This case elaborates how a simple 'nudge' of religious tenets-based counselling helps the tobacco addict transgress or tide over such barriers. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.We present a case of Sandifer syndrome in a 3-year-old girl who initially presented with a history of recurrent paroxysmal head drops associated with ataxia-like symptoms and recurrent falls sustaining a clavicular fracture on one occasion. She was referred to and seen by the paediatric neurologist. Physical examination, electroencephalogram, MRI brain, electromyograph single fibre study and blood tests were all normal. With the history of hiccups and choking-like episodes she was referred to the speech and language therapist (SALT). SALT assessment did not reveal indications of swallowing impairment or possible aspiration. A barium swallow later showed small amount of reflux into the distal oesophagus. This prompted a trial of lansoprazole and she was referral to the gastroenterologists. Endoscopy and oesophageal manometry were essentially normal. However, the pH impedance study revealed severe gastro-oesophageal reflux disease. She continued with lansoprazole and dairy-free diet and her symptoms resolved. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Here we present a rare combination of aortobronchial fistula and Listeria endograft infection after repeat endovascular aortic repair. Device retention, debridement and negative pressure wound therapy, in combination with suppressive antimicrobial therapy, led to satisfactory control of infection until the patient died due to another complication. The combination of an aortobronchial fistula and Listeria endograft infection has never been described before. This present case should encourage and show clinicians the importance of an interdisciplinary approach in highly difficult clinical courses. © BMJ Publishing Group Limited 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Meta-analyses of observational studies are frequently published in the literature, but they are generally considered suboptimal to those involving randomised controlled trials (RCTs) only. This is due to the increased risk of biases that observational studies may entail as well as because of the high heterogeneity that might be present. In this article, we highlight aspects of meta-analyses with observational studies that need more careful consideration in comparison to meta-analyses of RCTs. METHODS We present an overview of recommendations from the literature with respect to how the different steps of a meta-analysis involving observational studies should be comprehensively conducted. We focus more on issues arising at the step of the quantitative synthesis, in terms of handling heterogeneity and biases. We briefly describe some sophisticated synthesis methods, which may allow for more flexible modelling approaches than common meta-analysis models. We illustrate the issues encountered in the presence of observational studies using an example from mental health, which assesses the risk of myocardial infarction in antipsychotic drug users. RESULTS The increased heterogeneity observed among studies challenges the interpretation of the diamond, while the inclusion of short exposure studies may lead to an exaggerated risk for myocardial infarction in this population. https://www.selleckchem.com/products/ku-0060648.html CONCLUSIONS In the presence of observational study designs, prior to synthesis, investigators should carefully consider whether all studies at hand are able to answer the same clinical question. The potential for a quantitative synthesis should be guided through examination of the amount of clinical and methodological heterogeneity and assessment of possible biases. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. METHODS RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. RESULTS mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. CONCLUSION mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.OBJECTIVE To establish cytometry profiles associated with disease stages and immunotherapy in MS. METHODS Demographic/clinical data and peripheral blood samples were collected from 227 patients with MS and 82 sex- and age-matched healthy controls (HCs) enrolled in a cross-sectional study at 4 European MS centers (Spain, Italy, Germany, and Norway). Flow cytometry of isolated peripheral blood mononuclear cells was performed in each center using specifically prepared antibody-cocktail Lyotubes; data analysis was centralized at the Genoa center. Differences in immune cell subsets were assessed between groups of untreated patients with relapsing-remitting or progressive MS (RRMS or PMS) and HCs and between groups of patients with RRMS taking 6 commonly used disease-modifying drugs. RESULTS In untreated patients with MS, significantly higher frequencies of Th17 cells in the RRMS population compared with HC and lower frequencies of B-memory/B-regulatory cells as well as higher percentages of B-mature cells in patients with PMS compared with HCs emerged.