Disability Evolution in Multiple Sclerosis: How to Deal with Missing Transition Times in the Markov Model?

Petiot, V.; Quantin, Catherine; Teuff, Gwénaël Le; Chavance, Michel; Binquet, Christine; Abrahamowicz, Michał; Moreau, Thibault

doi:10.1159/000098518

Cited by 6 publications

(5 citation statements)

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“…There are many ways to model age-related cognitive changes, including Markov chains with Cox regression [18,19] logistic regression [20] , polytomous logistic regression [21,22] with adjustments for cofactors. These models, however, operate with a relatively small number of states ( !…”

Section: Discussionmentioning

confidence: 99%

Modeling the Impact of Sex on How Exercise Is Associated with Cognitive Changes and Death in Older Canadians

Fallah¹,

Mitnitski²,

Middleton³

et al. 2009

Neuroepidemiology

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Background: Exercise improves cognition and lessens the risk of death in older adults. Cognition and mortality are each also affected by biological sex, which might modify the effect of exercise. We investigated how sex mediates the impact of exercise on mortality and 5-year changes in cognition. Methods: In the Canadian Study of Health and Aging (n = 8,403, 60.7% women), cognitive states were defined as errors in the Modified Mini-Mental State Examination. Improvement and declines were modeled using a 4-parameter truncated Poisson distribution. Results: Men and women showed similar levels of improvement or stabilization (34.1%, 95% CI = 32.1–35.9 in women and 30.2%, 95% CI = 28.2–32.4 in men). In unadjusted analysis, more men died (34%, 95% CI = 32.3–36.3) than did women (30.3%, 95% CI = 28.4–32.2). Higher education was beneficial for cognitive function in both sexes, but did not impact survival when other factors were considered. The effect of exercise differed by sex: women had a survival advantage compared with men, but men most benefited in cognitive functioning. Conclusions: Exercise is strongly associated with cognitive improvement and stabilization in men, and with better survival in women. In contrast to conventional approaches, our model allows us to analyze how different risk factors affect cognition to any degree, and simultaneously to assess their impact on survival.

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Section: Discussionmentioning

confidence: 99%

Modeling the Impact of Sex on How Exercise Is Associated with Cognitive Changes and Death in Older Canadians

Fallah¹,

Mitnitski²,

Middleton³

et al. 2009

Neuroepidemiology

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“…A Markov model is a general MSM in which a system switches between different states assuming a certain transition probability. Multistate Markov models are commonly used in studies of chronic diseases, in which patients are assumed to pass through a series of discrete disease stages with 1 final state, either death or the terminal stage of a disease from which no exacerbation is possible, that is irreversible and referred to as an “absorbing” state . This approach works very well for censored data and has been implemented in the software solution R (R Statistical Foundation; add-on package msm) …”

Section: Methodsmentioning

confidence: 99%

“…Multistate Markov models are commonly used in studies of chronic diseases, in which patients are assumed to pass through a series of discrete disease stages with 1 final state, either death or the terminal stage of a disease from which no exacerbation is possible, that is irreversible and referred to as an "absorbing" state. 12,13 This approach works very well for censored data 14 and has been implemented in the software solution R (R Statistical Foundation; add-on package msm). 15 With the addition of a dropout state, ie, treatment cessation for any reason including mortality, as an absorbing state, our data reflected a 7-state system: 6 vision states as well as 1 absorbing health state in which patients were no longer treated.…”

Section: Statistical Analysesmentioning

confidence: 99%

Lifetime Outcomes of Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration

et al. 2020

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he late-stage neovascular form of age-related macular degeneration (nAMD) is the largest single cause of irreversible, severe vision loss in all high-income countries, causing estimated direct costs of more than €50 billion (US $59 billion) in the EU alone each year. 1,2 Current treatment options that preserve sight and lead to a considerable improvement in some patients are based on the inhibition of vascular endothelial growth factor (anti-VEGF) and are delivered as regular intravitreal injections. 3 In contrast, nonintervention outcomes lead to legal blindness within 3 years following onset in 80% of patients affected. 4 Because anti-VEGF treatment does not cure nAMD but only controls it, treatment is for the long term and is often required until either the eye worsens to levels where treatment is no longer considered beneficial or the patient dies.However, to date, only a few reports on real-world outcomes beyond 5 years are available, and attrition is high, as is inevitable in long-term observational studies in elderly populations. 5,6 Thus, we do not know whether and for how long patients retain useful visual acuity (VA) that allows them to continue to undertake activities that were often lost prior to the advent of anti-VEGF treatment, such as reading and driving. Considering the considerable societal effects of both nAMD and its treatment in terms of costs, a better understanding of lifetime outcomes of anti-VEGF treatment for nAMD is required. Long-term treatment outcomes or prognosis can be estimated using multistate models (MSMs), which capture transition between different health states over time conditional on specific transition probabilities based on real-world data. 7 In this study, we used MSMs as well as data from patients with long-term, ongoing anti-VEGF treatment for nAMD in routine IMPORTANCE Neovascular age-related macular degeneration (nAMD), the largest single cause of irreversible severe vision loss in high-income countries, can now be treated with vascular endothelial growth factor (VEGF) inhibitors, but to our knowledge, no data on lifetime outcomes are available.OBJECTIVE To determine visual acuity (VA) outcomes of anti-VEGF treatment for nAMD in both eyes for patients' remaining lifetime.DESIGN, SETTING, AND PARTICIPANTS Multistate modeling using real-world cohort data of 3192 patients with nAMD (>67 000 visits) treated in routine eye clinics in Australia, New Zealand, and Switzerland. Data were analyzed between 2007 and 2015.EXPOSURES Intravitreal anti-VEGF treatment at the treating physician's discretion and prospective data collection in standardized registry. MAIN OUTCOMES AND MEASURESVisual acuity in both eyes over the remaining lifetime. RESULTSFor the mean remaining lifetime of 11 years, an estimated 12% (n = 371; 95% CI, 345-400) of the sample retained driving VA and an estimated 15% (n = 463; 95% CI, 434-495) reading VA in at least 1 eye. At that time, an estimated 82% of the sample (n = 2629; 95% CI, 2590-2660) had dropped out. Younger age at baseline and more injections dur...

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“…Progression is characterized by a 6-month period of continuous deterioration in neurological status, while relapse is defined as the occurrence or aggravation of neurological symptoms lasting for more than 24 h (23,24). These attacks should be separated by at least 30 days in order to be considered a relapse.…”

Section: Clinical Characteristics: Children Versus Adultsmentioning

confidence: 99%

Multiple Sclerosis Therapies in Pediatric Patients: Challenges and Opportunities

Jančić

Nikolić

Ivančević

et al. 2017

Multiple Sclerosis: Perspectives in Treatment and Pathogenesis

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Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). The etiology of MS is most likely multifactorial; it is dependent on genetic, autoimmune, and environmental factors, with a variable course among patients. The two main clinical events that characterize MS are relapses and progression. In recent years, diagnosis and treatment of pediatric MS has drawn attention of the scientific community. Management of pediatric MS focuses on reducing relapses and symptoms via administration of disease-modifying drugs (DMDs) and specific symptomatic treatment. A multidisciplinary approach to pediatric MS treatment is preferred, which aims at alleviating and preventing the accumulation of neurological deficits. MS therapy should be based on DMDs, that is, immunomodulatory drugs. These drugs, which sequester immune system activity, are further subdivided into two categories: first-line and second-line immunomodulatory therapy. First-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, Multiple Sclerosis in Pediatric Patients 40and glatiramer acetate) is ineffective (either no response or partial response) in roughly 30% of patients. Patients with a poor response to first-line therapy require second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab, alemtuzumab, and ocrelizumab). In addition to immunomodulatory drugs, treatment of relapses also involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis.

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Disability Evolution in Multiple Sclerosis: How to Deal with Missing Transition Times in the Markov Model?

Cited by 6 publications

References 70 publications

Modeling the Impact of Sex on How Exercise Is Associated with Cognitive Changes and Death in Older Canadians

Modeling the Impact of Sex on How Exercise Is Associated with Cognitive Changes and Death in Older Canadians

Lifetime Outcomes of Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration

Multiple Sclerosis Therapies in Pediatric Patients: Challenges and Opportunities

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