Dr Ruth Ann Marrie discusses the prevalence and effects of comorbidities in people living with multiple sclerosis.
Thanks so much for the opportunity to talk to you today about the effects of comorbidity in people living with My name is Ruth Ann Marrie. I’m a professor of medicine and community health and epidemiology, and the Multiple Sclerosis Clinical Research Chair at Dalhousie University.
Today, I’d like to talk to you about what comorbidities often affect people with MS, how often they occur, and the effects of comorbidity on MS-related outcomes. When we talk about comorbidity, we’re referring to the total burden of illness other than the specific disease of interest. In our case, MS is the disease of interest, so the comorbidities could includeWhy, more broadly, are we interested in studying comorbidity? Comorbidity may help us to better explain the difference in outcomes between people with MS; we know outcomes are highly. It may help us better prognosticate and make treatment decisions for people with MS. It may also give us insights into the pathogenesis of MS. If we found that diabetes was associated with worse outcomes, we might think about how diabetes affects the brain in terms of its effects on the endothelium, for example, or the role of insulin receptors, and that might then lead to new treatment avenues. What do we know about comorbidity in MS at the present time? We know it’s present throughout the disease course, and people with MS actually have aeven before they present with their first clinical symptoms. We’ve seen that people with MS have an increased incidence of), and anxiety disorders. Depending on the age of the individual with MS at the time of their initial presentation, theIf we take a random snapshot of any prevalent MS population, then the most common comorbidities we see are similar to those that we see at diagnosis, with depression and anxiety disorders as well as hypertension being prevalent. Hyperlipidemia and irritable bowel syndrome are also present. of people with MS are going to have depression or an anxiety disorder at any given point in their disease course. In contrast, conditions like hypertension, hyperlipidemia, and diabetes are going to increase in prevalence with age. This means people are typically going to have a much higher burden of comorbidity later in their disease course when it’s already becoming more difficult to manage their MS, and they may be taking many symptomatic therapies. in the time from symptom onset to diagnosis, the severity of disability at diagnosis, the rapidity of disability progression and lifespan, and quality of life. I’m going to focus on a couple of those for today — specifically, relapses and disability progression. — found that among individuals with psychiatric comorbidity, their disability progressed faster. She and, using these datasets, followed over 2000 people for an average of about 10 years. For people who had a mood or anxiety disorder, they accrued nearly 0.3 more Expanded Disability Status Scale point per year than people without psychiatric comorbidity. You might think, well, that’s not very much. When you consider that most people with a psychiatric disorder are going to face that long term, you think about that over a 10-year time horizon, that’s the difference of about 3 EDSS points. That’s the difference between mild and moderate disability, so it’s quite substantial. , who is based at UT Southwestern, and colleagues, using meta-analysis of clinical trial datasets. It included 17 trials involving almost 17,000 people with MS. The advantage of this dataset is that people in clinical trials are followed very closely and rigorously, with frequent assessments. She and her colleagues identified comorbidities at the time of enrollment in the clinical trials, and 61% of participants in the trials had some evidence of disease activity, whether it was relapses, disability worsening, or new lesions on MRI. Individuals who had three or more comorbidities had a 14% increased rate of disease activity. Having two or more cardiometabolic comorbidities was associated with a 21% increased rate of any disease activity. When they looked at individual comorbidities, they found that depression and ischemic heart disease seemed to be the biggest driver of those effects. This is really important to think about when you look specifically at relapses. More comorbidities were associated with more relapses. They also found that more comorbidities were associated with faster disability worsening. This really points to the adverse impact of comorbidity on outcomes in MS. This is an example of a longitudinal design, rigorously assessed, so it reduces concerns about the concept of reverse causality — that is, that people with more severe MS may be more likely to accrue comorbidities because they’re less physically active, they’re not able to eat as well, and so on. The design doesn’t fully mitigate that concern. , which tried to address this issue by using polygenic scores as an instrumental variable. Polygenic scores are basically weighted averages of all the variants that would be associated with a particular outcome — in this case, depression. The nice thing about using genes is that they are assigned to us at birth. MS couldn’t cause those genes to be assigned. If we can show that the polygenic score for depression is associated with relapses and disability progression in the same way that having depression is, then we can remove that concern about reverse causality. In fact, the study findings suggest that’s the case. When we put all of these kinds of findings together, they strongly suggest that there is an important role for comorbidities in influencing outcomes and that we really need to intensify our focus on preventing or mitigating those comorbidities as a means of improving outcomes in people with MS. A key question will be, “What’s the best way to do that?” Is it by simply treating these comorbidities the way we normally would, or do we need to treat them more aggressively? Does the type of intervention for those comorbidities matter in terms of achieving that goal of improving outcomes? I think we really need to begin to think about how to integrate these concepts into routine clinical practice. For that, guidelines and tools will be necessary to reach those goals.Editor’s Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication. Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see ourFast Five Quiz: How Do You Manage Multiple Sclerosis Symptoms? 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Multiple Sclerosis Center Of Excellence Multiple Sclerosis Multiple Sclerosis (MS) Disability Depression Anxiety Disorder Hypertension Anxiety Clinical Research Clinical Trials Clinical Studies Pre-Clinical Trial Double-Blind Study Double-Blind Studies Single-Blind Study Single-Blind Studies Cardiometabolic Risk Cardiometabolic Risk Factors
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