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BackgroundPublic Health England recently called for the establishment of services to help people to safely stop prescribed drugs associated with dependence and withdrawal, including benzodiazepines, z-drugs, antidepressants, gabapentinoids and opioids. NICE identified a lack of knowledge about the best model for such service delivery. Therefore, we performed a global survey of existing deprescribing services to identify common practices and inform service development.MethodsWe identified existing deprescribing services and interviewed key personnel in these services using an interview co-produced with researchers with lived experience of withdrawal. We summarised the common practices of the services and analysed the interviews using a rapid form of qualitative framework analysis.ResultsThirteen deprescribing services were included (8 UK, 5 from other countries). The common practices in the services were: gradual tapering of medications often over more than a year, and reductions made in a broadly hyperbolic manner (smaller reductions as total dose became lower). Reductions were individualised so that withdrawal symptoms remained tolerable, with the patient leading this decision-making in most services. Support and reassurance were provided throughout the process, sometimes by means of telephone support lines. Psychosocial support for the management of underlying conditions (e.g. CBT, counselling) were provided by the service or through referral. Lived experience was often embedded in services through founders, hiring criteria, peer support and sources of information to guide tapering.ConclusionWe found many common practices across existing deprescribing services around the world. We suggest that these ingredients are included in commissioning guidance of future services and suggest directions for further research to clarify best practice.

Background: Stopping antidepressants commonly causes withdrawal symptoms, which can be severe and long-lasting. National Institute for Health and Care Excellence (NICE) guidance has been recently updated to reflect this; however, for many years withdrawal (discontinuation) symptoms were characterised as ‘usually mild and self-limiting over a week’. Consequently, withdrawal symptoms might have been misdiagnosed as relapse of an underlying condition, or new onset of another medical illness, but this has never been studied. Method: This paper outlines the themes emerging from 158 respondents to an open invitation to describe the experience of prescribed psychotropic medication withdrawal for petitions sent to British parliaments. The accounts include polypharmacy (mostly antidepressants and benzodiazepines) but we focus on antidepressants because of the relative lack of awareness about their withdrawal effects compared with benzodiazepines. Mixed method analysis was used, including a ‘lean thinking’ approach to evaluate common failure points. Results: The themes identified include: a lack of information given to patients about the risk of antidepressant withdrawal; doctors failing to recognise the symptoms of withdrawal; doctors being poorly informed about the best method of tapering prescribed medications; patients being diagnosed with relapse of the underlying condition or medical illnesses other than withdrawal; patients seeking advice outside of mainstream healthcare, including from online forums; and significant effects on functioning for those experiencing withdrawal. Discussion: Several points for improvement emerge: the need for updating of guidelines to help prescribers recognise antidepressant withdrawal symptoms and to improve informed consent processes; greater availability of non-pharmacological options for managing distress; greater availability of best practice for tapering medications such as antidepressants; and the vital importance of patient feedback. Although the patients captured in this analysis might represent medication withdrawal experiences that are more severe than average, they highlight the current inadequacy of health care systems to recognise and manage prescribed drug withdrawal, and patient feedback in general.

Abstract Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1+ sEV to modulate T cells needs to be clarified. Herein we analyzed sEV produced by human DLBCL cell lines and EBV-transformed B cell-lymphoblastoid cell lines (LCLs), a model allowing autologous T cell co-cultures. We determined CD20 and PD-L1 levels on plasma sEV from patient samples vs healthy volunteers (HV). sEV functional relevance was also investigated on CD4+ and CD8+ T cells. sEV derived from all cell lines showed an enrichment of CD20 and a high glycosylated PD-L1 expression when compared to cell lysates. High PD-L1 expression on LCL-derived sEV was associated with higher CD4+ and CD8+ T cell apoptosis. In patients, plasma sEV concentration was higher vs HV. Compared to sEV-CD20 level that seemed higher in patients, PD-L1 level in sEV was not different from those of HV. A high glycosylated PD-L1 level was shown in sEV from both patients and HV plasma samples, that was associated with the same inhibiting effect on activated T cells. We conclude that sEV derived from EBV-transformed B cells realize an immunosuppressive role that involved cell–cell interaction and probably at least PD-L1. Furthermore, our findings suggest the potential of circulating sEV as a source of biomarkers in DLBCL, notably to have information on immunotherapeutic target levels of parental tumor cells.

Abstract Early and sensitive biomarkers of liver dysfunction and drug-induced liver injury (DILI) are still needed, both for patient care and drug development. We developed the Serum Enhanced Binding (SEB) test to reveal post-transcriptional modifications (PTMs) of human serum albumin resulting from hepatocyte dysfunctions and further evaluated its performance in an animal model. The SEB test consists in spiking serum ex-vivo with ligands having specific binding sites related to the most relevant albumin PTMs and measuring their unbound fraction. To explore the hypothesis that albumin PTMs occur early during liver injury and can also be detected by the SEB test, we induced hepatotoxicity in male albino Wistar rats by administering high daily doses of ethanol and CCl4 over several days. Blood was collected for characterization and quantification of albumin isoforms by high-resolution mass spectrometry, for classical biochemical analyses as well as to apply the SEB test. In the exposed rats, the appearance of albumin isoforms paralleled the positivity of the SEB test ligands and histological injuries. These were observed as early as D3 in the Ethanol and CCl4 groups, whereas the classical liver tests (ALT, AST, PAL) significantly increased only at D7. The behavior of several ligands was supported by structural and molecular simulation analysis. The SEB test and albumin isoforms revealed hepatocyte damage early, before the current biochemical biomarkers. The SEB test should be easier to implement in the clinics than albumin isoform profiling.

People’s perception of forensic evidence is greatly influenced by crime TV series. The analysis of the human voice is no exception. However, unlike fingerprints—with which fiction and popular beliefs draw an incorrect parallel—the human voice varies according to many factors, can be altered deliberately, and its potential uniqueness has yet to be proven. Starting with a cursory examination of landmarks in forensic voice analysis that exemplify how the voiceprint fallacy came about and why people think they can recognize people’s voices, we then provide a thorough inspection of over 100 excerpts from TV series. Through this analysis, we seek to characterize the narrative and aesthetic processes that fashion our perception of scientific evidence when it comes to identifying somebody based on voice analysis. These processes converge to exaggerate the reliability of forensic voice analysis. We complement our examination with plausibility ratings of a subset of excerpts. We claim that these biased representations have led to a situation where, even today, one of the main challenges faced by forensic voice specialists is to convince trial jurors, judges, lawyers, and police officers that forensic voice comparison can by no means give the sort of straightforward answers that fingerprints or DNA permit.

Acquiring a consistent accent and targeting a native standard like Received Pronunciation (RP) or General American (GA) are prerequisites for French learners who plan to become English teachers in France. Reliable methods to assess learners’ productions are therefore extremely valuable. We recorded a little over 300 students from our English Studies department and performed auditory analysis to investigate their accents and determine how close to native models their productions were. Inter-rater comparisons were carried out; they revealed overall good agreement scores which, however, varied across phonetic cues. Then, automatic speech recognition (ASR) and automatic accent identification (AID) were applied to the data. We provide exploratory interpretations of the ASR outputs, and show to what extent they agree with and complement our auditory ratings. AID turns out to be very consistent with our perception, and both types of measurements show that two thirds of our students favour an American, and the remaining third, a British pronunciation, although most of them have mixed features from the two accents.

BackgroundIn the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.MethodsA FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.ResultsSamples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].ConclusionsThis study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

Abstract We report the case of a 36‐year‐old patient who was initially managed for gynecomastia. The first biological analyses showed a moderately elevated alpha‐fetoprotein (AFP) level. After an endocrine etiology was excluded, an abdominal computed tomography scan showed typical focal nodular hyperplasia (FNH) proven by biopsy and showing expression of AFP in FNH cells. After follow‐up for 24 months, the serum AFP and liver radiology remained unchanged. The association between an elevated AFP and FNH is rarely described in the medical literature.

Background and study aims ESD in the colon is more challenging technically than in other locations. Here, we report the first comparative case series of colon ESD using a systematic countertraction strategy using two clips and a rubber band. Patients and methods Retrospective comparative study of classic versus countertraction colon ESD performed in colon ESD cases collected prospectively at Lyon Edouard Herriot Hospital and Limoges University Hospital from January 2016 until December 2017. Results The study included 192 cases (control = 76, countertraction = 116). Countertraction using the double clip and rubber band technique versus the control group resulted in a significant decrease in the procedure time (94.7 vs. 117 min; P = 0.004) and significant increases in procedure speed (28.2 vs. 16.7 mm2/min; P

The implementation of Peer Assisted Learning (PAL) on healthcare courses in Higher Education has been explored in a number of studies. This paper presents peer research conducted by final year undergraduate Speech & Language Therapy students into the experience of PAL mentees and mentors on the same course. The focus was on the effects of PAL on academic and professional development. Data were generated from standard PAL evluations and focus groups. Findings indicate that mentees benefit from PAL in terms of their university experience and learning. Engagement with PAL results from its structured yet informal nature and the enthusiasm of the mentors. The collaborative nature of PAL took time to develop, impacting on the behaviours of the mentees and mentors. All participants commented on gaining from PAL. Overall PAL offers mentees and mentors opportunities which enhance their academic learning and professional development.