Delayed cognitive processing and treatment status quo bias in early-stage multiple sclerosis.

BACKGROUND: The evolving therapeutic landscape requires more participation of patients with relapsing remitting multiple sclerosis (RRMS) in treatment decisions. The aim of this study was to assess the association between patient's self-perception, cognitive impairment and behavioral factors in treatment choices in a cohort of patients at an early stage of RRMS. METHODS: We conducted a multicenter, non-interventional study including adult patients with a diagnosis of RRMS, a disease duration ≤18 months and receiving care at one of the 21 participating MS centers from across Spain. We used patient-reported measures to gather information on fatigue, mood, quality of life, and perception of severity of their MS. Functional metrics (Expanded Disability Status Scale [EDSS], cognitive function by the Symbol Digit Modalities Test [SDMT], 25-foot walk test) and clinical and radiological data were provided by the treating neurologist. The primary outcome of the study was status quo (SQ) bias, defined as participant's tendency to continue taking a previously selected but inferior treatment when intensification was warranted. SQ bias was assessed based on participants treatment preference in six simulated RRMS case scenarios with evidence of clinical relapses and radiological disease progression. RESULTS: Of 189 participants who met the inclusion criteria, 188 (99.5%) fully completed the study. The mean age was 36.6 ± 9.5 years, 70.7% female, mean disease duration: 1.2 ± 0.8 years, median EDSS score: 1.0 [IQR=0.0-2.0]). Overall, 43.1% patients (n = 81/188) had an abnormal SDMT (≤49 correct answers). SQ bias was observed in at least one case scenario in 72.3% (137/188). Participant's perception of their MS severity was associated with higher SQ bias (ß coeff 0.042; 95% CI 0.0074-0.076) among those with delayed cognitive processing. Higher baseline EDSS and number of T2 lesions were predictors of delayed processing speed (OR EDSS=1.57, 95% CI: 1.11-2.21, p = 0.011; OR T2 lesions=1.50, 95% CI: 1.11-2.03, p<0.01). Bayesian multilevel model accounting for clustering showed that delayed cognitive processing (exp coeff 1.06; 95% CI 1.04-1.09) and MS symptoms severity (exp coeff 1.28; 95% CI 1.22-1.33) were associated with SQ bias. CONCLUSION: Over 40% of patients in earlier stages of RRMS experience delays in cognitive processing that might affect their decision-making ability. Our findings suggest that patients' self-perception of disease severity combined with a delay in cognitive processing would affect treatment choices leading to status quo bias early in the course of their disease.

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.

Multiple sclerosis susceptibility genes: associations with relapse severity and recovery.

OBJECTIVE: Patients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack. METHODS: 503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack. RESULTS: The MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year. CONCLUSIONS: Some MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.

Association of multiple sclerosis susceptibility variants and early attack location in the CNS.

OBJECTIVE: The anatomic location of subsequent relapses in early multiple sclerosis (MS) appears to be predicted by the first attack location. We sought to determine if genetic polymorphisms associated with MS susceptibility are associated with attack location. METHODS: 17 genome-wide association study-identified MS susceptibility polymorphisms were genotyped in 503 white, non-Hispanic patients seen within a year of MS onset. Their association with the CNS location of the first two MS attacks was assessed in multivariate repeated measures analyses (generalized estimating equations with robust standard errors). RESULTS: The IL12A polymorphism was independently associated with increased odds of attacks involving the spinal cord (OR = 1.52, 95% CI 1.11, 2.07, p = 0.009), as was the IRF8 polymorphism (OR = 2.40, 95% CI [1.04, 5.50], p = 0.040). The IL7R polymorphism was associated with reduced odds of attacks involving the brainstem/cerebellum (OR = 0.46, 95% CI 0.22, 0.97, p = 0.041), as were the TNFRSF1A and IL12A polymorphisms. The CD6 polymorphism conferred reduced odds of optic neuritis as an attack location (OR = 0.69, 95% CI [0.49, 0.97], p = 0.034). Several other genes showed trends for association with attack location. CONCLUSIONS: Some of the MS susceptibility genes may be associated with MS attack location. The IL12A polymorphism is of particular interest given that interferon beta therapy appears to influence IL12 levels. These findings may lead to improved understanding of MS pathogenesis and treatment.

Cáncer primario de la trompa de falopio / Primary cancer of the fallopian tube

Se muestra un caso de una paciente de 42 años, la cual es laparotomizada de urgencia por presentar un abdomen agudo ginecológico, hallando: hemoperitoneo, tumor de ovario izquierdo con cápsula rota y sangrante y trompa izquierda dilatada. Se le realiza anexectomía izquierda siendo el informe anatomopatológico diferido: 1) tumor de células de la granulosa y 2) adenocarcinoma tubario pobremente diferenciado, estadio IA. Con este diagnóstico se decide reoperar a la paciente. Se realiza histerectomía total con anexectomía derecha y omentectomía. En la piez de resección no se halla tumor residual. De acuerdo con la literatura consultada se resuelve continuar con los controles periódicos dado que la radioterapía no mejoraría la sobrevida ni impediría las recidivas y la quimioterapía sería útil en estadios más avanzados. A 17 meses de la primera cirugía continúa sin evidencias de enfermedad. Se trae consideración esdte caso por lo infrecuente de cada una de las patologías y su rara concomitancia y se efectúa una revisión bibliográfica

Cáncer primario de la trompa de falopio / Primary cancer of the fallopian tube

Se muestra un caso de una paciente de 42 años, la cual es laparotomizada de urgencia por presentar un abdomen agudo ginecológico, hallando: hemoperitoneo, tumor de ovario izquierdo con cápsula rota y sangrante y trompa izquierda dilatada. Se le realiza anexectomía izquierda siendo el informe anatomopatológico diferido: 1) tumor de células de la granulosa y 2) adenocarcinoma tubario pobremente diferenciado, estadio IA. Con este diagnóstico se decide reoperar a la paciente. Se realiza histerectomía total con anexectomía derecha y omentectomía. En la piez de resección no se halla tumor residual. De acuerdo con la literatura consultada se resuelve continuar con los controles periódicos dado que la radioterapía no mejoraría la sobrevida ni impediría las recidivas y la quimioterapía sería útil en estadios más avanzados. A 17 meses de la primera cirugía continúa sin evidencias de enfermedad. Se trae consideración esdte caso por lo infrecuente de cada una de las patologías y su rara concomitancia y se efectúa una revisión bibliográfica