Search

The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine whether women with MS experience increased relapse rates after delivery. A systematic literature search was conducted in the databases MEDLINE and Epistemonikos on the topic ‘motherhood choice in MS’ in March 2022. We included cohort studies assessing the association between pregnancy and MS relapse activity defined by the annualised relapse rate after 3, 6, 9 and 12 months post partum. Furthermore, information about disease-modifying therapies (DMT) and breast feeding was considered, if available. 5369 publications were identified. Of these, 93 full-text articles on MS relapse activity during the postpartum period were screened. 11 studies including 2739 pregnancies were eligible. Women with MS showed a significantly increased relapse rate in the first 6 months post partum, compared with preconception with the incidence rate ratio (IRR) almost doubled in the first 3 months post partum (1.87, 95% CI 1.40 to 2.50). However, at 10–12 months post partum, the IRR decreased significantly (0.81, 95% CI 0.67 to 0.98). Subanalysis on influencing parameters suggested that preconceptional DMTs (IRR for highly-effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. Increased postpartum annualised relapse rate and possible modifiers should be considered in counselling women with MS who are considering pregnancy.

IntroductionProgressive chronic, non-malignant diseases (CNMD) like congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia are of growing relevance in primary care. Most of these patients suffer from severe symptoms, reduced quality of life and increased numbers of hospitalisations. Outpatient palliative care can help to reduce hospitalisation rate by up to 50%. Due to the complex medical conditions and prognostic uncertainty of the course of CNMD, early interprofessional care planning among general practitioners who provide general palliative care and specialist palliative home care (SPHC) teams seems mandatory. The KOPAL study (a concept for strenghtening interprofessional collaboration for patients with palliative care needs) will test the effectiveness of a SPHC nurse–patient consultation followed by an interprofessional telephone case conference.Methods and analysisMulticentre two-arm cluster randomised controlled trial KOPAL with usual care as control arm. The study is located in Northern Germany and aims to recruit 616 patients in 56 GP practices (because of pandemic reasons reduced to 191 participants). Randomisation will take place on GP practice level immediately after inclusion (intervention group/control group). Allocation concealment is carried out on confirmation of participation. Patients diagnosed with CHF (New York Heart Association (NYHA) classification 3–4), COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage classification 3–4, group D) or dementia GDS stage 4 or above). Primary outcome is a reduced hospital admission within 48 weeks after baseline, secondary outcomes include symptom burden, quality of life and health costs. The primary analysis will follow the intention-to-treat principle. Intervention will be evaluated after the observation period using qualitative methods.Ethics and disseminationThe responsible ethics committees of the cooperating centres approved the study. All steps of data collection, quality assurance and data analysis will continuously be monitored. The concept of KOPAL could serve as a blueprint for other regions and meet the challenges of geographical equity in end-of-life care.Trial registration numberDRKS00017795; German Clinical Trials Register.

In the early phases of the UK COVID-19 outbreak, in the absence of clear evidence about the risks for people with multiple sclerosis (pwMS) and those taking immunomodulatory disease-modifying therapies (DMT), we launched a community-based study as part of the UK MS Register (UKMSR). We intended to capture the picture of COVID-19 among pwMS and their risk of contracting the disease. Here, we report our findings from 17 March to 24 April 2020. The COVID-19 study (clinicaltrials.gov:NCT04354519) is a prospective observational cohort launched on 17 March 2020 as part of the UKMSR (Ethics:16/SW/0194). PwMS completed a specific COVID-19 related survey which was combined with data held from before the pandemic where available. The primary outcome of the study is participant-reported self-diagnosis of COVID-19. Participants were asked if their diagnosis was confirmed by testing—the available test in the UK was reverse transcriptase-PCR. Participants reported if their sibling without MS, closest in age who was not living with them, had self-diagnosed COVID-19. The likelihood of having COVID-19 was assessed using multivariable regression analysis with the variables: age, gender, ethnicity, MS duration and type, self-isolation and DMTs. DMTs were considered after stratifying based on moderate-efficacy versus high-efficacy therapies (table 1). Disability was assessed using the last recorded web-based Expanded Disability Status Scale (webEDSS) or MS Impact Scale v2 (MSIS-29v2). View this table: Table 1 Distribution of individual disease-modifying therapies (DMTs) among participants of the COVID-19 study As of 24 April, out of 3910 participants, 237 (6.1% (95% CI 5.3% to 6.8%)) reported self-diagnosed COVID-19 among whom 54 (22.8% (17.5% to 28.2%)) also had a diagnosis by a healthcare professional based on symptoms and 37 (15.6% (11.2% to 20.6%)) a confirmed diagnosis by testing. Three participants reported hospitalisation due to COVID-19. No deaths were reported. Among 1283 siblings without MS, 79 (6.2%) had a reported diagnosis of COVID-19. …

ObjectiveFatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS.MethodsPatients with MS and self-reported fatigue were recruited via the website of the German MS Society and assigned via an automated randomisation generator (1:1, no blocking or stratification) to a 12-week online intervention (ELEVIDA, n=139, 82% female, mean age 40.8, median patient determined disease steps (PDDS) 3.0) or a waitlist control group (n=136, 79% female, mean age 41.9, median PDDS 3.0). The primary outcome was the Chalder Fatigue Scale. Outcomes were assessed at baseline, at week 12 (postintervention) and at follow-up (week 24).ResultsCompared with the control group, significantly greater reductions in Chalder Fatigue Scale scores were seen in the ELEVIDA group at week 12 (primary endpoint, intention-to-treat analysis: between-group mean difference 2.74 points; 95% CI 1.16 to 4.32; p=0.0007; effect size d=0.53), with effects sustained at week 24 (intention-to-treat analysis: between-group mean difference 2.19 points; 95% CI 0.57 to 3.82; p=0.0080).ConclusionsOur trial provides evidence for the effectiveness of a self-guided , internet-based intervention to reduce fatigue in MS. Interventions such as ELEVIDA may be a suitable low barrier, cost-effective treatment option for MS fatigue.Trial registration numberISRCTN registry (number ISRCTN25692173).

BackgroundIn long-term neurological conditions, location of death is poorly understood but is seen as a marker of quality of dying.ObjectiveTo examine individual, illness and environmental factors on place of death among people with multiple sclerosis (MS) and Parkinson’s disease (PD) in isolation or in combination and compare them with people without either condition.MethodsRetrospective, observational, comparative cohort study of 582 people with MS, 579 people with PD and 95 controls from UK Multiple Sclerosis and Parkinson’s Disease Tissue Bank. A subset of people with MS and PD were selected for analysis of individual clinical encounters 2 years before death and further subset of all groups for analysis of impact of advance care planning (ACP) and recognition of dying.ResultsPeople with MS died more often (50.8%) in hospital than those with PD (35.3%). Examining individual clinical encounters over 2 years (4931 encounters) identified increased contact with services 12 months before death (F(1, 58)=69.71, pF(1, 58)=1.001, p=0.321). The presence of ACPs and recognition of dying were high among people with MS and PD and both associated with a non-hospital death. ACPs were more likely to prevent hospital deaths when initiated by general practitioners (GPs) compared with other professional groups (χ2=68.77, p=0.0007).ConclusionsFor people with MS and PD, ACPs contribute to reducing dying in hospital. ACPs appear to be most effective when facilitated by GPs underlining the importance of primary care involvement in delivering holistic care at the end of life.

ObjectiveTo investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsWe performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.ResultsThe SFE significantly reduced the median number of monthly CELs from 1.00 (IQR 0.75–3.38) to 0.50 (IQR 0.00–1.13; difference −0.625, 95% CI −1.25 to −0.50; PInterpretationThe oral SFE was safe, tolerated well and exhibited beneficial effects on RRMS disease activity warranting further investigation in a controlled phase IIb or III trial.Clinical trial registrationNCT01450124; Results.

IntroductionMultiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system that mainly affects young adults. Uncertainty is a major psychological burden of the disease from diagnosis to prognosis, enhanced by the pressure to make early decisions on a diverse set of immunotherapies. Watchful waiting for 1–2 years while adapting goals and lifestyle habits to life with a chronic disease represents another reasonable option for persons with MS (PwMS). A behaviour change programme based on evidence-based patient information (EBPI) is not available in standard care. This randomised controlled trial (RCT) with an embedded process evaluation investigates the efficacy and cost-effectiveness of a web-based behavioural lifestyle programme to change lifestyle behaviour and reduce inflammatory disease activity in PwMS.Methods and analysisA web-based behavioural intervention will be evaluated in an RCT aiming to recruit 328 persons with clinically isolated syndrome, suspected MS or confirmed MS for less than 1 year, who have not yet started immunotherapy. Moreover, a mixed-methods process evaluation and a health economic evaluation will be carried out. Participants will be recruited in at least 16 MS centres across Germany and randomised to an intervention group with 12 months of access to EBPI about lifestyle factors in MS, combined with a complex behaviour change programme or to a control group (optimised standard care). The combined primary endpoint is the incidence of new T2 lesions on MRI or confirmed relapses.Ethics and disseminationThe study has been approved by the Ethics Committee of the Hamburg Chamber of Physicians (PV6015). Trial results will be communicated at scientific conferences and meetings and presented on relevant patient websites and in patient education seminars.Trial registration numberClinicalTrials.gov Registry (NCT03968172); Pre-results.

Objectives The main objective of the present study is to study the therapeutic efficiency of doxycycline in a double-blinded randomised phase II study in a cohort of patients with sporadic Creutzfeldt-Jakob disease (sCJD). Methods From the National Reference Center of TSE Surveillance in Germany, patients with probable or definite sCJD were recruited for a double-blinded randomised study with oral doxycycline (EudraCT 2006-003934-14). In addition, we analysed the data from patients with CJD who received compassionate treatment with doxycycline in a separate group. Potential factors which influence survival such as age at onset, gender, codon 129 polymorphism and cognitive functions were evaluated. The primary outcome measure was survival. Results Group 1: in the double-blinded randomised phase II study, 7 patients in the treatment group were compared with 5 controls. Group 2: 55 patients with sCJD treated with oral doxycycline were analysed and compared with 33 controls by a stratified propensity score applied to a Cox proportional hazard analysis. The results of both studies were combined by means of a random-effects meta-analysis. A slight increase in survival time in the doxycycline treatment group was observed (p=0.049, HR=0.63 (95% CI 0.402 to 0.999)). Conclusions On the basis of our studies, a larger trial of doxycycline should be performed in persons in the earliest stages of CJD. Trial registration number EudraCT 2006-003934-14; Results.

Objectives: To explore the impact of a community neonatal service on high risk infant survivors in the first year of life. Design: Retrospective multicentre survey. Postal questionnaires were sent to selected parents. Setting: Thirty two neonatal units in England and Wales. Patients: Inclusion criteria: infants over 12 months of age with birth weight