New directional archeomagnetic data of burned cave sediments from Switzerland and geomagnetic field variations in Central Europe

This paper presents new directional archeomagnetic data from nine Meso-/Neolithic fireplaces, sampled in a cave shelter, at Arconciel, in western Switzerland. Rock magnetic measurements indicate a homogenous magnetic mineralogy in all fireplaces, with magnetite as the main magnetic carrier. The remanent magnetization is stable and generally shows one characteristic directional component. Nine new directions, which were obtained from Arconciel, are combined with 356 other archeomagnetic data from a circular area with a radius of 700km around this site, to obtain a penalized least square spline fit for the past 9000yr. We found in general good agreement with other local compilations, such as the Balkan curve, the regional SCHA.DIF.8k model and with lake sediments from UK, Fennoscandia and Switzerland. Nevertheless, a time lag of several centuries is observed for a declination maximum between the archeomagnetic spline fit and the other European data records around 5900BC. This time lag is also observed in the Swiss lake sediment record; therefore we interpret this shift as a local feature of the Earth's magnetic fiel

Systematic review: Investigating the prognostic performance of four non‐invasive tests in alcohol‐related liver disease

BACKGROUND/AIMS: Mortality of Alcohol-related-Liver-Disease (ArLD) is increasing, and liver fibrosis stage is the best mortality predictor. Non-invasive-tests (NIT) are increasingly used to detect fibrosis, but their value as prognostic tests in chronic liver disease (CLD), and in particular in ArLD is less well recognized. We aimed to describe the prognostic performance of four widely used NITs (FIB4, ELF test, FibroScan and FibroTest) in ArLD. METHODS: Applying systematic-review methodology, four databases were searched from inception to May 2020. Inclusion/exclusion criteria were applied to search using MeSH terms and keywords. First and second reviewers independently screened results, extracted data and performed risk-of-bias assessment using Quality-In-Prognostic-Studies (QUIPS) tool. RESULTS: Searches produced 25,088 articles. After initial screening, 1,020 articles were reviewed independently by both reviewers. Eleven articles remained after screening for eligibility: one on ELF, four on FibroScan, four on FIB4, one on FIB4+FibroScan and one on FibroTest+FIB4. Area-Under-Receiving-Operator-Characteristics-curves (AUROCS) for outcome-prediction ranged from: 0.65-0.76 for FibroScan, 0.64-0.83 for FIB4, 0.69-0.79 for FibroTest and 0.72-0.85 for ELF. Studies scored low-moderate risk of bias for most domains, but high-risk in confounding/statistical reporting domains. The results were heterogeneous for outcomes and reporting, making pooling of data unfeasible. CONCLUSIONS: This systematic-review returned eleven papers, six of which were conference-abstracts and one unpublished manuscript. Whilst the heterogeneity of studies precluded direct comparisons of NITs, each NIT performed well in individual studies in predicting prognosis in ArLD (AUROCs >0.7 in each NIT category), and may add value to prognostication in clinical practice

Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse specialists using the ELF test

BBackground and aims: Alcohol use disorders (AUD) cause 7.2% of UK hospital admissions/year. Most are not managed by hepatologists and liver disease may be missed. We used the Enhanced Liver Fibrosis (ELF) test to investigate prevalence and associations of occult advanced liver fibrosis in AUD patients not known to have liver fibrosis. / Methods: Liver fibrosis was assessed using ELF in prospective patients referred to the Royal Free Hospital Alcohol Specialist Nurse (November 2018–December 2019). Known cases of liver disease were excluded. Patient demographics, blood tests, imaging data and alcohol histories recorded. Advanced fibrosis was categorised as ELF ≥ 10.5. / Results: The study included 99 patients (69% male, mean age 53.1 ± 14.4) with median alcohol intake 140 units/week (IQR 80.9–280), and a mean duration of harmful drinking of 15 years (IQR 10–27.5). The commonest reason for admission was symptomatic alcohol withdrawal (36%). The median ELF score was 9.62, range 6.87–13.78. An ELF score ≥ 10.5 was recorded in 28/99 (29%) patients, of whom 28.6% had normal liver tests. Within previous 5-years, 76% had attended A&E without assessment of liver disease. The ELF score was not associated with recent alcohol intake (p = 0.081), or inflammation (p = 0.574). / Conclusion: Over a quarter of patients with AUD had previously undetected advanced liver fibrosis assessed by ELF testing. ELF was not associated with liver inflammation or recent alcohol intake. The majority had recent missed opportunities for investigating liver disease. We recommend clinicians use non-invasive tests to assess liver fibrosis in patients admitted to hospital with AUD

The role of preoperative diffusion tensor imaging in predicting and improving functional outcome in pediatric patients undergoing epilepsy surgery: a systematic review

Objective: Diffusion tensor imaging (DTI) is a useful neuroimaging technique for surgical planning in adult patients. However, no systematic review has been conducted to determine its utility for pre-operative analysis and planning of Pediatric Epilepsy surgery. We sought to determine the benefit of pre-operative DTI in predicting and improving neurological functional outcome after epilepsy surgery in children with intractable epilepsy. Methods: A systematic review of articles in English using PubMed, EMBASE and Scopus databases, from inception to January 10, 2020 was conducted. All studies that used DTI as either predictor or direct influencer of functional neurological outcome (motor, sensory, language and/or visual) in pediatric epilepsy surgical candidates were included. Data extraction was performed by two blinded reviewers. Risk of bias of each study was determined using the QUADAS 2 Scoring System. Results: 13 studies were included (6 case reports/series, 5 retrospective cohorts, and 2 prospective cohorts) with a total of 229 patients. Seven studies reported motor outcome; three reported motor outcome prediction with a sensitivity and specificity ranging from 80 to 85.7 and 69.6 to 100%, respectively; four studies reported visual outcome. In general, the use of DTI was associated with a high degree of favorable neurological outcomes after epilepsy surgery. Conclusion: Multiple studies show that DTI helps to create a tailored plan that results in improved functional outcome. However, more studies are required in order to fully assess its utility in pediatric patients. This is a desirable field of study because DTI offers a non-invasive technique more suitable for children. Advances in knowledge: This systematic review analyses, exclusively, studies of pediatric patients with drug-resistant epilepsy and provides an update of the evidence regarding the role of DTI, as part of the pre-operative armamentarium, in improving post-surgical neurological sequels and its potential for outcome prediction

Is there scope to improve the selection of patients with alcohol-related liver disease for referral to secondary care? A retrospective analysis of primary care referrals to a UK liver centre, incorporating simple blood tests

OBJECTIVES: Twenty per cent of people with alcohol use disorders develop advanced fibrosis and warrant referral to secondary care. Improving outcomes in alcohol-related liver disease (ArLD) relies on its earlier detection in primary care with non-invasive tests (NIT). We aimed to determine the proportion of alcohol-related referrals who were diagnosed with advanced fibrosis in secondary care, the prevalence of both alcohol and fatty liver disease ('BAFLD') and the potential impact of NIT on referral stratification. DESIGN/SETTING: Retrospective analysis of all general practitioner-referrals with suspected ArLD/non-alcoholic fatty liver disease (NAFLD) to a UK hepatology-centre between January 2015 and January 2018. PARTICIPANTS: Of 2944 new referrals, 762 (mean age 55.5±13.53 years) met inclusion criteria: 531 NAFLD and 231 ArLD, of which 147 (64%) could be reclassified as 'BAFLD'. PRIMARY OUTCOME MEASURE: Proportion of referrals with suspected ArLD/NAFLD with advanced fibrosis as assessed by tertiary centre hepatologists using combinations of FibroScan, imaging, examination and blood tests and liver histology, where indicated. SECONDARY OUTCOME MEASURES: Included impact of body mass index/alcohol consumption on the odds of a diagnosis of advanced fibrosis, and performance of NIT in predicting advanced fibrosis in planned post-hoc analysis of referrals. RESULTS: Among ArLD referrals 147/229 (64.2%) had no evidence of advanced fibrosis and were judged 'unnecessary'. Advanced fibrosis was observed in men drinking ≥50 units per week (U/w) (OR 2.74, 95% CI 1.51 to 5, p=0.001) and ≥35 U/w in women (OR 5.11, 95% CI 1.31 to 20.03, p=0.019). Drinking >14 U/w doubled the likelihood of advanced fibrosis in overweight/obesity (OR 2.11; 95% CI 1.44 to 3.09; p<0.001). Use of fibrosis 4 score could halve unnecessary referrals (OR 0.50; 95% CI 0.32 to 0.79, p=0.003) with false-negative rate of 22%, but was rarely used. CONCLUSIONS: The majority of referrals with suspected ArLD were deemed unnecessary. NIT could improve identification of liver damage in ArLD, BAFLD and NAFLD in primary care. Anecdotal thresholds for harmful drinking (35 U/w in women and 50 U/w in men) were validated. The impact of alcohol on NAFLD highlights the importance of multi-causality in chronic liver disease

PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic (PRECODE): protocol of a rapid mixed-methods study in the UK

BACKGROUND: The implementation of lockdowns in the UK during the COVID-19 pandemic resulted in a system switch to remote primary care consulting at the same time as the incidence of domestic violence and abuse (DVA) increased. Lockdown-specific barriers to disclosure of DVA reduced the opportunity for DVA detection and referral. The PRECODE (PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic) study will comprise quantitative analysis of the impact of the pandemic on referrals from IRIS (Identification and Referral to Improve Safety) trained general practices to DVA agencies in the UK and qualitative analysis of the experiences of clinicians responding to patients affected by DVA and adaptations they have made transitioning to remote DVA training and patient support. METHODS/DESIGN: Using a rapid mixed method design, PRECODE will explore and explain the dynamics of DVA referrals and support before and during the pandemic on a national scale using qualitative data and over four years of referrals time series data. We will undertake interrupted-time series and non-linear regression analysis, including sensitivity analyses, on time series of referrals to DVA services from routinely collected data to evaluate the impact of the pandemic and associated lockdowns on referrals to the IRIS Programme, and analyse key determinants associated with changes in referrals. We will also conduct an interview- and observation-based qualitative study to understand the variation, relevance and feasibility of primary care responses to DVA before and during the pandemic and its aftermath. The triangulation of quantitative and qualitative findings using rapid analysis and synthesis will enable the articulation of multiscale trends in primary care responses to DVA and complex mechanisms by which these responses have changed during the pandemic. DISCUSSION: Our findings will inform the implementation of remote primary care and DVA service responses as services re-configure. Understanding the adaptation of clinical and service responses to DVA during the pandemic is crucial for the development of evidence-based, effective remote support and referral beyond the pandemic. TRIAL REGISTRATION: PRECODE is an observational epidemiologic study, not an intervention evaluation or trial. We will not be reporting results of an intervention on human participants

Immunoblastic morphology as a possible prognostic indicator for the outcome of the patients with diffuse large B cell lymphoma in era of the rituximab based treatment: single centre experience

Recently the results from one large prospective study indicated that immunoblastic morphology and not immunohistohemical features predict the outcome of the Diffuse large B lymphoma (DLBL). In order to investigate the prediction value of the immunoblastic morphology (IB) as a possible prognostic indicator for the outcome of our DLBL patient treated with the Rituximab (R)-CHOP regimen we conducted a retrospective study. Our study enrolled 192 DLBL patients diagnosed and treated at the University Clinic of Hematology in the period between February 2002 and December 2007. They were all treated with R-CHOP regimen and the median follow-up of the patient was 36 months. We analyzed the biopsy samples immunohistochemically for markers of germinal center (BCL6), post-germinal center (MUM1) and apoptosis (BCL2).The patients were categorized as DLBL(132; 68.7%), IB(60; 31.2). The median overall survival time (OS) were 59.3 months in DLBL group and 42.2 months in IB group, and time to treatment (TT) were 56.8 and 30.6 months respectively for the IB group. The DLBL and IB groups were comparable regarding the age, gender distributions and all others already established prognostic parameters as performance status, advanced IPI, albumin level except for the low IPI 0-2 which was statistically associated with the DLBL group (p=.024). Our results did not show any statistical survival advantage and better outcome for the patient classified as DLBL when treated with R-CHOP and indicate that immunohistohemical markers do not really reflect the molecular diversity of the tumor.  Our work shows that IB morphology is a major risk factor in DLBL patients treated with R-CHOP. Therefore this morphology appears to capture some adverse molecular events that a currently hard to detect with routine diagnostic procedures.

The changing health impact of vaccines in the COVID-19 pandemic: a modeling study

Much of the world’s population had already been infected with COVID-19 by the time the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or has happened since, and it left a global imprinting of immunity that changed the COVID-19 landscape. In this study, we simulate a South African population and demonstrate how population-level vaccine effectiveness and efficiency changed over the course of the first 2 years of the pandemic. We then introduce three hypothetical variants and evaluate the impact of vaccines with different properties. We find that variant-chasing vaccines have a narrow window of dominating pre-existing vaccines but that a variant-chasing vaccine strategy may have global utility, depending on the rate of spread from setting to setting. Next-generation vaccines might be able to overcome uncertainty in pace and degree of viral evolution