Search

Introduction: Studies investigating risk factors for severe COVID-19 often lack information on the representativeness of the study population. Here, we investigate factors associated with severe COVID-19 and compare the representativeness of the dataset to the general population. Methods: We used data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) of hospitalized COVID-19 patients diagnosed in 2020 in Germany to identify associated factors for severe COVID-19, defined as progressing to a critical disease stage or death. To assess the representativeness, we compared the LEOSS cohort to cases of hospitalized patients in the German statutory notification data of the same time period. Descriptive methods and Poisson regression models were used. Results: Overall, 6672 hospitalized patients from LEOSS and 132,943 hospitalized cases from the German statutory notification data were included. In LEOSS, patients above 76 years were less likely represented (34.3% vs. 44.1%). Moreover, mortality was lower (14.3% vs. 21.5%) especially among age groups above 66 years. Factors associated with a severe COVID-19 disease course in LEOSS included increasing age, male sex (adjusted risk ratio (aRR) 1.69, 95% confidence interval (CI) 1.53–1.86), prior stem cell transplantation (aRR 2.27, 95% CI 1.53–3.38), and an elevated C-reactive protein at day of diagnosis (aRR 2.30, 95% CI 2.03–2.62). Conclusion: We identified a broad range of factors associated with severe COVID-19 progression. However, the results may be less applicable for persons above 66 years since they experienced lower mortality in the LEOSS dataset compared to the statutory notification data. [ABSTRACT FROM AUTHOR]

Objective: To investigate the time to diagnosis in multiple sclerosis (MS) in Germany. Methods: Analysis of real-world registry data from the German Multiple Sclerosis Registry (GMSR) and performing a primary analysis in patients where month-specific registration of the dates of onset and diagnosis was available. Results: As of January 2020, data of a total of 28,658 patients with MS were extracted from the GMSR, with 9836 patients included in the primary analysis. The mean time to diagnosis was shorter following the introduction of the first magnetic resonance imaging (MRI)-based McDonald criteria in 2001. This effect was most pronounced in younger adults below the age of 40 years with relapsing onset multiple sclerosis (ROMS), with a decrease from 1.9 years in 2010 to 0.9 years in 2020, while unchanged in patients aged 40–50 years (1.4 years in 2010 and 1.3 years in 2020). In the limited number of paediatric onset MS patients, the time to diagnosis was longer and did not change (2.9 years). Conclusion: The current sensitive MRI-based diagnostic criteria have likely contributed to an earlier diagnosis of MS in Germany in younger adults aged 18–39 years with ROMS. Whether this translated to earlier initiation of disease-modifying treatment or had a beneficial effect on patient outcomes remains to be demonstrated. [ABSTRACT FROM AUTHOR]

Objective: Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks.Methods: A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete remission [CR], partial remission [PR], no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient-based statistical approach.Results: A total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high-dose intravenous steroids (HD-S; n = 810), plasma exchange (PE; n = 192), immunoadsorption (IA; n = 38), other (n = 80), and unknown (n = 33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome (p < 0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis (p < 0.001), and for unilateral versus bilateral optic neuritis (p = 0.020). Isolated myelitis responded better to PE/IA than to HD-S as first treatment course (p = 0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR] = 0.97, p = 0.011), presence of myelitis (OR = 0.38, p = 0.002), CR from previous attack (OR = 6.85, p < 0.001), and first-line PE/IA versus HD-S (OR = 4.38, p = 0.006).Interpretation: Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis. [ABSTRACT FROM AUTHOR]

Objective: In some countries, such as Germany, there has been a move towards the treatment of patients with Parkinson’s disease in specialised inpatient units. However, data on patient outcome and the daily costs of antiparkinsonian drugs in these settings are rare. This study was conducted to determine the effect of an inpatient setting (a specialised Parkinson’s disease clinic) on drug therapy costs and patient symptoms. Patients and Methods: This study involved 63 consecutively referred inpatients of a Parkinson’s disease clinic. On entry to the clinic, the patients’ antiparkinsonian drug regimen was titrated in order to improve their motor function. The daily costs of drug therapy per patient (in 2002 values) were calculated, and the severity of Parkinson’s disease symptoms scored via scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) and standardised instrumental procedures (peg insertion and tapping), both initially and at the end of the patients’ stay in the clinic. The variables between the two evaluation timepoints were compared. Results: The titration of antiparkinsonian drugs was associated with a significant decrease in the symptoms of Parkinson’s disease at discharge from the clinic compared with admission (as measured by UPDRS total and subscale scores [all p < 0.001], and, to a lesser extent, by peg insertion and tapping [both p < 0.05]). A significant increase in daily drug costs (an increase of euro14.11 per patient for all drugs and euro12.36 per patient for antiparkinsonian drugs [both p <0.001]) was also observed. Conclusion: The results demonstrate that the symptoms experienced by patients with Parkinson’s disease improve after performance of antiparkinsonian drug titration within the setting of a specialised Parkinson’s disease clinic. The effect on symptoms was seen most clearly with the UPDRS, although both peg insertion and tapping reflected this improvement to a certain extent. Drug titration resulted in, on average, a doubling of daily drug costs. Future trials are needed to investigate the long-term effects of such a hospital stay on indirect costs associated with treating Parkinson’s disease, and on caregiver burden, and also to compare the efficacy of a Parkinson’s disease clinic with an outpatient setting. [ABSTRACT FROM AUTHOR]

Objective: To investigate the time to diagnosis in multiple sclerosis (MS) in Germany., Methods: Analysis of real-world registry data from the German Multiple Sclerosis Registry (GMSR) and performing a primary analysis in patients where month-specific registration of the dates of onset and diagnosis was available., Results: As of January 2020, data of a total of 28,658 patients with MS were extracted from the GMSR, with 9836 patients included in the primary analysis. The mean time to diagnosis was shorter following the introduction of the first magnetic resonance imaging (MRI)-based McDonald criteria in 2001. This effect was most pronounced in younger adults below the age of 40 years with relapsing onset multiple sclerosis (ROMS), with a decrease from 1.9 years in 2010 to 0.9 years in 2020, while unchanged in patients aged 40-50 years (1.4 years in 2010 and 1.3 years in 2020). In the limited number of paediatric onset MS patients, the time to diagnosis was longer and did not change (2.9 years)., Conclusion: The current sensitive MRI-based diagnostic criteria have likely contributed to an earlier diagnosis of MS in Germany in younger adults aged 18-39 years with ROMS. Whether this translated to earlier initiation of disease-modifying treatment or had a beneficial effect on patient outcomes remains to be demonstrated.

In 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry (GMSR) as a long-term data repository for MS healthcare research. By the establishment of a network of participating neurological centres of different healthcare sectors across Germany, GMSR provides observational real-world data on long-term disease progression, sociodemographic factors, treatment and the healthcare status of people with MS. This paper aims to illustrate the framework of the GMSR. Structure, design and data quality processes as well as collaborations of the GMSR are presented. The registry's dataset, status and results are discussed. As of 08 January 2021, 187 centres from different healthcare sectors participate in the GMSR. Following its infrastructure and dataset specification upgrades in 2014, more than 196,000 visits have been recorded relating to more than 33,000 persons with MS (PwMS). The GMSR enables monitoring of PwMS in Germany, supports scientific research projects, and collaborates with national and international MS data repositories and initiatives. With its recent pharmacovigilance extension, it aligns with EMA recommendations and helps to ensure early detection of therapy-related safety signals.

Objective: To report pregnancy outcomes and disease activity (DA) in women with MS, neuromyelitis optica spectrum disorders (NMOSDs), and other neuroimmunologic diseases (ONID) after treatment with rituximab (RTX)/ocrelizumab (OCR) 12 months before or during pregnancy., Methods: Data were collected in the German MS and pregnancy registry and centers from the Neuromyelitis Optica Study Group. Sixty-eight known outcomes of 88 pregnancies from 81 women (64 MS, 10 NMOSD, and 7 ONID) were included and stratified in 3 exposure groups: >6M-group = RTX/OCR >6 but ≤12 months before the last menstrual period (LMP) (n = 8); <6M group = RTX/OCR <6 months before the LMP (n = 47); preg group = RTX/OCR after the LMP (n = 13)., Results: Pregnancy outcomes were similar between groups, but significantly more preterm births (9.8% vs 45%) occurred after exposure during pregnancy. Overall, 2 major congenital abnormalities (3.3%), both in the preg group, were observed. Three women had severe infections during pregnancy. All women with MS (35) and 12/13 women with NMOSD, RTX/OCR exposure before the LMP and known pregnancy outcomes after gestational week 22 were relapse free during pregnancy. Five of 29 (17.2%) women with relapsing-remitting MS (RRMS) and 1 of 12 (8.3%) with NMOSD and at least 6 months postpartum follow-up experienced a relapse postpartum. Duration of RTX/OCR and early retreatment but not detection of B-cells were possible predictors for postpartum relapses in patients with RRMS/NMOSD., Conclusions: Although RTX/OCR might be an interesting option for women with RRMS/NMOSD who plan to become pregnant to control DA, more data on pregnancy outcomes and rare risks are needed., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: The incidence of multiple sclerosis (MS) is increasing, particularly in young women (20-40 years). In line, experience in the management of pregnancies and use of disease-modifying therapy (DMT) in women with MS is accumulating., Summary: Fertility is generally not affected in MS. If assisted reproduction techniques (ART) are required, unsuccessful procedures are associated with an increased relapse risk, particularly in the first few months post-ART. During pregnancy, the risk of relapse declines continuously, especially in the third trimester, then increases early postpartum (3 months) and returns to pre-pregnancy levels at 4-6 months. The progression of MS disability is probably not influenced by pregnancy. Obstetrical outcomes show no increased risk for miscarriage/malformations, and the course of pregnancy is similar to that of women without MS, but with a tendency towards assisted delivery/cesarean section and reduced birth weights. Safety data regarding DMT in pregnancy and breastfeeding are limited. Exclusive breastfeeding may be beneficial and, hence, should not be discouraged in favour of resuming DMT except in cases of highly-active disease. Key Messages: The course of pregnancy in women with MS is broadly similar to that in women without MS; risk-to-benefit assessments are warranted when considering halting DMT before pregnancy and resuming DMT postpartum., (© 2014 S. Karger AG, Basel.)

Importance: Given the high frequency of failure of first-line therapies, there is an urgent need for second-line treatment strategies for pediatric patients with multiple sclerosis (MS)., Objective: To report the use of natalizumab in pediatric MS. Natalizumab, a humanized monoclonal antibody targeting α4 integrin, is effective against active relapsing-remitting MS in adults., Design: Retrospective study., Setting: Eleven centers for neurology and pediatric neurology in Germany and Austria., Participants: A total of 20 pediatric patients with MS who started treatment with natalizumab prior to 18 years of age. These patients underwent magnetic resonance imaging as clinically indicated, despite the fact that 19 of these 20 patients were undergoing first-line disease-modifying therapy. The mean (SD) age at initiation of natalizumab therapy was 16.7 (1.1) years, and the mean (SD) pretreatment period was 18 (10) months., Intervention: Natalizumab, 300 mg every 4 weeks., Main Outcome Measures: Annualized relapse rates, Expanded Disability Status Scale scores, number of new T2/fluid-attenuated inversion recovery lesions and contrast-enhancing lesions on magnetic resonance imaging, number of adverse events, the prevalence of neutralizing antibodies against natalizumab, and serum JC virus-antibody status. RESULTS Treatment with natalizumab was associated with reductions in mean annualized relapse rates (3.7 without treatment vs 0.4 with treatment; P < .001), median Expanded Disability Status Scale scores (2 without treatment vs 1 with treatment; P < .02), and mean number of new T2/fluid-attenuated inversion recovery lesions per year (7.8 without treatment vs 0.5 with treatment; P < .001). Two patients developed high-titer neutralizing antibodies against natalizumab and had to stop therapy. Adverse events included headaches, asthenia, infections, and hypersensitivity. Abnormal laboratory results were found for 8 patients. JC virus antibodies were found in 5 of 13 patients. After the discontinuation of natalizumab therapy, relapse activity occurred in 6 of 8 patients within 6 months., Conclusions and Relevance: Our data indicate that natalizumab may be safe and effective against MS in pediatric patients with breakthrough disease.