Use of cannabis to alleviate multiple sclerosis (MS)-related symptoms is increasing. Due to strict regulations, only a minority of MS patients receive cannabis-based prescription drugs. The extent of ...recreational and medical cannabis use among Danes with MS is unknown. Our aim was to evaluate the prevalence of illegal and legal use of cannabis in MS patients, as well as reasons for use and perceived adverse effects.
An anonymous questionnaire was sent to all 3606 patients at the Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen. The questionnaire included questions about sociodemographic factors, clinical characteristics and medical or recreational cannabis use.
Questionnaires were completed by 2244/3606 (62%), of which 2009 questionnaires from patients with MS or clinical isolated syndrome (CIS) were valid for analysis. Forty-nine percent (980/2009) had used cannabis at least once. Cannabis was used within the past year (current user) by 21%, and only 21% of those received prescribed cannabis-based medicine. Recreational use was reported by 17%. The primary reasons for use were to alleviate pain (61%), spasticity (52%) and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%) and dizziness (13%). Almost half (44%) of the non-cannabis users would consider use of cannabis to alleviate MS symptoms if the drug was legalized.
This study shows that illegal cannabis use is common among Danes with MS as only 21% of the current cannabis users received prescribed cannabis-based medicine. Current cannabis users reported high efficacy in relieving pain, spasticity and sleep disturbances. In addition, only mild to moderate severity of adverse effects were reported. To the best of our knowledge, this is the most comprehensive survey of cannabis use among MS patients.
Background
Gender appears to play a role in incidence and disease course of multiple sclerosis (MS).
Objective
The objective was to determine whether male and female patients with MS respond ...differently to interferon‐beta treatment in terms of reduction in relapse rates.
Methods
We included all 2033 patients with relapsing–remitting MS who started treatment with interferon‐beta from 1996 to 2003, identified from the Danish Multiple Sclerosis Treatment Register. We defined neutralizing antibody (NAb)‐positive and NAb‐negative periods in the single patient by the results of the NAb tests. Patients served as their own controls, and relapse rates were compared between NAb‐negative and NAb‐positive periods.
Results
NAbs significantly abrogated the interferon‐beta treatment efficacy in both genders. The all‐over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.28–1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women.
Conclusion
As NAbs influenced the on‐treatment relapse rates strongly in both sexes but without statistical significant difference, there is no indication of different effects of interferon‐beta in men or women.
Previous studies in multiple sclerosis (MS) showed that therapeutic inertia (TI) affects 60-90% of neurologists and up to 25% of daily treatment decisions. The objective of this study was to ...determine the most common factors and attribute levels associated with decisions to treatment escalation in an international study in MS care.
300 neurologists with MS expertise from 20 countries were invited to participate. Participants were presented with 12 pairs of simulated MS patient profiles described by 13 clinically relevant factors. We used disaggregated discrete choice experiments to estimate the weight of factors and attributes affecting physicians' decisions when considering treatment selection. Participants were asked to select the ideal candidate for treatment escalation from modest to higher-efficacy therapies.
Overall, 229 neurologists completed the study (completion rate: 76.3%). The top 3 weighted factors associated with treatment escalation were: previous relapses (20%), baseline expanded disability status scale EDSS (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (≤ 3%). We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-MS specialists.
Our results provide critical information on factors influencing neurologists' treatment decisions and should be applied to continuing medical education strategies.
Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The difference in the association of these national strategies with clinical outcomes ...is unknown.
To investigate the association of national differences in disease-modifying treatment (DMT) strategies for RRMS with disability outcomes.
This cohort study used data on 4861 patients from the Danish and Swedish national multiple sclerosis (MS) registries from the date of index DMT initiation (between January 1, 2013, and December 31, 2016) until the last recorded visit at time of data extraction (October 2, 2019).
All MS-specific DMTs initiated during the observation period were included in the analysis.
The primary study outcome was time to 24-week confirmed disability worsening. Secondary outcomes were 24-week confirmed disability improvement, milestone Expanded Disability Status Scale scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switching. Data were analyzed using inverse probability of treatment weighting-based models using a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the 2 countries.
A total of 2700 patients from the Swedish MS registry (1867 women 69.2%; mean SD age, 36.1 9.5 years) and 2161 patients from the Danish MS registry (1472 women 68.1%; mean SD age, 37.3 9.4 years) started a first DMT between 2013 and 2016, were included in the analysis, and were observed for a mean (SD) of 4.1 (1.5) years. A total of 1994 Danish patients (92.3%) initiated a low to moderately effective DMT (teriflunomide, 907 42.0%) and 165 (7.6%) initiated a highly effective DMT, whereas a total of 1769 Swedish patients (65.5%) initiated a low to moderately effective DMT (teriflunomide, 64 2.4%) and 931 (34.5%) initiated a highly effective DMT. The Swedish treatment strategy was associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (hazard ratio, 0.71; 95% CI, 0.57-0.90; P = .004). The Swedish treatment strategy was also associated with a 24% reduction in the rate of reaching an expanded disability status scale score of 3 (hazard ratio, 0.76; 95% CI, 0.60-0.97; P = .03) and a 25% reduction in the rate of reaching an expanded disability status scale score of 4 (hazard ratio, 0.75; 95% CI, 0.61-0.96; P = .01) relative to Danish patients.
The findings of this study suggest that there is an association between differences in treatment strategies for RRMS and disability outcomes at a national level. Escalation of treatment efficacy was inferior to using more efficacious DMT as initial treatment.
Since the last epidemiologic review of neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), 22 additional studies have been conducted. We systematically review the worldwide ...prevalence, incidence, and basic demographic characteristics of NMOSD and provide a critical overview of studies.
PubMed, Ovid MEDLINE, and Embase using Medical Subject Headings and keyword search terms and reference lists of retrieved articles were searched from 1999 until August 2019. We collected data on the country; region; methods of case assessment and aquaporin-4 antibody (AQP4-Ab) test; study period; limitations; incidence (per 100,000 person-years); prevalence (per 100,000 persons); and age-, sex-, and ethnic group-specific incidence or prevalence.
We identified 33 relevant articles. The results indicated the highest estimates of incidence and prevalence of NMOSD in Afro-Caribbean region (0.73/100 000 person-years 95% CI: 0.45-1.01 and 10/100 000 persons 95% CI: 6.8-13.2). The lowest incidence and prevalence of NMOSD were found in Australia and New Zealand (0.037/100 000 person-years 95% CI: 0.036-0.038 and 0.7/100,000 persons 95% CI: 0.66-0.74). There was prominent female predominance in adults and the AQP4-Ab-seropositive subpopulation. The incidence and prevalence peaked in middle-aged adults. African ethnicity had the highest incidence and prevalence of NMOSD, whereas White ethnicity had the lowest. No remarkable trend of incidence was described over time.
NMOSD is a rare disease worldwide. Variations in prevalence and incidence have been described among different geographic areas and ethnicities. These are only partially explained by different study methods and NMO/NMOSD definitions, highlighting the need for specifically designed epidemiologic studies to identify genetic effects and etiologic factors.
Background: Many studies have examined the relationship between physical activity and metabolic disorders. However, few have focused on specific associations between these disorders and muscular ...strengthening activity (MSA) patterns. The aim of the present study was to examine the association(s) for each metabolic syndrome criterion and MSA patterns.
Methods: The study sample (n = 5618) consisted of adults ≥20 years of age who participated in the 1999–2004 National Health and Nutrition Examination Survey. Cut‐off points for metabolic syndrome criteria were derived from the American Heart Association/National Heart, Lung, and Blood Institute definition. The aggregate of data on weight lifting, push‐ups, and sit‐ups was used to establish patterns of MSA. Participants reporting ≥2 days/week MSA were coded as meeting current US MSA guidelines.
Results: Following adjustments, participants reporting ≥2 days/week MSA were found to be 28% (OR 0.72; 95% CI 0.62, 0.83) less likely to have dyslipidemia, 29% (OR 0.71; 95% CI 0.54, 0.93) less likely to have impaired fasting glucose, 19% (OR 0.81; 95% CI 0.65, 0.99) less likely to have prehypertension, and 43% (OR 0.57; 95% CI 0.46, 0.72) less likely to have augmented waist circumference compared with those reporting engaging in no MSA. No association was found for hypertension and MSA.
Conclusion: Engaging in ≥2 days/week MSA as part of an overall physical activity regimen may be prudent in preserving metabolic health. These findings strengthen the relationship between MSA and metabolic health; thus, clinicians should include MSA when discussing lifestyle approaches to better health.
Epidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors ...may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15-19 years.
The aim of this study was to investigate the association between shift work at young age and the risk of developing MS.
We performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15-19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors.
We found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08-1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01-1.06, p=0.002). Duration of shift work in years was not associated with risk of MS.
This study supports a statistically significant association between shift work at age 15-19 years and MS risk.
Background:
The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.
Objective:
The aim of ...this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.
Methods:
Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.
Results:
A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients’ group.
Conclusion:
Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined ...the characteristics of COVID-19 severity in an international sample of people with MS.
Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score.
Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio aOR 1.56, 95% confidence interval CI 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02) and ICU admission (aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07) and ICU admission (aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92) and ICU admission (aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71-17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.
Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.
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