Using machine learning with passive wearable sensors to pilot the detection of eating disorder behaviors in everyday life.

BACKGROUND: Eating disorders (ED) are serious psychiatric disorders, taking a life every 52 minutes, with high relapse. There are currently no support or effective intervention therapeutics for individuals with an ED in their everyday life. The aim of this study is to build idiographic machine learning (ML) models to evaluate the performance of physiological recordings to detect individual ED behaviors in naturalistic settings. METHODS: From an ongoing study (Final N = 120), we piloted the ability for ML to detect an individual's ED behavioral episodes (e.g. purging) from physiological data in six individuals diagnosed with an ED, all of whom endorsed purging. Participants wore an ambulatory monitor for 30 days and tapped a button to denote ED behavioral episodes. We built idiographic (N = 1) logistic regression classifiers (LRC) ML trained models to identify onset of episodes (~600 windows) v. baseline (~571 windows) physiology (Heart Rate, Electrodermal Activity, and Temperature). RESULTS: Using physiological data, ML LRC accurately classified on average 91% of cases, with 92% specificity and 90% sensitivity. CONCLUSIONS: This evidence suggests the ability to build idiographic ML models that detect ED behaviors from physiological indices within everyday life with a high level of accuracy. The novel use of ML with wearable sensors to detect physiological patterns of ED behavior pre-onset can lead to just-in-time clinical interventions to disrupt problematic behaviors and promote ED recovery.

Influence of at-risk family interactions on the course of psychiatric care in adolescence.

Dysparenting, referring to inappropriate parental attitudes, is a vulnerability factor for mental disorders during adolescence and a therapeutic leverage, yet clinicians lack reliable tools to assess it in daily clinical practice. Moreover, the effect of this dysparenting on the amount of psychiatric care remains unclear. The Family and Care study aims to develop the at-risk family interactions and levers (ARFIL) scale, a comprehensive 30-item clinical scale, and to assess in a cross-sectional design, the impact of these at-risk family interactions on the care of adolescents (n = 425) hospitalized in psychiatry and aged 13-19 years old. Factorial analysis shows that the ARFIL scale consists of three main dimensions associated with cohesion/conflicts, love/hostility, and autonomy/control with good psychometric properties. Multivariate regressions show that the ARFIL intensity score predicts the duration of hospital care, regardless of age, gender, medical severity on admission, assessed by the Global Assessment of Functioning scale, the presence of maltreatment and psychiatric diagnoses. Moreover, the ARFIL diversity score (number of items present regardless of their severity) predicts both the number and duration of hospitalizations. At-risk family interactions are a determining dimension of psychiatric adolescent care, and the ARFIL scale could constitute a valuable tool, not only for holistic evaluation and treatment, but also for prevention.

Osteoblast-Derived Matrix Vesicles Exhibit Exosomal Traits and a Unique Subset of microRNA: Their Caveolae-Dependent Endocytosis Results in Reduced Osteogenic Differentiation.

Matrix vesicles (MVs) are nano-sized extracellular vesicles that are anchored in the extracellular matrix (ECM). In addition to playing a role in biomineralization, osteoblast-derived MVs were recently suggested to have regulatory duties. The aims of this study were to establish the characteristics of osteoblast-derived MVs in the context of extracellular vesicles like exosomes, assess their role in modulating osteoblast differentiation, and examine their mechanism of uptake. MVs were isolated from the ECM of MG63 human osteoblast-like cell cultures and characterized via enzyme activity, transmission electron microscopy, nanoparticle tracking analysis, Western blot, and small RNA sequencing. Osteoblasts were treated with MVs from two different culture conditions (growth media [GM]; osteogenic media [OM]) to evaluate their effects on the differentiation and production of inflammatory markers and on macrophage polarization. MV endocytosis was assessed using a lipophilic, fluorescent dye and confocal microscopy with the role of caveolae determined using methyl-ß-cyclodextrin. MVs exhibited a four-fold enrichment in alkaline phosphatase specific activity compared to plasma membranes; were 50-150 nm in diameter; possessed exosomal markers CD63, CD81, and CD9 and endosomal markers ALIX, TSG101, and HSP70; and were selectively enriched in microRNA linked to an anti-osteogenic effect and to M2 macrophage polarization. Treatment with GM or OM MVs decreased osteoblast differentiation. Osteoblasts endocytosed MVs using a mechanism that involves caveolae. These results support the hypothesis that osteoblasts produce MVs that participate in the regulation of osteogenesis.

[Prevention and treatment of antipsychotic induced weight gain]. / Preventie en behandeling van gewichts-toename bij antipsychotica.

BACKGROUND: Metformin is the most investigated pharmacological treatment of antipsychotics-induced weight gain (AIWG). Based on a systematic literature review, the first guideline for the treatment of AIWG with metformin was recently published. AIM: To present a step-by-step plan, based on recent literature and clinical experience to monitor, prevent, and treat AIWG. METHOD: Literature search to give specific advice on the choice of antipsychotic medication, stop, dose reduction or switch of antipsychotic, screening, non-pharmacological and pharmacological interventions to prevent and treat AIWG. RESULTS: Especially in the first year of antipsychotic treatment timely detection of AIWG through regular monitoring is pivotal. The best way to treat AIWG is to prevent its emergence by choosing an antipsychotic with a favourable metabolic profile. Secondly, by titration of antipsychotic medication to the lowest dose possible. Achieving a healthy lifestyle shows a limited beneficial effect on AIWG. Drug-induced weight loss can be attained by the addition of metformin, topiramate, or aripiprazole. Topiramate and aripiprazole can improve positive and negative residual symptoms of schizophrenia. The evidence on liraglutide is scarce. All augmentation strategies may cause side effects. Besides, in case of nonresponse augmentation therapy should be stopped to prevent unnecessary polypharmacy. CONCLUSION: In the revision of the Dutch multidisciplinary guideline for schizophrenia, the detection, prevention, and treatment of AIWG deserves more attention.

miR-122 and the WNT/ß-catenin pathway inhibit effects of both interleukin-1ß and tumor necrosis factor-α in articular chondrocytes in vitro.

Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and WNT/ß-catenin signaling cause dysregulation of rat primary articular chondrocytes (rArCs), resulting in cartilage extracellular matrix destruction and osteoarthritis (OA) progression. microRNA (miR) miR-122 represses these effects whereas miR-451 exacerbates IL-1ß-stimulated matrix metalloproteinase-13 (MMP-13) and prostaglandin E2 (PGE2) production. The goals of this study were to evaluate crosstalk between these signaling pathways and determine if miR-122 and miR-451 exert their protective/destructive effects through these pathways in an in vitro model of OA. Primary rArCs were treated with IL-1ß or TNF-α for 24 h and total DNA, MMP-13, and PGE2, as well as expression levels of miR-122 and miR-451 were measured. After 24-h transfection with miR-122, miR-451, miR-122-inhibitor, or miR-451-inhibitor, rArCs were treated with or without TNF-α for 24 h; total DNA, MMP-13, and PGE2 were measured. Similarly, cells were treated with WNT-agonist lithium chloride (LiCl), WNT-antagonist XAV-939 (XAV), or PKF-118-310 (PKF) with and without IL-1ß or TNF-α stimulation. Both IL-1ß and TNF-α-stimulation increased MMP-13 and PGE2 production. Transfection with miR-122 prevented TNF-α-stimulated increases in MMP-13 and PGE2 whereas transfection with miR-451 did not change these levels. No differences were found in MMP-13 or PGE2 production with miR-122 or miR-451 inhibitors. LiCl treatment decreased PGE2 production in cultures treated with TNF-α, but not MMP-13. XAV increased TNF-α-stimulated increases in PGE2 but not MMP-13. LiCl reduced IL-1ß-stimulated increases in MMP-13 and PGE2. XAV and PKF increased IL-1ß-stimulated increases in MMP-13 and PGE2. In this in vitro OA model, miR-122 protects against both IL-1ß and TNF-α stimulated increases in MMP-13 and PGE2 production. miR-451 does not act through the TNF-α pathway. The WNT/ß-catenin pathway regulates the effects of IL-1ß and TNF-α stimulation. This study suggests that miR-122 can be used as a treatment or prevention for OA.

Squamous papilloma of the proximal oesophagus associated with an inlet patch: a potential aetiological relationship.

Squamous papillomas are rare benign lesions that can be found in the oesophagus. It has been theorised that irritation of the esophageal mucosa leads to squamous papilloma formation. There is evidence to suggest that squamous papillomas of the distal oesophagus are related to irritation due to reflux of gastric acid. In this case report, we describe for the first time a squamous papilloma of the upper oesophagus located just distal to an inlet patch. Inlet patches consist of gastric mucosa located in the proximal oesophagus. They are capable of producing acid. This case raises the possibility that just as squamous papillomas of the distal oesophagus may be related to acid exposure from the reflux of gastric acid, squamous papillomas of the proximal oesophagus may be related to acid exposure from the locally-produced acid of inlet patches.

Clinical characteristics and outcomes of immunosuppressed patients hospitalized with COVID-19: experience from London.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health emergency. Despite the widely hypothesized role of a cytokine storm in disease severity, no study thus far has explored the association between immunosuppression and disease severity in patients hospitalized with COVID-19. OBJECTIVE: This study aimed to examine the association between the use of immunosuppressant medication and outcomes of patients hospitalized with COVID-19. METHODS: Nine hundred and eighty-one consecutive patients hospitalized between 12 March 2020 and 15 April 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were enrolled in this cohort study and subdivided by immunosuppression status. The patients were followed up for a minimum of 28 days (median 37 days) for the primary end-point of mortality. Secondary end-points included the composite of intubation or death, and the composite of mortality, intubation or continuous positive airway pressure (CPAP) requirement. RESULTS: During the follow-up period, 354 (36.1%) of study patients died. The immunosuppressed cohort (n = 31) had significantly higher mortality rates (aHR: 2.067, 95% CI: 1.20-3.57, P = 0.009). There was no association between immunosuppression and the composite end-point of mortality or intubation (aHR: 1.49 95% CI: 0.88-2.51, P = 0.14) and of the composite end-point of mortality, intubation or CPAP (aHR: 1.36 95% CI: 0.81-2.30 P = 0.245). CONCLUSION: In this cohort study of 981 confirmed COVID-19 patients consecutively hospitalized at a large North West London hospital, immunosuppressant use was associated with significantly higher mortality rates. These results support the current UK government's early isolation ('shielding') policy for these individuals and should be used to guide future research.

Regulation of inflammatory and catabolic responses to IL-1ß in rat articular chondrocytes by microRNAs miR-122 and miR-451.

OBJECTIVE: miR-122 stimulates proliferation of growth plate chondrocytes whereas miR-451 stimulates terminal differentiation and matrix turnover. Here, we examined the potential of these microRNA as regulators of articular chondrocytes using an in vitro model of osteoarthritis. METHODS: miR-122 and miR-451 presence in rat articular cartilage was assessed using the anterior cruciate ligament transection model of OA. In vitro testing used first passage rat articular chondrocytes (rArCs) that were transfected with lipofectamine (Lipo) and miR-122 or miR-451 for 24-h, then treated with 10 ng/mL IL-1ß in order to mimic an osteoarthritic environment. Conditioned media were collected and MMP13, PGE2 and OA-related cytokines were measured. Matrix vesicles were collected from cell layer lysates using ultra-centrifugation. Cells were treated with miR-122 or miR-451 inhibitors to verify miR-specific effects. RESULTS: Both miR-122 and miR-451 were increased in the OA articular cartilage compared to healthy tissue; rArCs expressed both microRNAs in MVs. miR-122 prevented IL-1ß-dependent increases in MMP-13 and PGE2, whereas miR-451 significantly increased the IL-1ß effect. Multiplex data indicated that miR-122 reduced the stimulatory effect of IL-1ß on IL-1α, IL-2, Il-4, IL-6, GM-CSF, MIP-1A, RANTES and VEGF. In contrast, IL-2, IL-4, IL-6, GM-CSF, and MIP-1A were increased by miR-451 while VEGF was decreased. Inhibiting miR-122 exacerbated the response to IL-1ß indicating endogenous levels of miR-122 were present. There were no differences in MMP-13 or PGE2 with miR-451 Locked Nucleic Acid (LNA) inhibitor treatment. CONCLUSIONS: Both miRs were elevated in OA in a rat bilateral anterior cruciate ligament transection (ACLT) model. miR-122 prevented, while miR-451 exacerbated the effects of IL-1ß on rArCs.

[COVID-19 and severe mental illness, especially in clozapine use]. / COVID-19 en ernstige psychiatrische aandoeningen, in het bijzonder bij clozapinegebruik.

BACKGROUND: The Clozapine Plus Working Group is frequently consulted for advice on measures in case of infection with SARSCoV-2 and on vaccination against COVID-19 in patients receiving clozapine.

AIM: Inform about risks of infection with SARS-CoV-2 in patients with severe mental illness (SMI), patients with schizophrenia spectrum disorders (SSD), and patients treated with clozapine. Advise on monitoring of clozapine plasma levels and white blood cell count and differential in COVID-19 and after vaccination, as well as measures to be taken.

METHOD: Literature research and case studies.

RESULTS: SMI patients and in particular SSD patients have an increased risk of infection with SARS-CoV-2 with more hospitalizations and higher mortality than non-psychiatric patients. Patients using clozapine may be at greater risk of infection. SARS-CoV-2 infection may cause a dangerous increase of clozapine plasma levels and generally mild and short-term granulocytopenia and lymphocytopenia, which are usually not a result of clozapine treatment.

CONCLUSION: In case of COVID-19 extra alertness is required in patients with SMI and especially SSD. In clozapine users, in case of COVID-19, reduction in dose by half to three quarters of the original dose is recommended. When patients develop granulocytopenia, SARS-CoV-2 should be considered as the cause and not immediately clozapine. SMI patients and clozapine users in particular belong to a high risk group with a medical indication for early vaccination.

[Validation of the Dutch Glasgow Anti- psychotic Side-Effect Scale for Clozapine]. / Glasgow Antipsychotica Bijwerkingen Schaal voor Clozapine; validatie van de Nederlandstalige versie.

BACKGROUND: To monitor the unique side effect pattern of clozapine, the Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C) was developed in English and validated. This questionnaire was previously translated to Dutch, and revised, but not yet validated. AIM: The current study concerns the validation of the second revision of the GASS-C-NL-R2 for the Dutch language. METHOD: Two Spearman correlation tests were conducted to compare GASS-C-NL-R2 with the Dutch version of the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) at two time p´oints. There was one week between these two time points. The test-retest reliability was determined using a Spearman correlation test and Cronbach's alpha on the GASS-C-NL-R2 between the two time points. In addition, a factor analysis was performed. RESULTS: Spearman's correlation coefficient between the GASS-C-NL-R2 and the LUNSERS was 0.830 (p < 0.001, n = 72) at the first time point and 0.684 (p < 0.001, n = 50) at the second time point. GASS-C-NL-R2 also had a strong test-retest reliability: Spearman's correlation coefficient was 0.680 (p < 0.001; n = 46), and Cronbach's alpha was 0.847, n = 78. Factor analysis showed that all questions were relevant. CONCLUSION: The current study shows that GASS-C-NL-R2 is a valid and reliable questionnaire to monitor side effects related to clozapine with a relatively high prevalence. Future studies should focus on the practical utility of GASS-C-NL-R2 with a larger sample size.

Association between liver fibrosis and cognition in a nationally representative sample of older adults.

BACKGROUND AND PURPOSE: Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults. METHODS: We examined the association between liver fibrosis and cognitive performance among participants aged 60 years and older in the US National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease. RESULTS: Among 3217 adult participants, the mean age was 69 years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% [95% confidence interval (CI) 4.0-6.0] had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (ß -0.39; 95% CI -0.58, -0.21), language fluency (ß -0.46; 95% CI -0.72, -0.21), and attention/concentration (ß -1.34; 95% CI -2.25, -0.43), but not delayed recall (ß -0.10; 95% CI -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease. CONCLUSION: Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.

Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study.

COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalised patients is critical as the pandemic progresses. This observational cohort study aimed to characterise the independent associations between the clinical outcomes of hospitalised patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, UK between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling. The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Scale <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality. These important data will aid clinical risk stratification and provide direction for further research.

Acellular mineralized allogenic block bone graft does not remodel during the 10 weeks following concurrent implant placement in a rabbit femoral model.

OBJECTIVES: Due to bone loss, endosseous implants often require addition of a bone graft to support adequate primary fixation, bone regeneration, and osseointegration. The aim of this study was to compare effectiveness of autogenic and allogenic bone grafts when used during simultaneous insertion of the implant. MATERIALS AND METHODS: 4-mm-diameter rabbit diaphyseal bone autografts or allografts (n = 16/group) with a 3.2-mm pre-drilled hole in the center were placed into a 4 mm defect in the proximal femur of 3.5 kg male New Zealand White rabbits. Machined 3.2 × 10 mm grit-blasted, acid-etched titanium-aluminum-vanadium (Ti6Al4V) implants were placed. Control implants were placed into progressively drilled 3.2-mm holes in the contralateral limbs. Post-insertion day 70, samples were analyzed by micro-CT and calcified histology, or by mechanical torque and push-out testing followed by decalcified histology. RESULTS: Both grafts were integrated with the native bone. Micro-CT showed less bone volume (BV) and bone volume/total volume (BV/TV) in the allograft group, but histology showed no differences in BV or BV/TV between groups. Allograft lacked living cells, whereas autograft was cellularized. No difference was found in maximum removal torque between groups. Compressive loading at the graft-to-bone interface was significantly lower in allograft compared with autograft groups. CONCLUSIONS: There was less bone in contact with the implant and significantly less maximum compressive load in the allograft group compared with autograft. The allograft remained acellular as demonstrated by empty lacunae. Taken together, block allograft implanted simultaneously with an implant produces a poorer quality bone compared with autograft.

Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations.

BACKGROUND: COPD exacerbations have negative impact on patients' survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival. METHODS: This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation. RESULTS: Included were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13-41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p <  0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6-3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08-3.1, p <  0.05). CONCLUSIONS: Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.

[Appreciating COVID-19 as a child and adolescent psychiatrist on the move]. / Appréhender le COVID-19 au fil de l'eau en tant que psychiatre d'enfant et d'adolescent.

COVID-19 is a multi-organ disease due to an infection with the SARS-CoV2 virus. It has become a pandemic in early 2020. The disease appears less devastating in children and adolescents. However, stress, quarantine and eventually mourning have major impacts on development. It is difficult to describe what this pandemic implies for a child psychiatrist, other than by giving a first-hand account. I propose to go through the main ethical questions that have arisen; to describe how my hospital team has reorganized itself to meet the new demands and questions, in particular by opening a unit dedicated to people with autism and challenging behaviors affected by COVID-19; and to address, in a context of national discussion, how the discipline has sought to understand the conditions of a certain well-being during quarantine. Finally, I will try to conclude with more speculative reflections on re-opening.

Higher ER load is not associated with better outcome in stage 1-3 breast cancer: a descriptive overview of quantitative HR analysis in operable breast cancer.

PURPOSE: In breast cancer, hormone receptor (HR) status is generally a qualitative measure; positive or negative. Quantitatively measured oestrogen and progesterone receptors (ER and PR) are frequently proposed prognostic and predictive markers, some guidelines even provide different treatment options for patients with strong versus weak expression. AIM: To evaluate quantitative HR load assessed by immunohistochemistry as a prognostic and predictive measure in stage 1-3 breast cancer. METHODS: We reviewed all the available literature on quantitatively measured HRs using immunohistochemistry. RESULTS: All included studies (n = 19) comprised a cohort of 30,754 patients. Only 2 out of 17 studies found a clear correlation between higher quantitative ER and better disease outcome. Only one trial examined quantitative ER both as prognostic and predictive marker and found no association between ER% and survival. Ten studies examined quantitative PR load, only two of those found a significant correlation between higher PR load and better disease outcome. Two trials examined quantitative PR both as prognostic and predictive marker, neither found any association between PR% and disease outcome. CONCLUSIONS: There is no clear evidence for using quantitatively assessed ER and PR as prognostic nor predictive marker in patients with stage 1-3 breast cancer. We recommend only using a qualitative HR status in future guidelines and treatment considerations.

Inter-observer variability of manual contour delineation of structures in CT.

PURPOSE: To quantify the inter-observer variability of manual delineation of lesions and organ contours in CT to establish a reference standard for volumetric measurements for clinical decision making and for the evaluation of automatic segmentation algorithms. MATERIALS AND METHODS: Eleven radiologists manually delineated 3193 contours of liver tumours (896), lung tumours (1085), kidney contours (434) and brain hematomas (497) on 490 slices of clinical CT scans. A comparative analysis of the delineations was then performed to quantify the inter-observer delineation variability with standard volume metrics and with new group-wise metrics for delineations produced by groups of observers. RESULTS: The mean volume overlap variability values and ranges (in %) between the delineations of two observers were: liver tumours 17.8 [-5.8,+7.2]%, lung tumours 20.8 [-8.8,+10.2]%, kidney contours 8.8 [-0.8,+1.2]% and brain hematomas 18 [-6.0,+6.0] %. For any two randomly selected observers, the mean delineation volume overlap variability was 5-57%. The mean variability captured by groups of two, three and five observers was 37%, 53% and 72%; eight observers accounted for 75-94% of the total variability. For all cases, 38.5% of the delineation non-agreement was due to parts of the delineation of a single observer disagreeing with the others. No statistical difference was found for the delineation variability between the observers based on their expertise. CONCLUSION: The variability in manual delineations for different structures and observers is large and spans a wide range across a variety of structures and pathologies. Two and even three observers may not be sufficient to establish the full range of inter-observer variability. KEY POINTS: • This study quantifies the inter-observer variability of manual delineation of lesions and organ contours in CT. • The variability of manual delineations between two observers can be significant. Two and even three observers capture only a fraction of the full range of inter-observer variability observed in common practice. • Inter-observer manual delineation variability is necessary to establish a reference standard for radiologist training and evaluation and for the evaluation of automatic segmentation algorithms.

Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem.

We examined the prevalence and correlates of Helicobacter pylori (H. pylori) infection according to cytotoxin-associated gene A (CagA) phenotype, a main virulence antigen, among the ethnically diverse population groups of Jerusalem. A cross-sectional study was undertaken in Arab (N = 959) and Jewish (N = 692) adults, randomly selected from Israel's national population registry in age-sex and population strata. Sera were tested for H. pylori immunoglobulin G (IgG) antibodies. Positive samples were tested for virulence IgG antibodies to recombinant CagA protein, by enzyme-linked immunosorbent assay. Multinomial regression models were fitted to examine associations of sociodemographic factors with H. pylori phenotypes. H. pylori IgG antibody sero-prevalence was 83.3% (95% confidence interval (CI) 80.0%-85.5%) and 61.4% (95% CI 57.7%-65.0%) among Arabs and Jews, respectively. Among H. pylori positives, the respective CagA IgG antibody sero-positivity was 42.3% (95% CI 38.9%-45.8%) and 32.5% (95% CI 28.2%-37.1%). Among Jews, being born in the Former Soviet Union, the Middle East and North Africa, vs. Israel and the Americas, was positively associated with CagA sero-positivity. In both populations, sibship size was positively associated with both CagA positive and negative phenotypes; and education was inversely associated. In conclusion, CagA positive and negative infection had similar correlates, suggesting shared sources of these two H. pylori phenotypes.

Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009-2017.

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.

Doctors' decisions when disclosing their mental ill-health.

BACKGROUND: Understanding of what prevents doctors from seeking help for mental ill-health has improved. However, less is known about what promotes timely disclosure and the nature of doctors' decision making. AIMS: This study aimed to define how doctors make decisions about their own mental ill-health, and what facilitates disclosure. It explored the disclosure experiences of doctors and medical students; their attitudes to their decisions, and how they evaluate potential outcomes. METHODS: Qualitative, semi-structured interviews with UK doctors and medical students with personal experience of mental ill-health. Participants were recruited through relevant organizations, utilizing regular communications such as newsletters, e-mails and social media. Data were subject to a thematic analysis. RESULTS: Forty-six interviews were conducted. All participants had disclosed their mental ill-health to someone; not all to their workplace. Decision making was complex, with many participants facing multiple decisions throughout their careers. Disclosures were made despite the many obstacles identified in the literature; participants described enablers to and benefits of disclosing. The importance of appropriate responses to first disclosures was highlighted. CONCLUSIONS: Motivations to disclose mental ill-health are complex and multifactorial. An obstacle for one was an enabler for another. Understanding this and the importance of the first disclosure has important implications for how best to support doctors and medical students in need.