y método: Se realizó un estudio transversal en dos fases (adaptación cultural y validación psicométrica) en el que se incluyó a 97 pacientes mayores de 18 años en tratamiento antipsicótico. Se valoraron la factibilidad, fiabilidad y validez de la escala. Resultados:Se demostró una buena aceptabilidad de la escala SWN-K. El coeficiente α de Cronbach de la puntuación total de la escala SWN-K fue de 0,86. La fiabilidad test-retest fue de 0,88 (intervalo de confianza del 95% [IC 95%] 0,84 y 0,93). La SWN-K discriminó entre los niveles de gravedad de la ICG-G (p < 0,01 ANOVA unilateral) y se observó una tendencia lineal (p<0,001).Conclusiones: La versión adaptada al castellano de la SWN-K muestra propiedades psicométricas adecuadas como instrumento autoadministrado de evaluación del bienestar subjetivo en esquizofrenia (AU)

Background and objective: The subjective experience of patients with psychoses towards neuroleptic treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim was to achieve a linguistic adaptation and psychometric validation into Spanish of the Subjective Well-being under Neuroleptic Scale (SWN-K) among patients with schizophrenia.Material and method: Cross-sectional validation study conducted in two phases (cultural adaptation into Spanish and psychometric validation) in clinically stable patients under antipsychotic treatment. Feasibility and reliability were explored.Results: A total of 97 patients were included. Most patients were male (72%), with mean age of 35 years (SD=10). The SWN-K showed a good acceptability. SWN-K total score Cronbach's α was 0.86. The SWN-K total score test-retest reliability was 0.88 (95% CI=0.84 to 0.93). The SWN-K discriminated among CGI-S levels (one-way ANOVAS P<0.01), showing a linear trend (P<0.001). Conclusions: The Spanish version of the SWN-K is feasible, reliable, and appropriated as a patient-reported outcome to evaluate patients’ subjective well being under treatment (AU)

Costes y factores asociados a las respuestas óptima y subóptima al tratamiento del trastorno depresivo mayor en atención primaria / Costs and associated factors with optimal and suboptimal responses to the treatment of major depressive disorder

Objetivo: Evaluar el cumplimiento, la persistencia y los costes del tratamiento del trastorno depresivo mayor (TDM) en el ámbito de atención primaria, haciendo énfasis en aspectos diferenciales de aquellos pacientes con una respuesta subóptima al tratamiento antidepresivo (AD) inicial. Diseño: Diseño observacional retrospectivo realizado a partir de registros poblacionales de Badalona Serveis Assistencials. Criterios de inclusión: edad ≥ 18 años, inicio del episodio durante 2008-2009 y estar en tratamiento AD al menos 8 semanas tras la primera prescripción. El seguimiento fue de 12 meses. Dos grupos de estudio: pacientes con respuesta subóptima/remisión. Principales mediciones: sociodemográficas, cumplimiento y persistencia del tratamiento, costes sanitarios (directos e indirectos). Resultados: Se analizaron 2.260 sujetos (media edad: 58,8 años, 74% mujeres). El 42,7% (IC95%: 40,0-46,4%) presentó respuesta subóptima al tratamiento. Estos pacientes tenían una media de edad mayor, mayor proporción de mujeres y de pensionistas respecto al grupo de remisión, así como de comorbilidad. También peores porcentajes de cumplimiento (65,1 frente a 67,7%) y persistencia del tratamiento a los 12 meses (31,8 frente a 53,2%), respectivamente; p<0,001. Los costes sanitarios/anuales fueron de 826,1 € para pacientes con respuesta subóptima frente a 451,2 € en los pacientes en remisión; pérdidas de productividad de 1.842,0 frente a 991,4 €, respectivamente; p<0,001. Los factores asociados a la respuesta subóptima fueron: falta de cumplimiento (OR=1,7), años de enfermedad (OR=1,2), edad (OR=1,1) y presencia de comorbilidad (OR=1,1). Conclusiones: Los pacientes con respuesta subóptima al tratamiento AD inicial presentaron mayor comorbilidad, menor cumplimiento terapéutico y ocasionaron mayores costes totales, especialmente en pérdidas de productividad laboral(AU)

Objective: To evaluate the compliance, persistence and costs of the treatment of major depressive disorder (MDD) in the setting of Primary Care, placing emphasis on the different aspects of those patients with an initial suboptimal response to antidepressant treatment. Design: A retrospective observational study using the population registers of Badalona Healthcare Services. The inclusion criteria consisted of; age ≥18 years, initial episode during 2008-2009, and to be on antidepressant treatment for at least 8 weeks after the first prescription. The follow-up was 12 months. Two study groups were formed, patients with suboptimal response, and remission. Main measurements: Sociodemographic data, compliance and adherence to treatment, health costs (direct and indirect).ResultsA total of 2,260 subjects were analysed (mean age 58.8 years, 74% women). Just under half (42.7%, 95% CI; 40.0-46.4%) had a suboptimal response to the treatment. These patients had a higher mean age, a higher proportion of women, and pensioners, as well as higher comorbidity, compared to the remission group. They also had poorer compliance percentages (65.1% vs. 67.7%) and treatment persistence at 12 months (31.8% vs. 53.2%), respectively, P<0.001. The annual health costs were, 826.1€ for patients with a suboptimal response vs. 451.2€ in patients in remission; loss of productivity 1,842.0€ vs. 991.4€, respectively; P<0.001. The factors associated to a suboptimal response were; lack of compliance (OR=1.7), years with the disorder (OR=1.2), age (OR=1.1) and presence of comorbidity (OR=1.1). Conclusions: The patients with an initial suboptimal response to antidepressant treatment had a higher comorbidity, lower therapeutic compliance, and incurred higher total costs, particularly in losses in work productivity(AU)

Cataleptic postures in thalamic hemorrhage: case report

We report a case of catalepsy associated with thalamic hemorrhage. A 72 year-old hypertensive woman had acute onset of right-sided weakness and speech disturbances. She was on anticoagulants because of aortic valve replacement. When postures were imposed, the patient maintained the left upper limb raised for several minutes, even in uncomfortable or bizarre positions. A CT scan of the head revealed a left thalamic hemorrhage. Cataleptic postures have been reported in few cases with acute stroke