Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO‐NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease‐modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end‐of‐life management.Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

Mobile Health (mHealth) refers to using mobile devices to support health. This study aimed to identify specific methodological challenges in systematic reviews (SRs) of mHealth interventions and to develop guidance for addressing selected challenges. Two-phase participatory research project. First, we sent an online survey to corresponding authors of SRs of mHealth interventions. On a five-category scale, survey respondents rated how challenging they found 24 methodological aspects in SRs of mHealth interventions compared to non-mHealth intervention SRs. Second, a subset of survey respondents participated in an online workshop to discuss recommendations to address the most challenging methodological aspects identified in the survey. Finally, consensus-based recommendations were developed based on the workshop discussion and subsequent interaction via email with the workshop participants and two external mHealth SR authors. We contacted 953 corresponding authors of mHealth intervention SRs, of whom 50 (5 %) completed the survey. All the respondents identified at least one methodological aspect as more or much more challenging in mHealth intervention SRs than in non-mHealth SRs. A median of 11 (IQR 7.25-15) out of 24 aspects (46 %) were rated as more or much more challenging. Those most frequently reported were: defining intervention intensity and components (85 %), extracting mHealth intervention details (71 %), dealing with dynamic research with evolving interventions (70 %), assessing intervention integrity (69 %), defining the intervention (66 %) and maintaining an updated review (65 %). Eleven survey respondents participated in the workshop (five had authored more than three mHealth SRs). Eighteen consensus-based recommendations were developed to address issues related to mHealth intervention integrity and to keep mHealth SRs up to date. mHealth SRs present specific methodological challenges compared to non-mHealth interventions, particularly related to intervention integrity and keeping SRs current. Our recommendations for addressing these challenges can improve mHealth SRs.

Randomized controlled trials (RCTs) are more likely to be included in evidence syntheses of health interventions due to their methodological rigor. However, the integration of nonrandomized studies (NRSs) may be necessary, as was seen during the COVID-19 pandemic due to the emergence of variants of concern. We aimed to examine the body of evidence, randomized and nonrandomized, on COVID-19 vaccine effectiveness (VE) during the emergence of the Delta variant and to share lessons learned from including nonrandomized evidence alongside randomized evidence in the COVID-NMA living systematic review. The COVID-NMA initiative is an international, living systematic review and meta-analysis that continually synthesized evidence on COVID-19 interventions. For this study, we identified all RCTs and comparative NRSs reporting on VE against the Delta variant from December 2020 (its initial detection) through November 2021 (date of last COVID-NMA NRS search). We conducted two parallel systematic reviews: one focusing on RCTs and the other on NRSs to compare available evidence on VE against the Delta variant. We also compared the publication timelines of the included studies with the global prevalence of the Delta variant, and documented the specific methodological challenges and solutions when including NRSs in living systematic reviews. From December 2020 to November 2021, only one RCT reported vaccine efficacy against Delta in a subgroup of 6325 participants, while, during the same period, 52 NRSs including 68,010,961 participants reported VE against this variant. Nevertheless, including NRSs in our living systematic review posed several challenges. We faced difficulties in identifying eligible studies, encountered overlapping studies (ie, NRSs using the same database), and inconsistent definitions of Delta variant cases. Moreover, multiple analyses and metrics for the same outcome were reported without a pre-specified primary analysis in a registry or protocol. In addition, assessing the risk of bias required expertise, standardization, and training. To remain responsive during public health emergencies, living systematic reviews should implement processes that enable the timely identification, evaluation, and integration of both randomized and nonrandomized evidence where appropriate. When new health treatments are tested, the best way to see how well they work is through randomized controlled trials (RCTs). These are carefully designed studies that help reduce bias. However, during the COVID-19 pandemic, scientists also had to rely on other types of studies called nonrandomized studies (NRS) based on real-world data because the virus was changing quickly and required urgent action. Our living systematic review examined how effective COVID-19 vaccines were against the Delta variant, which spread widely from late 2020 to 2021. We wanted to understand what both RCTs and NRSs revealed about vaccine protection at that time. We also aimed to learn about the benefits and challenges of including different kinds of studies. From December 2020 to November 2021, we found that only one RCT reported results specifically for the Delta variant, including just over 6000 people. However, during the same period, 52 NRSs, involving over 68 million people, shared results about vaccine effectiveness against Delta in real-world settings. Including these NRSs were important for answering questions quickly, but it also created challenges. For instance, it was sometimes unclear how studies should be included, as many used the same data sources. Different studies defined "Delta cases" in various ways and often reported several kinds of results without stating which one was most significant. Evaluating the quality of these studies was complex and required special training. We developed rules to handle each of these challenges. In this study, we found that while RCTs remain the gold standard, NRSs provided crucial information during a fast-moving public health emergency. To help patients, doctors, and policymakers get timely answers in the future, living systematic reviews should be designed to include both types of evidence when appropriate, using clear methods to address challenges.

Background: Increasing numbers of young people with severe neurological impairment are suffering from gastrointestinal symptoms, which may result in nutritional failure and ultimately death. Gastrointestinal dystonia is a recently described clinical diagnosis amongst patients with severe neurological impairment, and no systematic review of existing evidence currently exists. Aim: To conduct a systematic review of existing evidence for the management of gastrointestinal dystonia in children and young people with severe neurological impairment and palliative care needs. Method: A systematic review assessing pharmacological and non-pharmacological treatments was undertaken using standard Cochrane methodology. We searched Cochrane CENTRAL, MEDLINE, EMBASE, and PsycInfo. All databases were searched from inception, and no language restrictions were used. Results: 1580 references were identified. After abstract screening, 56 references were reviewed at full text, and a case report and case series were identified for inclusion. Low-quality, indirect evidence exists for the management of gastrointestinal dystonia, including symptom management, hydration and nutrition decisions, and end-of-life care. Conclusions: There is a paucity of existing evidence directly relating to gastrointestinal dystonia, but low-quality indirect evidence from studies of children with severe neurological impairment and gastrointestinal symptoms exist, which may begin to inform clinical practice.

The 2026 Bundibugyo virus disease (BVD) outbreak in DRC and Uganda underscores that filoviruses remain an unpredictable global health threat, particularly in resource-limited settings. The sporadic occurrence of outbreaks has constrained evidence-generation. We implemented a Rapid Research Needs Appraisal (RRNA) to rapidly and systematically synthesise published research evidence and identify gaps in the evidence base to support management and research strategies. We searched Ovid Medline, Embase and Scopus for primary research studies published between Jan 1, 1999, and Feb 6, 2026 by combining keywords and thesaurus headings for Bundibugyo and humans. This search was supplemented by an updated search in PubMed and MedRxiv up to June 25, 2026. Searches were conducted in English, but without language restrictions. Eligible studies including humans or human samples focused on at least one of the RRNA domains (clinical characteristics, immune response, transmission, risk factors, medical countermeasures and associated social and behavioural factors). Two reviewers screened records for inclusion, one reviewer extracted data with a second reviewer checking a proportion of the data. Data were analysed descriptively. 29 primary studies were eligible for inclusion, accounting for 1593 probable or confirmed BVD cases. Of these 29 studies, most were observational (n = 28, 96.6%) and were most commonly conducted in Uganda (n = 15, 51.7%) and the DRC (n = 10, 34.5%). Only one interventional study was included, a non-randomized interventional study exploring EBOV, SUDV and BDBV cross-reactivity following EBOV vaccination. Among studies that reported age, most (58.6%, 17/29) included adults (18+ years), eight (27.6%) included children (0-18 years), and only two (6.9%) included pregnant women. Fever, vomiting, diarrhoea, headache, fatigue, dysphagia, anorexia, dyspnoea and abdominal pain were the most commonly reported symptoms. Haemorrhagic manifestations ranged from 10.4 to 54.0%, with a meta-analysis estimating a CFR of 32.8% (CI 25.8-40.2) based on past outbreaks. Evidence on cross-reactivity to previous Ebola exposure following natural infection of vaccination was sparse and conflicting. One study identified low levels of cross-reactivity in EBOV vaccinated participants, another among EBOV survivors, whereas a third did not detect cross-reactivity following EBOV vaccination. Long-term sequelae, persistent BVD survivor stigma and limited community awareness were also reported. Whilst acknowledging the limitations of such a rapid appraisal, our findings show that urgent, coordinated investment is needed in countermeasure trials inclusive of pregnant women and children, supported by observational studies community engagement and co-production. The National Institute for Health Research (NIHR) and the Wellcome Trust.