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  • 1
    Online Resource
    Online Resource
    Evaluating Vitamin D Repletion Regimens and Effects in Veteran Patients
    SAGE Publications ; 2015
    In:  Annals of Pharmacotherapy Vol. 49, No. 9 ( 2015-09), p. 969-977
    Details
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 49, No. 9 ( 2015-09), p. 969-977
    Abstract: Background: There are wide variations in recommended dosing for vitamin D repletion. The identification of specific dosing thresholds to optimize repletion of 25-hydroxyvitamin D3 (also known as 25(OH)D) may help narrow the wide spectrum of vitamin D dosing. Objective: The primary objective of this study was to evaluate vitamin D treatment regimens and their dose response effect on vitamin D serum levels. Secondary outcomes include evaluation of the frequency of monitoring vitamin D serum levels and prescription adherence. Methods: This was a multicenter, retrospective data extraction analysis conducted in patients who initiated monotherapy of ergocalciferol and cholecalciferol between January 1, 2005 and December 31, 2010. Following vitamin D therapy initiation, changes in laboratory values, frequency of laboratory monitoring, and prescription adherence were assessed. Ergocalciferol and cholecalciferol groups were separately organized into quartiles to identify dosing ranges that had the most impact on changes in 25(OH)D laboratory values. Results: There were 2272 and 4140 monotherapy patients in the ergocalciferol and cholecalciferol groups, respectively. Cholecalciferol mean doses between 600 and 1100 IU had similar changes in 25(OH)D ranging from 8 to 9.1 ng/mL. Cholecalciferol mean doses of 2700 IU had 12.7 ng/mL 25(OH)D increase ( P 〈 0.05). Ergocalciferol at mean doses of 11 000 IU had a 19.9 ng/mL increase of 25(OH)D ( P 〈 0.05). At baseline 25(OH)D levels less than 15 ng/mL, 90% of subjects reached a therapeutic 25(OH)D level with a cumulative 300 000 IU cholecalciferol dose. Adherence, calculated by medication possession ratio, was greater with cholecalciferol than ergocalciferol (87% compared with 68%). Conclusions: Lower vitamin D dose ranges had a comparable effect on 25(OH)D change. Higher doses can produce higher levels, but the relationship is not linear.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1177/1060028015591034
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2053518-1
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  • 2
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    Genetic risk factors for pediatric-onset multiple sclerosis
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 14 ( 2018-12), p. 1825-1834
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 14 ( 2018-12), p. 1825-1834
    Abstract: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset 〈 18 years ( n = 569) and controls ( n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases ( n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR) meta  = 2.95, p  〈  2.0 × 10 −16 ). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p  〈  0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (OR avg  = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (OR meta  = 2.77, 95% confidence interval: 2.33, 3.32, p  〈  2.0 × 10 −16 ) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517733551
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2008225-3
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  • 3
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    Dietary factors and pediatric multiple sclerosis: A case-control study
    SAGE Publications ; 2018
    In:  Multiple Sclerosis Journal Vol. 24, No. 8 ( 2018-07), p. 1067-1076
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 24, No. 8 ( 2018-07), p. 1067-1076
    Abstract: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, 〈 4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging). The validated Block Kids Food Screener questionnaire was administered 2011–2016. Chi-squared test compared categorical variables, Kruskal–Wallis test compared continuous variables, and multivariable logistic regression analysis was performed. Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases ( p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p  〈  0.001). In multivariable analysis, iron consumption below recommended guidelines was associated with MS (odds ratio = 1.80, p  〈  0.01). Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458517713343
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2008225-3
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  • 4
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    Vitamin D genes influence MS relapses in children
    SAGE Publications ; 2020
    In:  Multiple Sclerosis Journal Vol. 26, No. 8 ( 2020-07), p. 894-901
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 26, No. 8 ( 2020-07), p. 894-901
    Abstract: The aim of this study was to determine whether a vitamin D genetic risk score (vitDGRS) is associated with 25-hydroxyvitamin D (25(OH)D) level and multiple sclerosis (MS) relapses in children. Methods: DNA samples were typed for single nucleotide polymorphisms (SNPs) from four genes previously identified to be associated with 25(OH)D levels. SNPs with strong associations with 25(OH)D after multiple comparison correction were used to create a genetic risk score (vitDGRS). Cox regression models tested associations of vitDGRS with relapse hazard. Results: Two independent SNPs within or near GC and NADSYN1/DHCR7 genes were strongly associated with 25(OH)D levels in the discovery cohort ( n = 182) after Bonferroni correction. The vitDGRS of these SNPs explained 4.5% of the variance of 25(OH)D level after adjustment for genetic ancestry. Having the highest versus lowest vitDGRS was associated with 11 ng/mL lower 25(OH)D level (95% confidence interval (CI) = −17.5, −4.5, p = 0.001) in the discovery cohort. Adjusting for ancestry, sex, disease-modifying therapy (DMT), and HLA-DRB1*15 carrier status, the highest versus lowest vitDGRS was associated with 2.6-fold (95% CI = 1.37, 5.03, p = 0.004) and 2.0-fold (95% CI = 0.75, 5.20, p = 0.16) higher relapse hazard in the discovery and replication cohorts, respectively. Conclusion: The vitDGRS identifies children at greater risk of relapse. These findings support a causal role for vitamin D in MS course.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458519845842
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2008225-3
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  • 5
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    Acquisition of Early Developmental Milestones and Need for Special Education Services in Pediatric Multiple Sclerosis
    SAGE Publications ; 2019
    In:  Journal of Child Neurology Vol. 34, No. 3 ( 2019-03), p. 148-152
    Details
    In: Journal of Child Neurology, SAGE Publications, Vol. 34, No. 3 ( 2019-03), p. 148-152
    Abstract: Children with pediatric-onset multiple sclerosis and pediatric controls were enrolled across 16 pediatric multiple sclerosis centers in the United States and completed questionnaires that addressed time of first unaided walking and acquisition of 2-word phrases. A total of 467 (308 female) cases and 428 (209 female) controls were enrolled. Pediatric multiple sclerosis (n = 467) were not delayed in walking or using 2-word phrases compared to healthy controls (n = 428) (2.2% vs 5.7%, respectively). Children with disease onset before age 11 versus onset at 11 years or after were more likely to need an individualized education plan ( P = .002), reading assistance ( P = .0003), and math assistance ( P = .001). Children with multiple sclerosis onset prior to age 18 are not delayed in meeting the 2 major early developmental milestones but do have a significantly increased use of special services or learning assistance at school. Further research will need to address whether other measures of development (eg, rate of language acquisition or fine motor skills) differ between pediatric multiple sclerosis and controls.
    Type of Medium: Online Resource
    ISSN: 0883-0738 , 1708-8283
    URL: Article
    DOI: 10.1177/0883073818815041
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2068710-2
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  • 6
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    Help-Seeking Experiences of Youth with Suicidal Ideations
    SAGE Publications ; 2014
    In:  Journal of Patient Experience Vol. 1, No. 2 ( 2014-11), p. 22-27
    Details
    In: Journal of Patient Experience, SAGE Publications, Vol. 1, No. 2 ( 2014-11), p. 22-27
    Abstract: Approximately 28 percent of Canadians begin to experience a mental health issue during their youth. In this article, we explore patients' perceptions of their mental healthcare experiences within a sample of youth who reported anxiety or depressive symptoms and past suicidal ideations. The study data is taken from in-depth interviews with 23 youth in British Columbia. Interview topics included support systems, help-seeking behavior and healthcare experiences. Our findings indicate that participant experiences were most positive when experiences were neither dismissive nor stigmatizing. Important factors for participants were respect, acknowledgement, information and choice. Our results generated the concept that treatment perceptions for youth with suicidal behaviours can be placed on a theoretical spectrum, which may be a useful tool for self reflection for those who support individuals with mental health conditions professionally or personally.
    Type of Medium: Online Resource
    ISSN: 2374-3735 , 2374-3743
    URL: Article
    DOI: 10.1177/237437431400100205
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2857285-3
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  • 7
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    Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline
    SAGE Publications ; 2020
    In:  Multiple Sclerosis Journal Vol. 26, No. 14 ( 2020-12), p. 1938-1947
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 26, No. 14 ( 2020-12), p. 1938-1947
    Abstract: Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS. Objective: To screen for cognitive impairment early in the course of POMS and analyze predictive factors. Methods: Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free. Results: At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing ( n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT. Conclusion: Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/1352458519891984
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2008225-3
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  • 8
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    Rare and low-frequency coding genetic variants contribute to pediatric-onset multiple sclerosis
    SAGE Publications ; 2023
    In:  Multiple Sclerosis Journal Vol. 29, No. 4-5 ( 2023-04), p. 505-511
    Details
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 29, No. 4-5 ( 2023-04), p. 505-511
    Abstract: Rare genetic variants are emerging as important contributors to the heritability of multiple sclerosis (MS). Whether rare variants also contribute to pediatric-onset multiple sclerosis (POMS) is unknown. Objective: To test whether genes harboring rare variants associated with adult-onset MS risk ( PRF1, PRKRA, NLRP8, and HDAC7) and 52 major histocompatibility complex (MHC) genes are associated with POMS. Methods: We analyzed DNA samples from 330 POMS cases and 306 controls from the US Network of Pediatric MS Centers and Kaiser Permanente Northern California for which Illumina ExomeChip genotypes were available. Using the gene-based method “SKAT-O,” we tested the association between candidate genes and POMS risk. Results: After correction for multiple comparisons, one adult-onset MS gene ( PRF1, p = 2.70 × 10 −3 ) and two MHC genes ( BRD2, p = 5.89 × 10 −5 and AGER, p = 7.96 × 10 −5 ) were significantly associated with POMS. Results suggest these are independent of HLA-DRB1*1501. Conclusion: Findings support a role for rare coding variants in POMS susceptibility. In particular, rare minor alleles within PRF1 were more common among individuals with POMS compared to controls while the opposite was true for rare variants within significant MHC genes, BRD2 and AGER. These genes would not have been identified by common variant studies, emphasizing the merits of investigating rare genetic variation in complex diseases.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    URL: Article
    DOI: 10.1177/13524585221150736
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2008225-3
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