Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

Background and purpose: Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is therefore a need for a reference tool compiling current data to aid professionals in treatment decisions. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS. Methods: This guideline has been developed using the GRADE methodology and following the updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. Literature searches up to December 2016 were performed and the evidence is presented narratively and, when possible, combined in a fax: +34 93 2746084; e-mail: xavier.montalban@cem-cat.org) and for EAN: R. Gold, Department of Neurology, Ruhr University, St Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany (tel.: +49-234-509244; fax: +49-234-5092414; e-mail: ralf.gold@rub.de). This is a Continuing Medical Education article, and can be found with corresponding questions on the EAN website, LEARN section https://www.ean. org/CME.2714.0.html. Certificates for correctly answered questions will be issued by EAN directly, you simply have to be logged-in. With positive results, EAN recommends accreditation of 1 hour of CME, which may be claimed with the national body in charge of CME accreditation. This paper is being simultaneously published in European Journal of Neurology and Multiple Sclerosis Journal.[Correction added on 13 February 2018, after online and print publication: (a) The abstract has been updated and a conclusion section in now included; (b) Recommendation 4 and 7 has been amended, and an additional recommendation has been added after the latter]. meta-analysis. The quality of evidence was rated into four categories -very high, high, low and very low À according to the risk of bias. The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the riskÀbenefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 21 recommendations were agreed by the guideline working group members after three rounds of consensus. Conclusion: The present guideline, which includes descriptions of the evidence together with recommendations, will enable homogeneity of treatment decisions across Europe. © 2018 European Academy of Neurology and European Committee of Treatment of Research in Multiple SclerosisBackground and scope

BackgroundMost research on interventions to counter stigma and discrimination has focused on short-term outcomes and has been conducted in high-income settings.AimsTo synthesise what is known globally about effective interventions to reduce mental illness-based stigma and discrimination, in relation first to effectiveness in the medium and long term (minimum 4 weeks), and second to interventions in low- and middle-income countries (LMICs).MethodWe searched six databases from 1980 to 2013 and conducted a multi-language Google search for quantitative studies addressing the research questions. Effect sizes were calculated from eligible studies where possible, and narrative syntheses conducted. Subgroup analysis compared interventions with and without social contact.ResultsEighty studies (n = 422 653) were included in the review. For studies with medium or long-term follow-up (72, of which 21 had calculable effect sizes) median standardised mean differences were 0.54 for knowledge and −0.26 for stigmatising attitudes. Those containing social contact (direct or indirect) were not more effective than those without. The 11 LMIC studies were all from middle-income countries. Effect sizes were rarely calculable for behavioural outcomes or in LMIC studies.ConclusionsThere is modest evidence for the effectiveness of anti-stigma interventions beyond 4 weeks follow-up in terms of increasing knowledge and reducing stigmatising attitudes. Evidence does not support the view that social contact is the more effective type of intervention for improving attitudes in the medium to long term. Methodologically strong research is needed on which to base decisions on investment in stigma-reducing interventions.

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Background and objectivesClinical responsiveness to cognitive behavioural therapy for psychosis (CBTp) varies. Recent research has demonstrated that illness perceptions predict active engagement in therapy, and, thereby, better outcomes. In this study, we aimed to investigate the psychometric properties of a modification of the Illness Perceptions Questionnaire (M-IPQ) designed to predict response following CBTp.MethodsFifty-six participants with persistent, distressing delusions completed the M-IPQ; forty before a brief CBT intervention targeting persecutory ideation and sixteen before and after a control condition. Additional predictors of outcome (delusional conviction, symptom severity and belief inflexibility) were assessed at baseline. Outcomes were assessed at baseline and at follow-up four to eight weeks later.ResultsThe M-IPQ comprised two factors measuring problem duration and therapy-specific perceptions of Cure/Control. Associated subscales, formed by summing the relevant items for each factor, were reliable in their structure. The Cure/Control subscale was also reliable over time; showed convergent validity with other predictors of outcome; predicted therapy outcomes; and differentially predicted treatment effects.LimitationsWe measured outcome without an associated measure of engagement, in a small sample. Findings are consistent with hypothesis and existing research, but require replication in a larger, purposively recruited sample.ConclusionsThe Cure/Control subscale of the M-IPQ shows promise as a predictor of response to therapy. Specifically targeting these illness perceptions in the early stages of cognitive behavioural therapy may improve engagement and, consequently, outcomes.

Background: The use of observational measures to assess palliative care patients’ level of consciousness may improve patient care and comfort. However, there is limited knowledge regarding the validity and reliability of these measures in palliative care settings. Aim: To identify and evaluate the psychometric performance of observational level of consciousness measures used in palliative care. Design: Systematic review; PROSPERO registration: CRD42017073080. Data sources: We searched six databases until November 2018, using search terms combining subject headings and free-text terms. Psychometric performance for each identified tool was appraised independently by two reviewers following established criteria for developing and evaluating health outcome measures. Results: We found 35 different levels of consciousness tools used in 65 studies. Only seven studies reported information about psychometric performance of just eight tools. All other studies used either ad hoc measures for which no formal validation had been undertaken ( n = 21) or established tools mainly developed and validated in non-palliative care settings ( n = 37). The Consciousness Scale for Palliative Care and a modified version of the Richmond Agitation–Sedation Scale received the highest ratings in our appraisal, but, since psychometric evidence was limited, no tool could be assessed for all psychometric properties. Conclusion: An increasing number of studies in palliative care are using observational measures of level of consciousness. However, only a few of these tools have been tested for their psychometric performance in that context. Future research in this area should validate and/or refine the existing measures, rather than developing new tools.

This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.

Background Primary sclerosing cholangitis (PSC) is a rare incurable disease of the bile ducts and liver which can significantly impair quality of life (QoL). No existing QoL tools are entirely suitable for people living with PSC (PwPSC). We aimed to develop a measure of QoL for PwPSC in the UK, beginning by identifying relevant QoL issues. This paper describes our approach to this first stage, and discusses related benefits and limitations. Methods Scientific consensus on how to reliably stage PSC is lacking, due to its rarity and heterogeneity. We initially hypothesised four categories for PSC severity. After beginning the study, these were revised to six. For such a rare disease, the study could not recruit sufficient participants in each of these categories, particularly the more severe, in the time available. We therefore modified the design, adapting standard methodology for identifying potentially relevant issues. We started by conducting a thematic analysis of data from a previous survey of PwPSC, and extracting QoL issues from a literature review of QoL questionnaires of relevance to PwPSC. We then conducted group and individual interviews with PwPSC and clinicians, investigating the relevance, importance, phrasing, and breadth of coverage of issues identified. We also explored the validity of our hypothesised categories for disease severity. Results We identified 1,052 potentially relevant QoL issues from the survey and literature review and took 396 of these forwards for discussion with 28 PwPSC. We found 168/396 issues were considered relevant by ≥ 60% of these participants. We then discussed this subset of 168 issues with 11 clinicians. PSC and clinician participants identified some problematic phrasing with 19 issues, due to potential upset (n = 12) or problems with understanding (n = 7). We included one new issue from those suggested. Conclusion We identified a range of QoL issues relevant to PwPSC, with a good breadth of coverage, although lacking an in-depth understanding of the PSC experience. Our strategy effectively identified relevant QoL issues for people living with this rare condition, for which there is no consensus on stratifying for its severity. This strategy should however be considered specific to such circumstances, not a general recommendation for an alternative approach.