The incidence of multiple sclerosis is increasing in Danish women. Their risk of developing multiple sclerosis has more than doubled in 25 years while it has remained virtually unchanged for men. The ...explanation for these epidemiological changes should be sought in the environment as they are too rapid to be explained by gene alterations. We investigated the effect of numerous biological social physical and chemical environmental exposures in different periods of life. These data were available from population‐based registries and were used in a case–control approach. This study database included all multiple sclerosis cases (n = 1403) from the Danish MS Registry with clinical onset between 2000 and 2004 as well as 35,045 controls drawn by random from the Danish Civil Registration System and matched by sex year of birth and residential municipality at the reference year. Having newborn children reduced the risk of multiple sclerosis (MS) in women but not in men. Childbirths reduced the risk of MS by about 46% during the following 5 years. Even pregnancies terminated early had a protective effect on the risk of developing MS suggesting a temporary immunosuppression during pregnancy. Our data on social behaviour regarding educational level income and relationship stability did not indicate reverse causality. A greater likelihood to be exposed to common infections did not show any effect on the risk of MS neither in puberty nor in adulthood. Socio‐economic status and lifestyle expressed in educational level and sanitary conditions in youth were not associated with the risk of MS.
Background and purpose
To assess long‐term treatment effectiveness of disease‐modifying therapy (DMT) initiated early in disease course versus later treatment start.
Methods
We included all Danish ...patients with multiple sclerosis (MS) treated with DMT through two nationwide population‐based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted.
Results
The median follow‐up time of 3795 patients was 7.0 (range 0.6–19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2–20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early‐treated patients HR, 1.42; 95% confidence interval (CI), 1.18–1.70; P < 0.001. When stratified by sex, the increased hazard among later‐treated women persisted (HR, 1.53; 95% CI, 1.22–1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93–1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96–1.99; P = 0.08).
Conclusions
Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.
Abstract
STUDY QUESTION
Is female infertility among women seeking medically assisted reproduction (MAR) associated with prevalent as well as incident multiple sclerosis (MS)?
SUMMARY ANSWER
Women ...with a record of female infertility did not have an increased risk of developing MS compared with apparent fertile women; however, the prevalence of MS was slightly higher among women undergoing MAR compared with women who had a child without MAR, but this was not related to origin of infertility (i.e. male versus female factor infertility).
WHAT IS KNOWN ALREADY
Women with MS have fewer children compared with women without MS. Persons with MS more often have other coexisting autoimmune disorders including hypothyroidism compared with the general population. Thyroid dysfunction is associated with ovarian cause of infertility, miscarriage and ovarian failure. Conversely, women with endometriosis, that is highly associated with infertility, also more often have other coexisting autoimmune diseases including MS and hypothyroidism compared with the general population. However, whether the low fertility rate among women with MS is due to a genetically predisposition to other autoimmune and endocrine disorders that leads to reduced fertility, or an active choice of the woman, disease-related pathology or treatment-specific effect on endocrine and/or ovarian function, is not completely understood.
STUDY DESIGN, SIZE, DURATION
A register-based cohort study of a total of 310 357 women from 1996 to 2018. A cross-sectional design was used for analysing prevalence of MS, whereas a cohort design with up to 24 years of follow-up was used for analysing incidence of MS.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Three cohorts were included in the study (i) 55 404 women with a female infertility diagnosis registered in the Danish IVF register; (ii) 25 096 women with only male factor infertility recorded in the IVF register and thus no female infertility diagnosis and (iii) 229 857 age- and calendar-matched women with a record of first child birth in the Danish Medical Birth Register (DMBR) and no record ever in the IVF register. The prevalence and incidence of MS in the female infertility cohort were compared with the two control cohorts of apparent fertile women using log-binomial regression and Cox proportional hazard regression, respectively.
MAIN RESULTS AND THE ROLE OF CHANCE
The crude prevalence of having MS per 1000 persons was 3.2 for women who had undergone MAR treatment regardless of origin of infertility (i.e. male versus female factor infertility) and 2.3 for fertile DMBR controls. The age, calendar and educational level adjusted prevalence ratio of having a diagnosis of MS at the first MAR treatment was 1.27 (95% CI 1.07–1.52) for infertile women compared with fertile DMBR controls, and 1.00 (95% CI 0.77–1.31) for comparison to women with a male partner with infertility who had also undergone MAR treatment. We found no association between incident MS and female infertility compared with either of the control groups of fertile women.
LIMITATIONS, REASON FOR CAUTION
The cohort of infertile women is highly selected on the basis of their choice of having fertility treatment and thus does not include women with unestablished infertility or women who, for some reason, have chosen not to have MAR treatment. Additionally, due to the nature of the observational study design, we cannot exclude the possibility of unmeasured and/or residual confounding.
WIDER IMPLICATIONS OF THE FINDINGS
Our results suggest that women with MS may undergo MAR treatment more often than women without MS due to more awareness about the possibility of MAR treatments, sexual dysfunction related to MS disease, but also need for timing of the pregnancy to avoid an unnecessary long time period without disease modifying therapy—especially of high efficacy—and hence a wish to conceive quickly. These findings are important for clinicians dealing with women with MS of childbearing age.
STUDY FUNDING/COMPETING INTEREST(S)
The authors received no financial support for the study. T.I.K. has served on a scientific advisory board for Novartis and has received support for congress participation from Biogen. M.M. has served on scientific advisory boards for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie and Alexion. She has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi and Genzyme and has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck and Novartis. The remaining authors declare no conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Registers of multiple sclerosis in Denmark Koch-Henriksen, N.; Magyari, M.; Laursen, B.
Acta neurologica Scandinavica,
July 2015, Letnik:
132, Številka:
S199
Journal Article
Recenzirano
Odprti dostop
There are two nationwide population‐based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register ...for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier in life that may affect the risk of MS. This register has no systematic follow‐up data except for survival. The DMSR has over the years published nationwide incidence‐ and prevalence data from Denmark and has been involved in a number of ‘historical prospective’ studies to elucidate the association between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow‐up register for all patients who have received disease‐modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS.
Background and purpose
The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO ...Diagnosis (IPND) criteria.
Methods
A retrospective population‐based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re‐evaluation from multiple sources. Crude and sex‐ and serostatus‐specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person‐years) from 2006 to 2015 were estimated and age‐adjusted rates were determined.
Results
Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 95% confidence interval (CI) 1.52–2.28 per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person‐years provided an incidence rate of 1.32 (95% CI 1.08–1.61) per 1 000 000 person‐years. Age‐adjusted prevalence was 1.87 (95% CI 1.56–2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98–1.46) per 1 000 000 person‐years.
Conclusions
In this first report of a large population‐based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.
•B-cell depletion therapy is widely used in patients with demyelinating diseases.•We analyzed risk of severe infections (requiring hospitalization) and herpes zoster virus infection in patients ...treated with anti-CD20 therapy.•In multivariable analyses treatment duration, EDSS scores and presence of comorbidity were independently associated with risk of severe infections.•Low lymphocyte counts were independently associated with risk of varicella zoster virus infection.
Anti-CD20 antibody therapy may be associated with an increased risk of infections. We therefore investigated risk factors for infection in patients with demyelinating diseases treated with anti-CD20 antibody therapy.
In this retrospective uncontrolled study, patients ever treated with anti-CD20 antibodies at an academic clinic were identified through the Danish Multiple Sclerosis Registry (DMSR). Data were collected from medical charts and the DMSR. We assessed occurrence of severe infections (requiring hospitalization), varicella zoster virus (VZV), major comorbidities and routine laboratory values for lymphocytes, IgG and IgM.
A total of 447 patients ever treated with anti-CD20 antibody therapy were identified; of these 416 with 649 patient years of follow-up were still under therapy. In this group, seven patients had VZV infections, and 16 patients had been hospitalized with infections during up to three years of follow-up on anti-CD20 therapy. Comorbidity was recorded in 80 patients. The risk of severe infection was associated with comorbidities, higher age, longer duration of treatment, and higher Expanded Disability Status Scale (EDSS) scores. In multivariable analyses treatment duration, EDSS scores and presence of comorbidity were independently associated with risk of severe infections. Serum concentrations of IgG and IgM decreased with increasing duration of therapy but were not associated with risk of severe infections. Patients with VZV infection had lower lymphocyte counts and lower serum concentrations of IgM. In multivariable analyses only lymphocyte counts were independently associated with risk of VZV infection.
In this retrospective study of patients treated with anti-CD20 antibodies, the risk of infections requiring hospitalization was independently associated with comorbidities, duration of treatment, and higher EDSS scores. Risk of VZV infection was independently associated with lymphopenia. Future studies investigating strategies for mitigating risk of infection in patients treated with anti-CD20 antibodies are warranted, especially for older patients, patients with higher levels of disability and for patients with a longer duration of treatment.
Introduction of disease modifying treatment may have increased the cancer incidence in multiple sclerosis patients. Our aim was to estimate the incidence of any cancer, malignant melanoma, ...nonmelanoma skin cancer, and female breast cancer, and cancer specific mortality in multiple sclerosis patients diagnosed in 1995-2015 i.e. after introduction of disease modifying treatment.
Linking various Danish medical registers, we compared observed cancer incidence and cancer-specific mortality in multiple sclerosis patients versus expected based on general population rates.
Among 10,752 multiple sclerosis patients, we identified 5.76 incident cancers per 1,000 person-years. The standardized incidence ratio was 0.98 (95% confidence interval CI, 0.90-1.06) for any cancer, 0.99 (95% CI, 0.84-1.15) for non-melanoma skin cancer, and 0.98 (95% CI, 0.81-1.18) for female breast cancer. For malignant melanoma, the standardized incidence ratio was 1.51 (95% CI, 1.13-1.98) for the entire period (1995-2015) but 1.16 (95% CI, 0.62-1.99) for 2005-2015. The overall mortality rate was 1.31 (95% CI, 1.09-1.53) per 1000 person-years with a standardized mortality ratio of 0.99 (95% CI, 0.83-1.17).
In this nationwide study, multiple sclerosis patients did not have increased cancer incidence or increased cancer-specific mortality. We observed an increased risk of malignant melanoma mainly attributed to increased risk in the first part of our study period.
Background and purpose
The social and economic consequences of comorbidity in multiple sclerosis (MS) are largely unexplored. Differences were investigated in income and in the rate of broken ...relationships between cases of MS with and without chronic comorbidity.
Methods
We conducted a nationwide cohort study including all incident cases of MS in Denmark with clinical MS onset between 1980 and 2005. The difference in income was investigated at MS onset and 5 and 10 years after MS onset. The difference in the rate of broken relationships was investigated in subjects who were in a relationship at MS onset or who entered a relationship after MS onset. We used logistic, multiple linear and Poisson regression analyses.
Results
Cases of MS with somatic comorbidity had increased odds of low incomes both 5 years {odds ratio (OR), 1.41 95% confidence interval (CI), 1.19–1.67; P < 0.0005} and 10 years OR, 1.37 (95% CI, 1.17–1.60); P < 0.0005 after MS onset. The odds of a low income with psychiatric comorbidity was increased 10 years after MS onset OR, 3.06 (95% CI, 1.47–6.37); P = 0.003. The rate of broken relationships was increased in cases of MS with any somatic comorbidity incidence rate ratio, 1.46 (95% CI, 1.32–1.61); P < 0.0005.
Conclusions
Our results underscore the burden of comorbidity in MS on patients, their partners and society.
OBJECTIVES: This investigation examined the effect of 6 months of high‐ or low‐intensity resistance exercise on muscular strength and endurance and stair climbing ability in adults aged 60 to 83.
...DESIGN: A randomized controlled trial.
SETTING: University of Florida Center for Exercise Science
PARTICIPANTS: Sixty‐two men and women completed the study protocol. Subjects were matched for strength and randomly assigned to a control (n = 16), low‐intensity (LEX, n = 24), or high‐intensity (HEX, n = 22) group.
INTERVENTION: Six months of progressive, whole‐body resistance training. Subjects trained at 50% of their one‐repetition maximum (1RM) for 13 repetitions (LEX) or 80% of 1RM for eight repetitions (HEX) three times per week for 24 weeks using resistance machines. One set each of 12 exercises was performed.
MEASUREMENTS: One‐repetition maximum was measured for eight different exercises. Muscular endurance was measured using leg press and chest press machines. Low back strength was measured using a lumbar extension machine. Stair climbing ability was assessed as the time to ascend one flight of stairs.
RESULTS: 1RM significantly increased for all exercises tested for the HEX and LEX groups (P≤ .050). The increases in total strength (sum of all eight 1RMs) were 17.2% and 17.8% for the LEX and HEX groups, respectively. Muscular endurance improved by 79.2% and 105.0% for the leg press, and 75.5% and 68.0% for the chest press for the LEX and HEX groups, respectively. The time to ascend one flight of stairs significantly decreased for both the LEX and HEX groups (P≤ .050). Lumbar extension strength increased by 62.6% and 39.5% for the LEX and HEX groups, respectively.
CONCLUSIONS: These data indicate that significant and similar improvements in strength, endurance, and stair climbing time can be obtained in older adults as a consequence of high‐ or low‐intensity resistance exercise training. These findings may have an effect on how resistance exercise is prescribed to older adults.
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