Comorbidity delays diagnosis and increases disability at diagnosis in MS
Open accessAbstract
BACKGROUND: Comorbidity is common in the general population and is associated with adverse health outcomes. In multiple sclerosis (MS), it is unknown whether preexisting comorbidity affects the delay between initial symptom onset and diagnosis ("diagnostic delay") or the severity of disability at MS diagnosis. OBJECTIVES: Using the North American Research Committee on Multiple Sclerosis Registry, we assessed the association between comorbidity and both the diagnostic delay and severity of disability at diagnosis. In 2006, we queried participants regarding physical and mental comorbidities, including date of diagnosis, smoking status, current height, and past and present weight. Using multivariate Cox regression, we compared the diagnostic delay between participants with and without comorbidity at diagnosis. We classified participants enrolled within 2 years of diagnosis (n = 2,375) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with comorbidity using polytomous logistic regression. RESULTS: The study included 8,983 participants. After multivariable adjustment for demographic and clinical characteristics, the diagnostic delay increased if obesity, smoking, or physical or mental comorbidities were present. Among participants enrolled within 2 years of diagnosis, the adjusted odds of moderate as compared to mild disability at diagnosis increased in participants with vascular comorbidity (odds ratio [OR] 1.51, 95% CI 1.12-2.05) or obesity (OR 1.38, 95% CI 1.02-1.87). The odds of severe as compared with mild disability increased with musculoskeletal (OR 1.81, 95% CI 1.25-2.63) or mental (OR 1.62, 95% CI 1.23-2.14) comorbidity. CONCLUSIONS: Both diagnostic delay and disability at diagnosis are influenced by comorbidity. The mechanisms underlying these associations deserve further investigation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a study of comorbidity in MS, 668 patients who also self-reported mental comorbidities experienced a delay to diagnosis of MS and were more likely to have severe, rather than mild, disability two years after diagnosis.
“A study of comorbidity in patients with MS found that the 668 patients who also self-reported mental comorbidities experienced a delay to diagnosis of MS, and were more likely to have severe, rather than mild, disability two years after diagnosis [54].”
From Functional neurological disorder and multiple sclerosis: a systematic review of misdiagnosis and clinical overlap (2022) · cites this paper as [54]
The Results identify 668 participants with self-reported mental comorbidities, and the Abstract reports both increased diagnostic delay with mental comorbidity and higher odds of severe rather than mild disability. But disability was assessed at diagnosis among participants enrolled within two years of diagnosis—not two years after diagnosis. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 37 · Cited by 276
Research works printed but not linked: 34
- Hoffman C, Rice D, Sung HY. Persons with chronic condit- ions: their prevalence and costs. JAMA 1996;276:1473- 1479.
- Braunstein JB, Anderson GF, Gerstenblith G, et al. Non- cardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure. J Am Coll Cardiol 2003;42:1226-1233.
- Dunlop DD, Manheim LM, Sohn MW, Liu X, Chang RW. Incidence of functional limitation in older adults: the impact of gender, race, and chronic conditions. Arch Phys Med Rehabil 2002;83:964-971.
- Gijsen R, Hoeymans N, Schellevis FG, Ruwaard D, Satari- ano WA, van den Bos GA. Causes and consequences of co- morbidity: a review. J Clin Epidemiol 2001;54:661-674.
- Fleming ST, Pursley HG, Newman B, Pavlov D, Chen K. Comorbidity as a predictor of stage of illness for patients with breast cancer. Med Care 2005;43:132-140.
- Macdonald S, Macleod U, Campbell N, Weller D, Mitchell E. Systematic review of factors influencing patient and practi- tioner delay in diagnosis of upper gastrointestinal cancer. Br J Cancer 2006;94:1272-1280.
- Marrie RA, Horwitz RI, Cutter G, Tyry T, Campagnolo D, Vollmer T. Comorbidity, socioeconomic status, and multiple sclerosis. Mult Scler 2008;14:1091-1098.
- Bergamaschi R, Berzuini C, Romani A, Cosi V. Predicting secondary progression in relapsing-remitting multiple scle- rosis: a Bayesian analysis. J Neurol Sci 2001;189:13-21.
- Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study, 3: multivariate anal- ysis of predictive factors and models of outcome. Brain 1991;114:1045-1056.
- Katz JN, Chang LC, Sangha O, Fossel AH, Bates DW. Can comorbidity be measured by questionnaire rather than medical record review? Med Care 1996;34:73-84.
- Okura Y, Urban LH, Mahoney DW, Jacobsen SJ, Rode- heffer RJ. Agreement between self-report questionnaires and medical record data was substantial for diabetes, hy- pertension, myocardial infarction and stroke but not for heart failure. J Clin Epidemiol 2004;57:1096-1103.
- Polliack ML, Barak Y, Achiron A. Late-onset multiple scle- rosis. J Am Geriatr Soc 2001;49:168-171.
- Gusev E, Boiko A, Bikova O, et al. The natural history of early onset multiple sclerosis: comparison of data from Moscow and Vancouver. Clin Neurol Neurosurg 2002; 104:203-207.
- Marrie RA, Cutter G, Tyry T, Hadjimichael O, Campag- nolo D, Vollmer T. Changes in the ascertainment of mul- tiple sclerosis. Neurology 2005;65:1066-1070.
- Esbjerg S, Keiding N, Koch-Henriksen N. Reporting delay and corrected incidence of multiple sclerosis. Stat Med 1999;18:1691-1706.
- Kleinbaum DG, Klein M. Survival Analysis: A Self- Learning Text. New York: Springer-Verlag, 1997.
- Hohol MJ, Orav EJ, Weiner HL. Disease steps in mul- tiple sclerosis: a longitudinal study comparing disease steps and EDSS to evaluate disease progression. Mult Scler 1999;5:349-354.
- Marrie RA, Cutter G, Tyry T, Vollmer T, Campagnolo D. Does multiple sclerosis-associated disability differ between races? Neurology 2006;66:1235-1240.
- Agresti A. An Introduction to Categorical Data Analysis. New York: John Wiley & Sons, 1996.
- Shishehbor MH, Litaker D, Pothier CE, Lauer MS. Asso- ciation of socioeconomic status with functional capacity, heart rate recovery, and all-cause mortality. JAMA 2006; 295:784-792.
- Bjerager M, Palshof T, Dahl R, Vedsted P, Olesen F. De- lay in diagnosis of lung cancer in clinical practice. Br J Gen Pract 2006;56:863-868.
- Kirby S, Brown MG, Murray TJ, et al. Progression of mul- tiple sclerosis in patients with other autoimmune diseases. Mult Scler 2005;11:S28-S29.
- Hernan MA, Jick SS, Logroscino G, Olek MJ, Ascherio A, Jick H. Cigarette smoking and the progression of multiple sclerosis. Brain 2005;128:1461-1465.
- Koch M, van Harten A, Uyttenboogaart M, De Keyser J. Cigarette smoking and progression in multiple sclerosis. Neurology 2007;69:1515-1520.
- Jefferson AL, Massaro JM, Wolf PA, et al. Inflammatory biomarkers are associated with total brain volume: the Fra- mingham Heart Study. Neurology 2007;68:1032-1038.
- Fried LP, Bandeen-Roche K, Kasper JD, Guralnik JM. Association of comorbidity with disability in older women: the Women's Health and Aging Study. J Clin Epidemiol 1999;52:27-37.
- Rijken M, van Kerkhof M, Dekker J, Schellevis FG. Co- morbidity of chronic diseases: effects of disease pairs on physical and mental functioning. Qual Life Res 2005;14: 45-55.
- Kalsekar ID, Madhavan SS, Amonkar MM, et al. Impact of depression on utilization patterns of oral hypoglycemic agents in patients newly diagnosed with type 2 diabetes mellitus: a retrospective cohort analysis. Clin Ther 2006;28:306-318.
- Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Compari- son of drug adherence rates among patients with seven differ- ent medical conditions. Pharmacotherapy 2008;28:437-443.
- Turner BJ, Hollenbeak CS, Weiner M, Ten Have T, Tang SSK. Effect of unrelated comorbid conditions on hyperten- sion management. Ann Intern Med 2008;148:578-586.
- Berlowitz DR, Ash AS, Hickey EC, Glickman M, Fried- man R, Kader B. Hypertension management in patients- with diabetes: the need for more aggressive therapy. Diabe- tes Care 2003;26:355-359.
- Bakris GL, Weir MR, Shanifar S, et al. Effects of blood pressure level on progression of diabetic nephropathy: re- sults from the RENAAL study. Arch Intern Med 2003; 163:1555-1565.
- Ratzker PK, Feldman JM, Scheinberg LC, et al. Self- assessment of neurologic impairment in multiple sclerosis. J Neurol Rehabil 1997;11:207-211.
- Marrie RA, Goldman MD. Validity of performance scales for disability assessment in multiple sclerosis. Mult Scler 2007;13:1176-1182.
- Authors
- Marrie, R. A., Horwitz, R., Cutter, G., Tyry, T., Campagnolo, D., & Vollmer, T.
- Affiliations
- Barrow Neurological Institute (US)
- Corresponding author
- Marrie, R. A.
- Venue
- Neurology
- Published
- 2009-01-13
- Volume
- 72
- Issue
- 2
- Pages
- 117-124
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2677495
- OpenAlex
- W2163182789
- Cited by
- 276
- References
- 37
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 20 · 2023: 19 · 2022: 14 · 2021: 21 · 2020: 23 · 2019: 18 · 2018: 15 · 2017: 15 · 2016: 19 · 2015: 10 · 2014: 12 · 2013: 12 · 2012: 7
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society
- National Institutes of Health
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD04909)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Keywords
- multiple sclerosis, comorbidities, delayed diagnosis, obesity, smoking, psychiatric comorbidity, musculoskeletal comorbidities, vascular comorbidities, somatic comorbidity, disability severity
- MeSH terms
- Adult, Aged, Mental Disorders, Cerebrovascular Disorders, Diagnostic Errors, Disability Evaluation, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Musculoskeletal Diseases, Surveys and Questionnaires, Severity of Illness Index, Time Factors, Cohort Studies, Comorbidity, Prevalence, Logistic Models, Age of Onset, Early Diagnosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review