Comorbidity delays diagnosis and increases disability at diagnosis in MS

Marrie, Ruth Ann; Horwitz, Ralph I.; Cutter, Gary; Tyry, Tuula; Campagnolo, Denise I.; Vollmer, Timothy

doi:10.1212/01.wnl.0000333252.78173.5f

Cited by 222 publications

(181 citation statements)

References 34 publications

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“…Mortality from infectious diseases and diseases of the respiratory system was higher in the MS population than in the control population. These findings extend the results of previous studies that reported an effect of comorbidity on the diagnosis of and disability in MS 9 , suggesting that treatment and prevention of comorbidities improves survival in MS. Future research will fill important gaps in our knowledge about the worldwide epidemiology of comorbidity in MS 10 .…”

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confidence: 89%

Managing the complexity of multiple sclerosis

Ciccarelli

Thompson

2016

Nat Rev Neurol

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The application of imaging biomarkers has provided new insights into the mechanisms of damage in multiple sclerosis (MS) and the risk of MS development and progression. The goal of eliminating all disease activity requires a timely escalation of treatment. This increasing complexity is compounded by the need to treat comorbidities.Multiple sclerosis (MS) is an increasingly complex disease in terms of its pathogenesis, comorbidities, prognosis and treatment, and successful patient management requires knowledge of this complexity. In 2015, there have been advances in our understanding of the mechanisms of the disease, ways in which to formulate patient prognoses, how best to escalate treatment escalation, and the role of comorbidities. All of these aspects need to be incorporated into an effective management plan (Fig. 1).The mechanisms that underlie the pathogenesis of MS are yet to be fully elucidated, but they are known to include a cascade of events that induce physical and cognitive deficits. A reduction in neuronal integrity and function that affects the grey matter compartment is thought to be the key pathological process that leads to cognitive impairment in MS. However, findings of a study published by Freeman et al. 1 in 2015 suggest that synaptic and/or dendritic damage occurs prior to quantifiable grey matter volume loss, and might reflect neuronal and axonal loss that contributes to clinical deficits.In this study, Freeman et al. 1 used [ 11 C]flumazenil ([ 11 C]FMZ) PET, which quantifies GABAA receptor density in vivo, to identify grey matter damage beyond cortical lesions 2 . FMZ is an antagonist of the central benzodiazepine receptor, a component of the GABAA receptor complex that is present on axosomatic and axodendritic synapses throughout the cortical and subcortical grey matter. The number of [ 11 C]FMZ binding sites per grey matter region was lower in several cortical areas (the parietal, cingulate, and insular cortices and the left frontal cortex) and subcortical regions (the thalamus, hippocampus and amygdala) in patients with MS than in healthy controls. Greater amounts of neuronal damage were seen in patients with secondary-progressive MS than in patients with relapsing-remitting MS (RRMS), but the most striking result was that [ 11 C]FMZ binding was lower in patients with RRMS than in healthy controls, even in the absence of significant grey matter atrophy. A significant relationship was found between the level of cortical [ 11 C]FMZ binding and performance on several cognitive tests. A goal of future research is to provide neuroprotective and reparative therapies that could be applied at such early stages of MS to stop or at least slow down neurodegeneration and reduce cognitive impairment in progressive MS 3 .Clinically isolated syndromes (CIS) represent a patient's first neurological episode that is suggestive of MS. Most patients with CIS develop RRMS within 5 years of onset, and most patients with MS develop progressive MS 10-15 years after onset of MS. Although challenging, formulat...

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confidence: 89%

Managing the complexity of multiple sclerosis

Ciccarelli

Thompson

2016

Nat Rev Neurol

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“…2 Comorbidity is associated with longer diagnostic delays and greater disability at diagnosis and lower quality of life in MS. 3,4 The impact of comorbidity on health care utilization in MS is unknown, but is identified as a key knowledge gap for clinicians and decision-makers.…”

Section: Discussionmentioning

confidence: 99%

“…Physical comorbidities, such as hypertension, affect more than one-third of persons with MS. 1 Psychiatric comorbidities, such as depression, affect more than 50% of persons with MS over their lifetime. 2 Comorbidity is associated with longer diagnostic delays and greater disability at diagnosis and lower quality of life in MS. 3,4 The impact of comorbidity on health care utilization in MS is unknown, but is identified as a key knowledge gap for clinicians and decision-makers. 5 Health care utilization is high in the MS population, 6 with up to 25.8% of the MS population being hospitalized annually, 7 exceeding the rate of hospitalizations in the general population.…”

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confidence: 99%

Comorbidity increases the risk of hospitalizations in multiple sclerosis

et al. 2015

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Objective: We aimed to evaluate the association between comorbidity and rates of hospitalization in the multiple sclerosis (MS) population as compared to a matched cohort from the general population.Methods: Using population-based administrative data from the Canadian province of Manitoba, we identified 4,875 persons with MS and a matched general population cohort of 24,533 persons. We identified all acute care hospitalizations in the period 2007-2011. Using general linear models, we evaluated the association between comorbidity status and hospitalization rates (all-cause, non-MS-related, MS-related) in the 2 populations, adjusting for age, sex, and socioeconomic status.Results: Comorbidity was common in both cohorts. Over the 5-year study period, the MS population had a 1.5-fold higher hospitalization rate (adjusted rate ratio [aRR] 1.56; 95% confidence interval [CI] 1.44-1.68) than the matched population. Any comorbidity was associated with a 2-fold increased risk of non-MS-related hospitalization rates (aRR 2.21; 95% CI 1.73-2.82) in the MS population, but a nearly 4-fold increase in hospitalization rates in the matched population (aRR 3.85; 95% CI 3.40-4.35). Comorbidity was not associated with rates of hospitalization for MS-related reasons, regardless of how comorbidity status was defined. Conclusions:In the MS population, comorbidity is associated with an increased risk of all-cause hospitalizations, suggesting that the prevention and management of comorbidity may reduce hospitalizations. Neurology ® 2015;84:350-358 GLOSSARY aRR 5 adjusted rate ratio; CI 5 confidence interval; ICD-9 5 International Classification of Diseases-9; MS 5 multiple sclerosis; PHIN 5 personal health identification number; RR 5 rate ratio; SES 5 socioeconomic status.Comorbidity is common in the multiple sclerosis (MS) population. Physical comorbidities, such as hypertension, affect more than one-third of persons with MS.1 Psychiatric comorbidities, such as depression, affect more than 50% of persons with MS over their lifetime.2 Comorbidity is associated with longer diagnostic delays and greater disability at diagnosis and lower quality of life in MS. 3,4 The impact of comorbidity on health care utilization in MS is unknown, but is identified as a key knowledge gap for clinicians and decision-makers.5 Health care utilization is high in the MS population, 6 with up to 25.8% of the MS population being hospitalized annually, 7 exceeding the rate of hospitalizations in the general population. 8 The mean number of physician visits per year is also higher in the MS population.9 In other diseases, persons with multiple chronic health conditions have higher rates of health care utilization than persons with a single condition. 10Hospitalizations constitute the largest component of resource use in Canada and other industrialized countries, 11 and costs of hospitalizations for MS are rising. 12 In other chronic diseases, comorbidity is often undertreated, 13 potentially leading to increased hospitalizations. Therefore, we aimed to e...

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“…1 Therefore, the distinction between disease subtypes should be considered when analyzing MS as a timevarying covariate. It would be also reasonable to take into account the divergence between MS onset and MS diagnosis in time given that comorbidity delays the diagnosis of MS. 9 If it would be feasible to determine the average delay to diagnosis for the MS population, a sensitivity analysis testing whether adding that variable into the equation would influence the results could be helpful.…”

Section: Methodsmentioning

confidence: 99%

Journal Club: Effect of comorbidity on mortality in multiple sclerosis

Karamyan¹,

Sellner²

2016

Neurology

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Journal Club: Effect of comorbidity on mortality in multiple sclerosisMultiple sclerosis (MS) is a chronic demyelinating disease of the CNS estimated to reduce life expectancy by 7-14 years compared to demographically similar groups in the general population.1 While several disease complications pose a potential risk for mortality, results from large observational studies suggest that comorbidities substantially influence survival in MS. 2,3 In a recent Neurology ® article, Marrie et al. 4 applied an effective methodologic approach to assess the contribution of comorbidity to excess mortality in the MS population. Besides its considerable epidemiologic merit, the study has important implications for the management of patients with MS, particularly if closer surveillance and targeted interventions may reduce the burden of comorbidity among them and improve survival. performed a retrospective matched cohort study using population-based administrative data. The authors stratified cohorts by birth year in order to study temporal changes in survival, hypothesizing that the latter improves in the MS population over time. They also hypothesized that comorbidity shortens the survival of persons with MS. Cox regression analysis employed for statistical analysis provides us with a thorough insight into the effect of multiple covariates on the time to death, whereas some other studies traditionally use logistic regression, which estimates the probability of binary survival response (died vs alive) over the period of observation. An alternative method with time-to-event outcome is the log-rank test, which does not allow adjustment for confounding factors. 5METHODS The authors combined data extracted from 2 data sources. The first was administrative (health) data from the province of Manitoba, Canada, covering 98% of the population. The second data source was the Manitoba Vital Statistics Death Database, encompassing information on all deaths in Manitoba, including date and cause of death classified according to ICD-9 or ICD-10, depending on the time period. Using a validated administrative case definition, the authors identified all MS cases and up to 5 controls for each case, matched on sex, exact year of birth, and region of residence, from April 1, 1984, to March 31, 2012 To analyze the survival in both populations, the authors used univariate Cox regression with age as the time scale. Unlike the standard approach of using time on study as the time scale in a Cox regression (which means estimating time from entry into the study until the event of interest, typically death), and adjusting the model for age, this alternative approach to use age as the time scale allows a straightforward adjustment for multiple effects of aging process, and is recommended for analyzing epidemiologic cohort data. 6 On the other hand, the authors addressed a common source of bias in applications of survival analysis known as left truncation, which occurs when the individuals who have already passed the event of interest prior to study...

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Comorbidity delays diagnosis and increases disability at diagnosis in MS

Abstract: Both diagnostic delay and disability at diagnosis are influenced by comorbidity. The mechanisms underlying these associations deserve further investigation.

Cited by 222 publications

References 34 publications

Managing the complexity of multiple sclerosis

Managing the complexity of multiple sclerosis

Comorbidity increases the risk of hospitalizations in multiple sclerosis

Journal Club: Effect of comorbidity on mortality in multiple sclerosis

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