Background/objective:
In 2019, the 2010 U.S. multiple sclerosis (MS) prevalence was robustly estimated (265.1–309.2/100,000) based on large administrative health-claims datasets. Using 56.6 million ...electronic health records (EHRs), we sought to generate complementary age, sex, and race standardized estimates.
Methods/results:
Using de-identified EHRs and 2018 U.S. Census data, we estimated an age- and sex-standardized MS prevalence of 219.5/100,000 which increased to 274.5/100,000 when accounting for White and Black race alone. Women aged 50 to 69 years had the highest prevalence (>600/100,000). Among White and Black Americans, the age- and sex-standardized prevalence was 283.7 and 226.1 per 100,000, respectively.
Conclusion:
Using 56.6 million EHRs and standardizing for age, sex, and race (White and Black Americans only), we estimated at least 810,504 Americans were living with MS in 2018.
Background
Multiple sclerosis (MS) is a chronic neuroinflammatory disease with highest incidence during the period of optimal reproductive health. This scoping review aimed to identify and summarize ...available data on sexual/reproductive health in males with MS (MwMS).
Methods
This review was based on PRISMA extension for Scoping Review. PubMed database was searched for keyword “multiple sclerosis” alongside keywords “sexual health”, “reproductive health”, “family planning”, “male fertility”, “male infertility”, “sexual dysfunction”, and “erectile dysfunction”, iteratively using the “AND” logical operator. Descriptive analysis was performed on the included articles.
Results
Thirty-four studies were included, and four topics emerged: sexual dysfunction, erectile dysfunction, fertility, and family planning. Sexual dysfunction is common in MwMS (35–72%), yet only a minority of MwMS discuss their sexual health with their treatment teams. Both MS disability and depression were associated with sexual dysfunction in MwMS, with erectile dysfunction and decreased libido as the most prevalent aspects of sexual dysfunction. Positively, phosphodiesterase-5 inhibitors appear effective for treating erectile dysfunction and improving sexual quality of life in MwMS. There may also be a relationship between MS and male infertility, though changes in sexual behavior may underlie this association. Finally, a prominent knowledge gap was observed for disease-modifying therapy use and family planning in MwMS.
Conclusion
Sexual dysfunction is common, impacted by MS severity, and associates with decreased quality of life in MwMS. Communication barriers regarding sexual and reproductive health appear to exist between MwMS and providers, as do literature gaps related to MS therapeutics and sexual/reproductive health.
Loss of ambulation is common and highly variable in Parkinson's disease (PD), and poorly understood from the perspectives of those with PD. Gaining insights to the anticipated perceived trajectories ...and their drivers, will facilitate patient-centered care. Latent class growth analysis, a person-centered mixture modelling approach, was applied to 16,863 people with PD stratified by early (N = 8612; < 3 years), mid (N = 6181; 3-10 years) and later (N = 2070; > 10 years) disease to discern clusters with similar longitudinal patterns of self-reported walking difficulty, measured by EuroQoL 5D-5L that is validated for use in PD. There were four clusters in early and mid-disease strata, with a fifth identified in later disease. Trajectories ranged from none to moderate walking difficulty, with small clusters with severe problems. The percentage of subjects with moderate (early = 17.5%, mid = 26.4%, later = 32.5%) and severe (early = 3.8%, mid = 7.4%, later = 15.4%) walking difficulty at baseline increased across disease duration groups. The trajectories tended to be stable with variability in moderate and severe groups. Across strata, clusters with moderate to severe problems were associated with more severe impairment, depression, anxiety, arthritis, higher BMI, lower income, and lower education, but no consistent race or gender differences. The findings reveal distinct longitudinal patterns in perceived difficulties in walking in PD.
Background:
Neuromyelitis optic spectrum disorder (NMOSD) is a rare demyelinating, autoimmune disease and the burden in United States is not well characterized.
Objective:
The objective of this study ...was to determine the 2022 US prevalence of NMOSD.
Methods:
We constructed a cross-sectional study using aggregated electronic health record data for 25.7 million patients who had a 2022 clinical encounter. The data originated from the TriNetX US Collaborative Network of 55 healthcare organizations that span all 50 states. NMOSD prevalence was determined by querying for age-interval, sex, and race combinations, with direct standardization to the 2022 US Census data.
Results:
There were 1772 NMOSD patients among 25,743,039 patients for a prevalence of 6.88/100,000. Prevalence was the highest in Blacks (12.99/100,000) who represented 27.7% of NMOSD patients, then Asians (9.41/100,000and Whites (5.58/100,000). Among females, the prevalence of NMOSD was 9.48/100,000, and Black and Asian females had a 2.65- and 1.94-times higher prevalence than White females. In males, the prevalence of NMOSD was 3.52/100,000 and it did not differ by race. We observed a 3/5:1 female-to-male ratio in NMOSD. The age- and sex-adjusted 2022 estimate of persons with NMOSD in the United States was 15,413 females and 6233 males.
Conclusion:
We estimate that there were near 22,000 Americans living with NMOSD in 2022.
Genes associated with increased susceptibility to multiple sclerosis (MS) have been identified, but their functions are incompletely understood. One of these genes codes for the RNA helicase ...DExD/H-Box Polypeptide 39B (DDX39B), which shows genetic and functional epistasis with interleukin-7 receptor-α gene (
) in MS-risk. Based on evolutionary and functional arguments, we postulated that DDX39B enhances immune tolerance thereby decreasing MS risk. Consistent with such a role we show that DDX39B controls the expression of many MS susceptibility genes and important immune-related genes. Among these we identified
(
), which codes for the master transcriptional factor in CD4
/CD25
T regulatory cells. DDX39B knockdown led to loss of immune-regulatory and gain of immune-effector expression signatures. Splicing of
introns, which belong to a previously unrecognized type of introns with C-rich polypyrimidine tracts, was exquisitely sensitive to DDX39B levels. Given the importance of FOXP3 in autoimmunity, this work cements DDX39B as an important guardian of immune tolerance.
Background:
Age at onset of multiple sclerosis (MS) is an objective, influential predictor of the evolution of MS independent of disease duration.
Objectives:
Determine the influence of MS genetic ...predisposition on age of onset.
Methods:
We conducted a comprehensive investigation of MS risk variants and age at onset in 3495 non-Latinx white individuals, including for combinations of HLA-DRB1*15:01 alleles and quintiles of an unweighted genetic risk score (GRS) for 198 of 200 autosomal MS risk variants that reside outside the major histocompatibility complex.
Results:
The mean age at onset was 32 years, 29% were male, and 46% were HLA-DRB1*15:01 carriers. For those with the greatest genetic risk burden (the highest GRS quintile with two HLA-DRB1*15:01 alleles) were on average 5 years younger at onset (p = 0.002) than those with the lowest genetic risk burden (the lowest GRS quintile with no HLA-DRB1*15:01 alleles). There was a strong inverse relationship between the MS genetic risk burden and age at onset of MS (p < 5 × 10−8).
Conclusion:
We demonstrate a significant gradient between elevated MS genetic risk burden and an earlier onset of MS, suggesting that a higher MS genetic risk burden accelerates onset of the disease.
Most genotype–phenotype studies have historically lacked population diversity, impacting the generalizability of findings and thereby limiting the ability to equitably implement precision medicine. ...This well-documented problem has generated much interest in the ascertainment of new cohorts with an emphasis on multiple dimensions of diversity, including race/ethnicity, gender, age, socioeconomic status, disability, and geography. The most well known of these new cohort efforts is arguably All of Us, formerly known as the Precision Medicine Cohort Initiative Program. All of Us intends to ascertain at least one million participants in the United States representative of the multiple dimensions of diversity. As an incentive to participate, All of Us is offering the return of research results, including whole genome sequencing data, as well as the opportunity to contribute to the scientific process as non-scientists. The scale and scope of the proposed return of research results are unprecedented. Here, we briefly review possible return of genetic data models, including the likely data file formats and modes of data transfer or access. We also review the resources required to access and interpret the genetic or genomic data once received by the average participant, highlighting the nuanced anticipated barriers that will challenge both the digitally, computationally literate and illiterate participant alike. This inventory of resources required to receive, process, and interpret return of research results exposes the potential for access disparities and warns the scientific community to mind the gap so that all participants have equal access and understanding of the benefits of human genetic research.
Neurocognitive testing is a critical tool in the management of sport-related concussions. Adversity during childhood and adolescence affects cognitive tasks, behavioral outcomes, and academic ...performance. Adversity may be important in baseline concussion test validity as well; however, the influence of these experiences is not well understood.
To examine the relationship between individual-level experiences of adversity and baseline test validity of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). We hypothesized that experiences of poverty, maltreatment, or extreme neighborhood deprivation would be associated with lower odds of baseline test validity.
Case-control study.
Cuyahoga County, Ohio.
A total of 6495 student-athletes born from 1995 through 2005 who completed a baseline ImPACT test between 10 and 18 years old and were identified in the Child-Household Integrated Longitudinal Data system, a comprehensive data system with demographic and social service usage outcomes for children in Cuyahoga County, Ohio.
Baseline concussion test validity was determined using the ImPACT built-in validity measure. Experiences of adversity during the sensitive developmental periods of early childhood and adolescence were key independent variables.
Our findings suggested that social mobility may play an important role in baseline validity. Youth with upward social mobility (ie, poverty or neighborhood deprivation in early childhood only) were not different from youth without such experiences (odds ratio OR = 0.91, P = .74). Youth with persistent adversity across childhood or downward social mobility (ie, poverty or high neighborhood deprivation in adolescence only) had 50% to 72% lower odds of achieving a valid baseline test (persistent poverty, OR = 0.59, P = .05; adolescent poverty only, OR = 0.50, P = .004; adolescent neighborhood deprivation only, OR = 0.28, P < .001). Maltreatment had no significant effect on test validity.
These findings indicated that certain patterns of adversity may predispose youth to invalid baseline testing scores, potentially increasing their risk of inappropriate injury management and poor outcomes.
Background/Objective:
Hypertension (HTN) is common in multiple sclerosis (MS), and it is associated with poorer outcomes. We sought to characterize HTN age at onset (AAO) by MS status.
...Methods/Results:
There were 130,050 incident HTN patients, among whom there were 892 MS patients. We conducted multivariable linear regression adjusting for patient attributes. Sex- and race-stratified models were conducted. HTN AAO did not differ in patients with and without MS (p = 0.17). Similar null associations were observed in the sex- and race-specific analyses.
Conclusion:
While there are complex relationships between HTN and MS, there are no differences in HTN AAO by MS status.
Background
Predicting the transition from relapsing–remitting (RR) to secondary-progressive (SP) multiple sclerosis (MS) from early in the disease course is challenging.
Objective
To construct ...prediction models for SPMS using sociodemographic and self-reported clinical measures that would be available at/near MS onset, with specific considerations for MS genetic risk factors.
Methods
We conducted a retrospective cross-sectional study based on 1295 white, non-Hispanic individuals. Cox proportional hazard prediction models were generated for three censored SPMS outcomes (ever transitioning, transitioning within 10 years, and transitioning within 20 years) using sociodemographic, comorbid health information, symptomatology, and other measures of early disease activity.
HLADRB1*15:01
and
HLA-A*02:01
, as well as a genetic risk score, were iteratively considered in each model. We also explored the relationships for all 200 MS risk variants located outside the major histocompatibility complex. Nomograms were generated for the final prediction models.
Results
An older age of MS onset and being male predicted a short latency to SPMS, while a longer interval between the first two relapses predicted a much longer latency. Comorbid conditions and onset symptomatology variably predicted the risk for transitioning to SPMS for each censored outcome. The most notable observation was that
HLA-A*02:01
, which confers decreased risk for MS, also contributed to decreased hazards for SPMS.
Conclusions
These results have the potential to advance prognostication for a person with MS using information available at or near onset, potentially improving care and quality of life for those who live with MS.
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