Recommendations for observational studies of comorbidity in multiple sclerosis

Objective: To reach consensus about the most relevant comorbidities to study in multiple sclerosis (MS) with respect to incidence, prevalence, and effect on outcomes; review datasets that may support studies of comorbidity in MS; and identify MS outcomes that should be prioritized in such studies. Methods: We held an international workshop to meet these objectives, informed by a systematic review of the incidence and prevalence of comorbidity in MS, and an international survey regarding research priorities for comorbidity. Results: We recommend establishing age- and sex-specific incidence and prevalence estimates for 5 comorbidities (depression, anxiety, hypertension, hyperlipidemia, and diabetes); evaluating the effect of 7 comorbidities (depression, anxiety, hypertension, diabetes, hyperlipidemia, chronic lung disease, and autoimmune diseases) on disability, quality of life, brain atrophy and other imaging parameters, health care utilization, employment, and mortality, including age, sex, race/ethnicity, socioeconomic status, and disease duration as potential confounders; harmonizing study designs across jurisdictions; and conducting such studies worldwide. Ultimately, clinical trials of treating comorbidity in MS are needed. Conclusion: Our recommendations will help address knowledge gaps regarding the incidence, prevalence, and effect of comorbidity on outcomes in MS

A Practical, Global Perspective on Using Administrative Data to Conduct Intensive Care Unit Research

Various data sources can be used to conduct research on critical illness and intensive care unit (ICU) use. Most published studies derive from randomized controlled trials, large-scale clinical databases, or retrospective chart reviews. However, few investigators have access to such data sources or possess the resources to create them. Hospital administrative data, also called health claims data, constitute an important alternative data source that can be used to address a broad range of research questions, including many that would be difficult to study in interventional studies. Such data often contain information that allows identification of ICU care, specific types of critical illness, and ICU-related procedures. The strengths of using administrative databases are that many are population-based, cover broad geographic regions, and are large enough to provide high statistical power and precise effect estimates. Linking hospital data to other databases regarding chronic care facilities, home care services, or rehabilitation services, for example, can expand the scope of research questions that can be answered. However, the limitations of administrative data must be recognized. They are not collected for research purposes; thus, data elements may vary in accuracy, and key clinical variables such as ICU-specific physiologic and laboratory data are usually lacking. Specific efforts should be made to validate the data elements used, as has been done in several world regions. As with any other research question, it is imperative that the analysis plan be carefully defined in advance and that appropriate attention be paid to potential sources of bias and confounding

A systematic review of the incidence and prevalence of sleep disorders and seizure disorders in multiple sclerosis

Background: Several studies have suggested that comorbid neurologic disorders are more common than expected in multiple sclerosis (MS). Objective: To estimate the incidence and prevalence of comorbid seizure disorders and sleep disorders in persons with MS and to evaluate the quality of studies included. Methods: The PUBMED, EMBASE, Web of Knowledge, and SCOPUS databases, conference proceedings, and reference lists of retrieved articles were searched. Two reviewers independently screened abstracts to identify relevant articles, followed by full-text review of selected articles. We assessed included studies qualitatively and quantitatively (I2 statistic), and conducted meta-analyses among population-based studies. Results: We reviewed 32 studies regarding seizure disorders. Among population-based studies the incidence of seizure disorders was 2.28% (95% CI: 1.11–3.44%), while the prevalence was 3.09% (95% CI: 2.01–4.16%). For sleep disorders we evaluated 18 studies; none were population-based. The prevalence ranged from 0–1.6% for narcolepsy, 14.4–57.5% for restless legs syndrome, 2.22–3.2% for REM behavior disorder, and 7.14–58.1% for obstructive sleep apnea. Conclusion: This review suggests that seizure disorders and sleep disorders are common in MS, but highlights gaps in the epidemiological knowledge of these conditions in MS worldwide. Other than centralwestern Europe and North America, most regions are understudied

The incidence and prevalence of psychiatric disorders in multiple sclerosis:a systematic review

Background: Psychiatric comorbidity is associated with lower quality of life, more fatigue, and reduced adherence to disease-modifying therapy in multiple sclerosis (MS). Objectives: The objectives of this review are to estimate the incidence and prevalence of selected comorbid psychiatric disorders in MS and evaluate the quality of included studies. Methods: We searched the PubMed, PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of retrieved articles. Abstracts were screened for relevance by two independent reviewers, followed by full-text review. Data were abstracted by one reviewer, and verified by a second reviewer. Study quality was evaluated using a standardized tool. For population-based studies we assessed heterogeneity quantitatively using the I2 statistic, and conducted meta-analyses. Results: We included 118 studies in this review. Among population-based studies, the prevalence of anxiety was 21.9% (95% CI: 8.765.0%), while it was 14.8% for alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.40.0%) for depression, 2.5% for substance abuse, and 4.3% (95% CI: 0.3%) for psychosis. Conclusion: This review confirms that psychiatric comorbidity, particularly depression and anxiety, is common in MS. However, the incidence of psychiatric comorbidity remains understudied. Future comparisons across studies would be enhanced by developing a consistent approach to measuring psychiatric comorbidity, and reporting of age-, sex-, and ethnicity-specific estimates

A systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis

Background: Findings regarding the prevalence of vascular comorbidities in multiple sclerosis (MS) are conflicting.Objective: The objective of this review is to estimate the incidence and prevalence of vascular comorbidities and predisposing comorbidities in persons with MS and to assess the quality of the included studies.Methods: The PubMed, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched. One reviewer abstracted data using a standardized data collection form, while the second reviewer verified the abstraction. Included studies were assessed qualitatively. Quantitatively, we assessed studies using the I 2 statistic, and conducted meta-analyses for population-based studies only.Results: The prevalence of hypertension and hyperlipidemia exceeded 10% in the MS population and increased with age. While the prevalence of ischemic heart disease, congestive heart failure, and stroke were less than 5% overall, the prevalence of these conditions exceeded expectations when compared to the general population. Cardiac valvular disease, however, affected the MS population less often than expected. Problems with study quality were common.Conclusion: Despite the relatively high prevalence of some vascular comorbidities in the MS population, important gaps exist in our understanding of their epidemiology. Most of our knowledge is based on studies conducted in a small number of regions

A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: Overview

Background: Comorbidity is an area of increasing interest in multiple sclerosis (MS). Objective: The objective of this review is to estimate the incidence and prevalence of comorbidity in people with MS and assess the quality of included studies. Methods: We searched the PubMed, SCOPUS, EMBASE and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles. Two reviewers independently screened abstracts. One reviewer abstracted data using a standardized form and the abstraction was verified by a second reviewer. We assessed study quality using a standardized approach. We quantitatively assessed population-based studies using the I2 statistic, and conducted random-effects meta-analyses. Results: We included 249 articles. Study designs were variable with respect to source populations, case definitions, methods of ascertainment and approaches to reporting findings. Prevalence was reported more frequently than incidence; estimates for prevalence and incidence varied substantially for all conditions. Heterogeneity was high. Conclusion: This review highlights substantial gaps in the epidemiological knowledge of comorbidity in MS worldwide. Little is known about comorbidity in Central or South America, Asia or Africa. Findings in North America and Europe are inconsistent. Future studies should report age-, sex- and ethnicityspecific estimates of incidence and prevalence, and standardize findings to a common population

A systematic review of the incidence and prevalence of cancer in multiple sclerosis

Background: Studies of cancer incidence and prevalence in multiple sclerosis (MS) have produced conflicting results. Objective: To estimate the incidence and prevalence of cancer in persons with MS and review the quality of included studies. Methods: We searched the PUBMED, SCOPUS, Web of Knowledge, and EMBASE databases, conference proceedings, and reference lists of all articles retrieved. Abstracts were screened for relevance by two reviewers. Data from included articles were captured using a standardized form, and the abstraction was verified by a second reviewer. We assessed quality of the included studies. We quantitatively assessed studies using the I2 statistic, and conducted meta-analyses for population-based studies. Results: We identified 38 studies. Estimates for incidence and prevalence varied substantially for most cancers. In population-based studies, cervical, breast, and digestive cancers had the highest incidence. The risk of meningiomas and urinary system cancers appeared higher than expected, while the risks of pancreatic, ovarian, prostate and testicular cancer were lower than expected. Conclusion: The complexity of understanding cancer risk in MS is augmented by inconsistencies in study design, and the relative paucity of age, sex and ethnicity-specific risk estimates from which the strong impact of age on the incidence of cancers can be assessed

A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis

Background: As new therapies emerge which increase the risk of autoimmune disease it is increasingly important to understand the incidence of autoimmune disease in multiple sclerosis (MS). Objective: The purpose of this review is to estimate the incidence and prevalence of comorbid autoimmune disease in MS. Methods: The PUBMED, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched, and abstracts were independently screened by two reviewers. The data were abstracted by one reviewer using a standardized data collection form, and the findings were verified by a second reviewer. We assessed quality of the included studies using a standardized approach and conducted meta-analyses of population-based studies. Results: Sixty-one articles met the inclusion criteria. We observed substantial heterogeneity with respect to the populations studied, methods of ascertaining comorbidity, and reporting of findings. Based solely on population-based studies, the most prevalent autoimmune comorbidities were psoriasis (7.74%) and thyroid disease (6.44%). Our findings also suggest an increased risk of inflammatory bowel disease, likely uveitis and possibly pemphigoid. Conclusion: Fewer than half of the studies identified were of high quality. Population-based studies that report age, sex and ethnicity-specific estimates of incidence and prevalence are needed in jurisdictions worldwide

The incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in multiple sclerosis: A systematic review

Background: As new disease-modifying therapies emerge a better knowledge of the risk of comorbid disease in multiple sclerosis (MS) is needed. Objective: To estimate the incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in MS. Methods: We systematically reviewed the world literature by searching PUBMED, EMBASE, SCOPUS, the Web of Knowledge, and reference lists of retrieved articles. For selected articles, one reviewer abstracted data using a standardized form. The abstraction was verified by a second reviewer. The quality of all selected studies was assessed. For population-based studies we quantitatively assessed studies using the I2 statistic, and conducted random effects meta-analyses. Results: Study designs were heterogeneous with respect to populations, case definitions, and methods of ascertainment. Incidence of the studied comorbidities was rarely reported. Irritable bowel syndrome and chronic lung disease had a prevalence of more than 10% in the MS population. Irritable bowel syndrome, fibromyalgia, cataracts and glaucoma were more common than expected in the MS population. Conclusion: Although they have been the subject of less study than other comorbidities, irritable bowel syndrome, arthritis, and chronic lung disease are common in the MS population and occur more often than expected when compared to the general population