Is infertility more common among patients with multiple sclerosis? Implications for utilization of assisted reproductive techniques.

RESEARCH QUESTION: Is fertility affected in women with multiple sclerosis (MS), and what is their usage of assisted reproductive technology (ART)? DESIGN: Data regarding multiple sclerosis and ART usage among patients with multiple sclerosis were extracted from the Israeli health maintenance organization Clalit Health Service database. Data regarding the diagnosis and treatment of multiple sclerosis, cause of infertility and use of fertility treatments were collected for all female multiple sclerosis patients aged 18-45 years between 2005 and 2021. Each patient was matched by age in a 1:10 ratio with reference women from the general population. The prevalence of infertility was compared between the two groups. Univariate and multivariate statistical tests were used to analyse the association between multiple sclerosis and fertility treatments including IVF and ovarian stimulation. RESULTS: During the study period, 1309 multiple sclerosis patients were compared with 13,090 controls from the general population matched for age. The mean age was 29 ± 7.8 years. The overall prevalence of infertility was 15.4% (202/1309) among the multiple sclerosis patients, similar to the general population (16.3%; 2129/13090) (P = 0.436). The prevalence of IVF and ovarian stimulation was similar among multiple sclerosis patients and matched controls from the general population (8.1% versus 7.2%, P = 0.240; 13.8% versus 14.3%; P = 0.624, respectively). CONCLUSIONS: The results show similar rates of infertility and fertility treatments among multiple sclerosis patients and the general population. This provides reassurance that fertility among women with multiple sclerosis does not differ from that of women in the general population, and indicates there is no excessive usage of ART.

Multiple Sclerosis-Associated Gut Microbiome in the Israeli Diverse Populations: Associations with Ethnicity, Gender, Disability Status, Vitamin D Levels, and Mediterranean Diet.

Microbiome dysbiosis is increasingly being recognized as implicated in immune-mediated disorders including multiple sclerosis (MS). The microbiome is modulated by genetic and environmental factors including lifestyle, diet, and drug intake. This study aimed to characterize the MS-associated gut microbiome in the Israeli populations and to identify associations with demographic, dietary, and clinical features. The microbiota from 57 treatment-naive patients with MS (PwMS) and 43 age- and gender-matched healthy controls (HCs) was sequenced and abundance compared. Associations between differential microbes with demographic or clinical characteristics, as well as diet and nutrient intake, were assessed. While there was no difference in α- or ß-diversity of the microbiome, we identified 40 microbes from different taxonomic levels that differ in abundance between PwMS and HCs, including Barnesiella, Collinsella, Egerthella, Mitsuokella, Olsenella Romboutsia, and Succinivibrio, all enhanced in PwMS, while several members of Lacnospira were reduced. Additional MS-differential microbes specific to ethnicity were identified. Several MS-specific microbial patterns were associated with gender, vitamin D level, Mediterranean diet, nutrient intake, or disability status. Thus, PwMS have altered microbiota composition, with distinctive patterns related to geographic locations and population. Microbiome dysbiosis seem to be implicated in disease progression, gender-related differences, and vitamin D-mediated immunological effects recognized in MS. Dietary interventions may be beneficial in restoring a "healthy microbiota" as part of applying comprehensive personalized therapeutic strategies for PwMS.

Beliefs about medication as predictors of medication adherence in a prospective cohort study among persons with multiple sclerosis.

BACKGROUND: Though adherence to disease-modifying therapies (DMTs) among persons with multiple sclerosis (PwMS) varies and is often below 80%, only few prospective studies on adherence examined predictors beyond demographic and clinical characteristics. OBJECTIVES: Identify antecedents to adherence and persistence to DMT in a prospective design among PwMS. METHODS: PwMS (n = 186) were prospectively assessed at three time points: baseline, 6 (Time 1) and 12 months later (Time 2). Clinical, demographic information and patient-reported medication beliefs, illness perceptions, medication habits, perceived health and affect were surveyed in-person. Adherence and persistence were assessed by a combination of self-reports and retrospective review of medication claims. FINDINGS: PwMS were 69.9% (Time 1) and 71% (Time 2) adherent to their DMTs and 64.5.9% were persistent. Beliefs about Medications were consistently predictive at both time points (baseline to Time 1 and Time 1 to Time 2) of medication adherence and persistence whereas other perceptions were predictive in some analyses; clinical and demographic characteristics were mostly not predictive of adherence nor persistence. The prospective association of beliefs about medication with adherence held also in multivariate analyses (OR = 0.88, 95% CI 0.78-0.99, p = 0.029). CONCLUSIONS: Adherence and persistence are predicted by medication beliefs of PwMS. As medication beliefs are modifiable, they should be assessed periodically and targeted as a focus of tailored interventions aimed to improve adherence and consequently health outcomes in PwMS. REGISTRATION: Clinical trials registry # NCT02488343 , date: 06/08/2015.

Caring for patients with venomous Crotalinae snakebites.

Venomous snakebites are surprisingly common in the US. This article provides an overview of what to do when a patient has been bitten by a North American pit viper, a venomous subset of indigenous snakes.

Effector and regulatory B cells in Multiple Sclerosis.

The role of B cells in the pathogenesis of Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, is becoming eminent in recent years, but the specific contribution of the distinct B cell subsets remains to be elucidated. Several B cell subsets have shown regulatory, anti-inflammatory capacities in response to stimuli in vitro, as well as in the animal model of MS: Experimental Autoimmune Encephalomyelitis (EAE). However, the functional role of the B regulatory cells (Bregs) in vivo and specifically in the human disease is yet to be clarified. In the present review, we have summarized the updated information on the roles of effector and regulatory B cells in MS and the immune-modulatory effects of MS therapeutic agents on their phenotype and function.

Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.

OBJECTIVE: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. METHODS: The transcriptome and methylome of peripheral monocytes were compared between monozygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples. RESULTS: >100 differentially expressed genes and ∼1800 differentially methylated CpGs were detected in peripheral monocytes between MG patients and controls. Several transcripts associated with immune homeostasis and inflammation resolution were reduced in MG patients. Only a relatively few genes differed between the discordant healthy and MG co-twins, and both their expression and methylation profiles demonstrated very high similarity. INTERPRETATION: This is the first study to characterize the DNA methylation profile in MG, and the expression profile of immune cells in MZ twins with MG. Results suggest that numerous small changes in gene expression or methylation might together contribute to disease. Impaired monocyte function in MG and decreased expression of genes associated with inflammation resolution could contribute to the chronicity of the disease. Findings may serve as potential new predictive biomarkers for disease and disease activity, as well as potential future targets for therapy development. The high similarity between the healthy and the MG discordant twins, suggests that a molecular signature might precede a clinical phenotype, and that genetic predisposition may have a stronger contribution to disease than previously assumed.

Shifting paradigms in multiple sclerosis: from disease-specific, through population-specific toward patient-specific.

PURPOSE OF REVIEW: In recent years we notice paradigm shifts in the understanding of multiple sclerosis (MS), leading to important transition in the patients' management. This review discusses some of the recent findings and developments underlying the conceptual changes being translated from 'treating the disease' to 'treating the patient' with MS (PwMS). RECENT FINDINGS: Applying advanced technologies combined with cross-disciplinary efforts in the fields of neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology provided support for the notion that MS is not a single disease but rather a spectrum. Predictive markers of disease subtypes, disease activity and response to therapy are being developed; some already applied to practice, allowing informed management. In parallel, population-specific issues, some genetic-driven, others caused by environmental (sun-exposure, life-style, etc.), gender-related (hormones) and epigenetic factors, are being elucidated. Additionally, patient empowerment-based approaches, including integration of patient-reported outcome measures (PRO) as well as tools to enhance patients' adherence to medications, are being developed, some already provided as part of emerging mobile-health technologies. SUMMARY: Developments in the MS field, elucidating disease subtypes and interpopulation diversities, together with integration of patient-centered approaches, allow transition toward precision medicine in MS clinical trials and patient care.

Fingolimod therapy modulates circulating B cell composition, increases B regulatory subsets and production of IL-10 and TGFß in patients with Multiple Sclerosis.

Fingolimod, an oral therapeutic agent approved for patients with relapsing-remitting Multiple Sclerosis (MS), has been shown to prevent lymphocyte egress from secondary lymphoid tissues; however the specific drug effect on B cells in fingolimod-treated patients remains to be fully elucidated. We present here a comprehensive analysis on the proportions of B cell subsets in the periphery, and the levels of activation, functional surface markers and cytokine profile of B cells in MS patients, following initiation of fingolimod therapy, using flow cytometry and cytokine bead array. Fingolimod therapy increased the ratio of naïve to memory cells, elevated the percentage of plasma cells and highly increased the proportion of transitional B cells as well as additional regulatory subsets, including: IL10(+), CD25(+) and CD5(+) B cells. The percentage of activated CD69(+) cells was highly elevated in the remaining circulating B cells, which produced increased levels of IL10, TGFß, IL6, IL4, LTα, TNFα and IFNγ cytokines, with an overall increased ratio of TGFß to pro-inflammatory cytokines. Furthermore, fingolimod therapy reduced ICAM-1(+) cells, suggesting a possible reduction in antigen-presenting capacity. Phosphorylated-fingolimod was shown in vitro to reduce S1PR1 RNA and protein, to slightly increase viability and to activate anti-apoptotic Bcl2 in transformed B cells of patients with MS. In conclusion, fingolimod therapy modulates significantly the composition of circulating B cells, promoting regulatory subsets and an anti-inflammatory cytokine repertoire.

Genetic basis of myasthenia gravis - a comprehensive review.

Myasthenia gravis (MG) is a rare autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane in the neuromuscular junction. The estimated number of MG patients is steadily increasing, and it had more than doubled in the last 20 years. Monozygotic MG twin concordance is estimated to be about 35% supporting the central role of environmental factors in MG etiology. Epigenetics, presume to be the mechanistic link between environmental and genetic risk factors in disease development, provides support for specific microRNAs associated with MG. Genetic studies have mainly pointed at specific HLA alleles implicated in MG susceptibility, however recently both TNFAIP3-interacting protein 1 (TNIP1) and tyrosine phosphatase non-receptor 22 (PTPN22) were indicated to be associated with MG in a GWAS study. A gender bias was observed for SNPs in the HLA-locus, suggesting female-specific alleles have an increase risk for MG. Moreover, sex hormones play a pivotal role in the gender bias in autoimmunity in general and in MG in particular. Hence the genetic basis of gender bias might be highly pertinent to MG and deserves further characterization. Pathway-based analyses that combine information across multiple genes into a limited number of molecular networks have been found to be a powerful approach. Both regulatory T-cell (Treg) differentiation and NF-κB signaling pathway have been shown to have relevance to MG pathophysiology. Hence studies centered around two pathways might be a fruitful approach to identify additional polymorphisms associated with myasthenia gravis.

Personalized Intervention to Improve Medication Adherence for Persons with Multiple Sclerosis.

Purpose: To evaluate the acceptability, retention, and efficacy of face-to-face intervention, incorporating education and Motivational Interviewing (MI) to support persons with relapsing-remitting multiple sclerosis (PwRRMS) and increase self-reported medication adherence. Patients and Methods: PwRRMS (N = 60) prescribed Disease Modifying Treatment (DMT), who were identified as non-adherent and consented to participate in an intervention, received verbal education and counseling from their treating physician, a tailored MI counseling and a booster session via telephone with a health psychologist, and a concluding MI counseling six months later. Each PwRRMS filled a battery of patient-reported outcomes (PROs) at baseline, six and 12 months later. The design was a quasi-experimental pre-test post-test across a year. Results: Of the sixty identified persons who consented to enroll, 52 completed the intervention and 46 completed the follow-up. At six months following the baseline, adherence scores increased (median = 12.0) and were significantly different than at baseline (median=10.0, p = 0.030). Still, at 12 months follow-up there was no significant difference from baseline in reported adherence (median = 11.0, p = 0.106). Conclusion: This study demonstrated reasonable retention and initial efficacy of a combined psycho-education and MI protocol for PwRRMS to enhance medication adherence to DMT. To maintain the change, a more sustained intervention is required.

The study focused on persons with relapsing-remitting multiple sclerosis (PwRRMS) who do not adhere to their prescribed medication. Following the identification of non-adherent persons, PwRRMS were offered an intervention to increase their adherence. The study examined how many of those identified consented to enroll in the intervention, how many remained in the intervention, and whether the intervention was efficacious in terms of self-reported adherence. The intervention included verbal education and counseling from the treating physician, immediately followed by tailored counseling by a psychologist. There was a booster session via telephone with the psychologist, and a concluding counseling meeting six months later. Participants were followed for a year after the initial counseling. Two-thirds of PWMS identified as non-adherent consented to enroll (n = 60), 52 completed the intervention and 46 completed the follow-up. At six months following counseling, self-reported adherence scores significantly increased, but at 12 months follow-up there was no significant difference from baseline in reported adherence. To maintain the change, a more sustained intervention is required.

Familial vs sporadic multiple sclerosis in the Israeli population: Differences in ethnicity distribution and disease progression, with anticipation in successive generations.

BACKGROUND: Multiple Sclerosis (MS) may cluster in families, an entity known as familial MS (FMS), possibly due to aggregation of genetic and environmental factors. Though previous studies have characterized FMS in different populations, no study to the best of our knowledge has yet characterized FMS in the unique Israeli population, which is comprised of relatively endogamous ethnicities. Our goal in this study was to compare demographic and clinical characteristics between FMS and sporadic MS (SMS), and to search for intra-familial patterns. METHODS: In a retrospective study of 101 FMS patients and 508 SMS patients, ethnicity and sex distribution was assessed. Clinical aspects were compared between 172 paired FMS and SMS patients, matched for sex, age and ethnicity, and between generations of the FMS cohort. RESULTS: Females comprised 75.3 % of FMS and 67.5 % of SMS patients (p = 0.1). Ethnic distribution was significantly different between FMS and SMS (p = 0.014), with the former comprising a higher proportion of Christian-Arabs (15.4% vs. 5.1 %, p = 0.004) and lower proportion of Jews (60% vs. 74.2 %, p = 0.016). Age at disease onset or diagnosis, frequency of positive Oligoclonal bands and comorbidity of other autoimmune/inflammatory disease or chronic diseases was comparable between FMS and SMS, yet motor symptoms at onset were more prevalent in FMS (34% vs. 20 %, p = 0.02). Annualized relapse rates throughout 10 years from onset were comparable. Among FMS, mean Expanded-Disability-Status-Scale (EDSS) and slope of deterioration in EDSS over 20 years from diagnosis were higher (p = 0.0004 and p = 0.023, respectively), time to EDSS ≥ 3 was shorter (7.1 vs. 12.1 years, HR 1.6, p = 0.036) and MS-Severity-Score (MSSS) was higher (3.84 vs. 2.95, p = 0.04), compared to SMS. Following adjustment for smoking, which tended to be higher among FMS patients (P = 0.06), mean EDSS and slope of deterioration in EDSS over 20 years remained significantly higher (p = 0.0006 and p = 0.025, respectively) in FMS, time to EDSS ≥ 3 tended to be higher (HR 1.5, p = 0.06), while MSSS was comparable. An inter-generational analysis of the total FMS cohort, as well as an intra-familial analysis, both adjusted for year of diagnosis, revealed significantly earlier age of onset (p < 0.0001 and p < 0.0001) and diagnosis (p = 0.001 and p < 0.0001) in the younger compared to the older generations, respectively. CONCLUSION: In this Israeli cohort, the proportions of specific ethnicities differ between FMS and SMS, indicating that FMS has a population-specific prevalence pattern, and that further investigation for susceptibility genes is warranted. Disease progression is faster in FMS patients and anticipation is observed in families with multiple cases of MS. Closer surveillance and application of a pro-active induction or early highly-effective therapeutic strategy for FMS patients should be considered, to reduce high disease activity and fast disability progression.

The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) incidence is higher in geographic regions with less sunlight exposure. Both vitamin D and melatonin are essential mediators of the effect of sunlight in health, and as such are candidates to play a key role in MS. We hypothesized that vitamin D and melatonin may have related influences in patients with MS. METHODS: In a randomized, double blind study of 40 IFN-ß treated MS patients, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. Serum 25-hydroxy-vitamin-D (25-OH-D) and nighttime urine melatonin metabolite, 6-sulphatoxy-melatonin (6-SMT), were measured at baseline, 3 months and 1 year from enrolment. RESULTS: After 3 months supplementation, 25-OH-D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group. After 1 year, a decrease in 25-OH-D levels, accompanied by an increase of urine nighttime 6-SMT were observed in the high dose group. Percent change in serum 25-OH-D was significantly and negatively correlated with percent change in urine 6-SMT after 3 months and between 3 months to 1 year. 25-OH-D levels by the end of the study were significantly and negatively correlated to BMI. CONCLUSIONS: Melatonin secretion is negatively correlated with alterations in serum 25-OH-D in IFN-ß treated patients with MS. The finding suggests that melatonin should be considered as a potential mediator of vitamin D neuro-immunomodulatory effects in patients with MS.

Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties.

BACKGROUND: Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-ß) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines' levels. METHODS: In a randomized, double blind study of 45 IFNß-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented. RESULTS: 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed. CONCLUSION: Vitamin D supplementation to IFN-ß treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN-ß related FLS. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01005095.

Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells.

A major goal of immunotherapy for autoimmune diseases and transplantation is induction of regulatory T cells that mediate immunologic tolerance. The mucosal immune system is unique, as tolerance is preferentially induced after exposure to antigen, and induction of regulatory T cells is a primary mechanism of oral tolerance. Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We found that orally administered CD3-specific antibody is biologically active in the gut and suppresses autoimmune encephalomyelitis both before induction of disease and at the height of disease. Orally administered CD3-specific antibody induces CD4+ CD25- LAP+ regulatory T cells that contain latency-associated peptide (LAP) on their surface and that function in vitro and in vivo through a TGF-beta-dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.

Using an Intervention Mapping Approach to Improve Adherence to Disease-Modifying Treatment in Multiple Sclerosis.

BACKGROUND: Up to 50% of individuals with multiple sclerosis (MS) who are prescribed disease-modifying treatments (DMTs) do not take them as advised. Although many studies report on DMT adherence rate, few studies report on interventions involving individuals with MS. The current paper describes the development of an intervention aimed at improving adherence to DMTs among identified nonadherent individuals with MS. METHODS: An intervention was developed using an Intervention Mapping approach, recommendations from reviews on medication adherence, and input from individuals with MS. Its content was determined by theories of health behavior (specifically, a perceptions and practicalities approach), empirical evidence collected among the specific target population (an observational "needs assessment" stage [n = 186]), and other studies. RESULTS: A personalized intervention was tailored to the reasons for nonadherence, uncovered during the observational needs assessment stage, to be delivered sequentially by a neurologist and a psychologist. After the intervention objectives were identified, components of the intervention were set: psychoeducation and ways of coping with adverse effects; modification of unhelpful treatment beliefs (such modifications were found predictive of adherence in the observational phase of the study); improving confidence and self-efficacy; and developing strategies for remembering to take DMTs. These components were embedded within motivational interviewing. CONCLUSIONS: Intervention Mapping was useful in developing an intervention grounded both in the theoretical approach of perceptions and practicalities and in empirical evidence from the literature and the target sample; concurrently, identifying determinants that the intervention did not address. The effectiveness of the intervention-which could potentially improve adherence among individuals with MS-needs to be examined.

Tight junction proteins expression and modulation in immune cells and multiple sclerosis.

The tight junction proteins (TJPs) are major determinants of endothelial cells comprising physiological vascular barriers such as the blood-brain barrier, but little is known about their expression and role in immune cells. In this study we assessed TJP expression in human leukocyte subsets, their induction by immune activation and modulation associated with autoimmune disease states and therapies. A consistent expression of TJP complexes was detected in peripheral blood leukocytes (PBLs), predominantly in B and T lymphocytes and monocytes, whereas the in vitro application of various immune cell activators led to an increase of claudin 1 levels, yet not of claudin 5. Claudins 1 and 5 levels were elevated in PBLs of multiple sclerosis (MS) patients in relapse, relative to patients in remission, healthy controls and patients with other neurological disorders. Interestingly, claudin 1 protein levels were elevated also in PBLs of patients with type 1 diabetes (T1D). Following glucocorticoid treatment of MS patients in relapse, RNA levels of JAM3 and CLDN5 and claudin 5 protein levels in PBLs decreased. Furthermore, a correlation between CLDN5 pre-treatment levels and clinical response phenotype to interferon-ß therapy was detected. Our findings indicate that higher levels of leukocyte claudins are associated with immune activation and specifically, increased levels of claudin 5 are associated with MS disease activity. This study highlights a potential role of leukocyte TJPs in physiological states, and autoimmunity and suggests they should be further evaluated as biomarkers for aberrant immune activity and response to therapy in immune-mediated diseases such as MS.

The ubiquitin-proteasome pathway regulates claudin 5 degradation.

The tight junctions (TJs) form continuous intracellular contacts, which help create selective barriers in epithelial and endothelial cell layers. The structures created by the TJs are very dynamic and can be rapidly remodeled in response to physiological and pathological signals. Claudin 5 is a membranal TJ protein which plays a critical role in determining the permeability of endothelial barriers. We describe the regulation of claudin 5 degradation by the ubiquitin-proteasome system (UPS). Our results indicate that claudin 5 has a relatively short half-life and can be polyubiquitinated on lysine 199. This ubiquitination appears to trigger the proteasome-dependent degradation of claudin 5. Other mechanisms also seem to be involved in the post-translational regulation of claudin 5, including a ubiquitin-independent and probably indirect lysosomal-dependent pathway. These findings provide evidence for the involvement of the UPS in the regulation of claudin 5 levels, and set the stage for further research to determine the involvement of this pathway in the modulation of the properties of TJs and cell-layer barriers.

Telemedicine for multiple sclerosis patients: assessment using Health Value Compass.

BACKGROUND: Telemedicine carries the potential of improving accessibility to health services, especially for disabled people. OBJECTIVE: To assess the health-related outcomes of short-term implementation of telemedicine (telemed) for MS patients. METHODS: A prospective study of 40 MS patients divided into a control group and a telemed group was conducted, in two stages: A. Six months' follow-up for measurement of baseline health-related variables; B. Implementation stage, adding home telecare to the telemed group. A Health Value Compass was applied to assess the outcomes of home telecare implementation. Clinical status, cost data, patients' self-assessment of Health Related Quality of Life (HRQoL) and satisfaction with telecare were studied. RESULTS: Patients in the telemed group demonstrated improved clinical outcome measured by symptoms severity. There was a decrease of at least 35% in the medical costs for 67% of the telemed group patients. Satisfaction with telecare was high and most patients would recommend this service to others. CONCLUSIONS: The present pilot study, applying Health Value Compass-based analysis, suggests that telecare is a powerful tool for monitoring MS patients at home, carries the potential to improve health care while reducing costs, and should be considered for implementation as part of the management of chronic neurological diseases.

Multiple sclerosis in diverse populations: characteristics in distinct Arab ethnicities in Israel.

BACKGROUND: Multiple sclerosis (MS) prevalence and genetic susceptibility varies among the different ethnic groups of Jews and Arabs in Israel. OBJECTIVE: Characterization of MS disease course in Christian, Muslim and Druze Arabs in Israel. METHODS: Historical cohort and three-year follow-up cohort analyses based on interviews and clinical charts of 149 Arab MS patients (78 Muslims, 49 Christians and 22 Druze) from three MS centers in Israel. Significant findings were adjusted for use of disease modifying therapy. RESULTS: Age of onset (means between 30 and 31 years) and incomplete recovery rates after the first relapse (~50%) were similar for Christian, Muslim and Druze patients. Low rates of primary progressive MS (≤1%) were observed. Differences between the ethnicities in the time from onset to the second neurological episode were observed among females, but not males. Druze and Muslim women were more likely to have a second event within two years from the first event compared with Christians (odds ratios =8.8, p= 0.02; odds ratio=6.6, p=0.007 respectively). Trends for higher annual relapse rates, annual disability progression rates and MS Severity Scores were observed among the Druze. CONCLUSIONS: Among the Israeli Arab female MS patients, Druze and Muslims exhibit a more rapid disease course in comparison with Christians. Further elucidation of population-specific MS phenotypes may contribute to improved disease management.

Medication habits among persons with multiple sclerosis.

BACKGROUND: Though habitual behavior is part of medication-taking behavior, studies of adherence to medication among persons with relapsing remitting multiple sclerosis (PwRRMS) have not prospectively examined habit in relation to disease-modifying treatments (DMTs). OBJECTIVES: 1. Examine habit dimensions - repetition, lack of awareness, and lack of control - across time and route of administration (oral vs. injectable). 2. Examine the association (prospective and cross sectional) of the dimension of repetition and the habit index with adherence and persistence in medication taking and to medication perceptions. METHODS: PwMS (n = 140), in their first year of treatment with a DMT, were prospectively assessed at three time points: at baseline, 6 months later (Time 1), and 12 months later (Time 2). Clinical and demographic information were obtained in-person, as were patient-reported medication habits and medication perceptions. Adherence and persistence were assessed with a combination of self-reporting and retrospective review of medication claims. RESULTS: Repeated measures analysis of variance (ANOVA), with dimension as the within-subject factor at each time point, indicated that the repetition dimensions at all points were significantly higher than lack of awareness and lack of control dimensions. Repeated measures ANOVA, with time as the within-subject factor and route of administration as between-subject factor, yielded a significant time effect in repetition and lack of awareness dimensions so that they increased across time but not in lack of control; administration route effects were found to be nonsignificant in all dimensions. Repetition at Time 1 was positively associated with patient-reported adherence at this time point (rs = 0.33, p = 0.002) but this was not consistently found at other time points . Likewise, reported repetition at Time 1 was higher among PwRMS who persisted with their medication a year later than among those who did not persist. Perceptions of medication (concern, harm, and overtreatment) were significantly negatively associated with reported repetition. CONCLUSIONS: Over time, PwRMS reported an increase in two habit dimensions, repetition and lack of awareness, in medication taking. No significant differences in habit by administration modality were found. The habit dimension of repetition was significantly associated with perceptions of medication, adherence, and prospectively predicted persistence. However, the low values obtained for lack of awareness and lack of control, compared with the higher levels of repetition, indicate that the habit is not well ingrained. Hence, intervention to target habit formation and maintenance, to be tailored to the individual, are a promising venue for enhancing medication adherence and improving disease outcomes.