"Time Consuming -but Time Well Spent": Hepatologists' Experiences with Delivering Palliative Care to Patients with End-Stage Liver Disease and Their Caregivers

Background: Palliative care (PC) is an integral part of managing patients with chronic illness and high symptom burden including end-stage liver disease (ESLD). Given the deficit in PC workforce, we trained Hepatologists with primary PC skills as a part of a comparative effectiveness trial (NCT03540771). This study explored the experiences of hepatologists trained to provide PC to patients with ESLD and their caregivers. Method(s): We conducted a qualitative interview study within the context of Pal-Liver, a PCORI-funded, 18-institution cluster-randomized comparative effectiveness trial of PC delivered by hepatologists (10 sites) vs PC specialist (8 sites) to ESLD patients and caregivers. Hepatologists completed a 12-week training course to develop skills in delivering primary PC for ESLD patients. Trained interviewers used a semi-structured guide to interview hepatologists (n=15) and PC specialists (n=15) to explore overall experiences in providing ESLD care, pre-and post-study challenges and benefits, and for hepatologists, experiences with training and providing primary palliative care. Phone interviews were digitally-recorded, transcribed verbatim, coded, and analyzed aided by NVIVO 12 software. Using a consensus-driven code book manifest and latent themes emerged. Here we report preliminary analysis of hepatologists' perspectives. Result(s): Hepatologists (n=15) 70% female;77% white, mean age 48 years from 8 hepatologist-provided palliative care institutions reported themes of: 1) primary PC training beneficial;2) time consuming but "time well spent" with additional primary PC integrated within routine ESLD care;3) ESLD care boundaries vs overlap: Who does what & when?;4) Covid-19 impact: challenges and opportunities;5) increased focus on caregivers' needs;6) patient reported outcome (PROs) measures improved communication about prognosis and tailoring PC interventions for physical and emotional symptoms, and 7) need for more case discussions and practical strategies. Conclusion(s): Training on primary PC skills assisted hepatologists to provide additional support to patients and increased their realization of caregivers' needs. Boundaries between primary and specialist PC for patients with ESLD are not well demarcated. Hepatologists found PROs useful in tailoring PC interventions. Future analysis will include comparisons between hepatology and specialist delivered PC to inform a pragmatic approach. (Figure Presented).

Could lockdown increase the incidence of eating disorders?

Introduction Spanish Governmen declared state of emergency in March 2020 to prevent coronavirus COVID-19 from spreading. During September and October 2020, at Child and Adolescent Psychiatry Unit we have attended patients who presented altered eating behaviors whose onset was during lockdown. We report a series of seven cases of adolescent girls between the ages of 11 and 16, who had no previous history of mental illness. During lockdown, they have presented restriction of food and increased physical exercise, with weight loss. Some of these patients have also presented food binges and purging behaviors. Objectives Review the impact of lockdown on eating behavior, specially on weight loss. Methods Literature review of scientific papers searching in Pubmed. Results There are articles that study the variations in eating habits and exercise ocurred during confinement. Most focus on two trends: on the one hand, increased intake and the tendency to a more sedentary life;on the other hand, the worsening of people with a previous diagnosis of eating disorder. However, there is a third trend for which there are few studies: the new appearance of restrictive eating behaviors, together with increased physical exercise, bingeing and purging. This is the case of the patients we present. These studies describe as a possible cause of these alterations that confinement is a novel situation, which generates stress, social isolation, boredom, anxiety and a feeling of loneliness, which can influence self-concept and eating behaviors. Conclusions Lockdown has favored a change in eating habits and exercise. More studies are needed on new-onset eating disorders.

LIVER INJURY ASSOCIATED WITH TURMERIC&≤x2013;A GROWING PROBLEM: NINE CASES FROM THE DRUG-INDUCED LIVER INJURY NETWORK [DILIN]

BACKGROUND: Turmeric (curcumin) is a commonly used over-the-counter herbal product whose uses include diarrhea, arthritis, cancer and even COVID-19. Recently turmeric has been implicated in cases of clinically apparent liver injury with jaundice. The aim of this case series is to describe the clinical, histologic and human leukocyte antigen (HLA) associations of turmeric-associated hepatotoxicity as seen in the U.S. Drug Induced Liver Injury Network (DILIN) Prospective Study. METHODS: All adjudicated cases enrolled in DILIN between 2003-2020 with turmeric as an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were collected and analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. RESULTS: Of 1697 cases of drug-induced liver injury judged to be definite, highly likely or probable (high confidence), nine (0.5%) were attributed to turmeric, all of which were enrolled since 2012, and 6 since 2017 (Figure). The 9 cases included 7 women, 8 whites, with a mean age of 51 years (range, 35-62 years) and BMI 25 kg/m2 (range, 15-40). Seven patients used alcohol, but none to excess, and none had underlying liver disease. Turmeric was used for an average of 102 days before onset of injury (range, 30-425 days). Initial mean ALT was 1179 U/L (range, 328-2245), ALP 211 U/L (41-441), total bilirubin 5.9 mg/dL (1.2-10.8), and INR 1.0 (0.9-1.2). Six patients developed jaundice, and serum bilirubin peaked at 9.6 mg/dL (0.8-26), and INR 2.3 (1.0- 9.7). Liver injury was hepatocellular in 8 patients (mean R = 22). Five patients had elevated antinuclear antibody (ANA) titer and two anti-smooth muscle (ASM) antibody, but none were treated with corticosteroids. Liver biopsy in 5 patients showed portal and lobular mixed inflammatory infiltrates with lymphocytes and eosinophils typical of drug-induced liver injury. Five patients were hospitalized, and one patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products analyzed;3 also contained piperine (black pepper), and none contained green tea. Of 7 patients with HLA typing available, 4 carried HLA-B*35:01, a class I HLA allele previously implicated in both green tea and Polygonum multiflorum hepatotoxicity. CONCLUSION: Liver injury due to turmeric appears to be increasing, perhaps, reflecting usage patterns or increased combination with black pepper, which increases its absorption. Turmeric liver injury, similar to that caused by other polyphenolic herbal products, is typically hepatocellular, with a latency of 1 to 6 months, and is linked to HLA-B*35:01. While most cases are self-limited, the injury can be severe and result in death or liver transplantation.

Nurses' perception regarding their health and working conditions during the COVID-19 pandemic

Objective: to identify working conditions and their effects on nursing professionals' health during the COVID-19 pandemic, based on the workers' own perceptions.

Technology implemented to job performance in COVID-19 times in uncontrolled scenarios

The main purpose of this article is to analyze job performance in the times of COVID 19 in uncontrolled scenarios in Lima in the year 2021. The research presents a basic type, a qualitative approach, and the inquiry process is inductive. The method is phenomenological, since it seeks to describe and understand the research variable: job performance under the COVID 19 scenario, based on the experiences and experiences of the participants. It was applied to 5 employees (1 Director, 1 Coordinator and 03 Assistants) belonging to an organization based in Lima. The semi-structured interview technique was obtained, which focuses on the dialogue between two people and lasts between 25 and 35 minutes, through telephone calls and video calls. © 2022, Associacao Iberica de Sistemas e Tecnologias de Informacao. All rights reserved.

Standard Radiotherapy Fractionation Toxicity Versus Ultra-Hypofractionation In Breast Cancer

Purpose or Objective Radiotherapy is an essential treatment in the local control of breast cancer. Standard treatment is currently carried out in 15 daily sessions. At present, following the results of the phase III Fast-Foward trial and in view of the situation triggered by COVID-19, the number of sessions has been reduced to 5. The RHEMA (extreme hypofractionated radiotherapy in breast cancer) study has been initiated in Spain. It is a multi-hospital study designed to determine the evolution of the change in fractionation. The hypothesis is that the change in fractionation does not increase acute toxicity. The aim of the study was to determine whether there are differences in acute skin toxicity in breast cancer patients who receive adjuvant radiotherapy according to the different fractionation schedules applied. Materials and Methods We retrospectively analysed skin toxicity in patients treated with glandular radiotherapy at the end of treatment and one month later. Out of 75 patients treated with the ultra-hypofractionated schedule, 58 patients with a follow-up of more than 1 month were compared with 38 patients who received the standard schedule, all of whom were treated in 2020 in the Multihospital Clinical Unit of Radiation Oncology of Aragon. In the case of the ultra-hypofractionated treatment, as indicated in the GEORM (Spanish group of breast radiation oncology) guidelines at the beginning of the pandemic, was carried out in 5 sessions with a total dose of 26 Gy over the breast and 29 Gy over the tumour bed, while the standard treatment, consisted in 15 sessions with a total dose of 40.5 Gy over the breast and 48 Gy over the tumour bed. Results The median age was 61 years in the standard group and 63.4 years in the ultra-hypofractionated group. No significant differences were observed in the histological profile. Differences were found in toxicity at the end of treatment, being significantly higher in the standard group (p 0.03). On the other hand, no differences were found in toxicity one month after the end of treatment. Grade 2 toxicity appeared in 2 patients from the ultra-hypofractionated group and 4 from the standard group, with no significant difference (p 0.943). There were no differences in the development of grade 1 toxicity and no grade 3 or higher toxicity was observed. Conclusion It can be concluded that the use of the ultra-hypofractionation schedule compared to standard treatment was not associated with an increase in acute skin toxicity in our series. This is a change in fractionation that could be adopted as a routine treatment in radiation oncology departments after verifying the results with a larger number of patients and a longer follow-up.

The shock of lockdown on the spending on wine in the Iberian market: the effects of procurement and consumption patterns

Purpose: This study aims to provide a better understanding of the behaviour of wine consumers in a completely new and unexpected setting, that is, a forced lockdown due to the COVID-19 pandemic. It seeks to explain consumer decisions and the probability of changes occurring in wine expenditure compared to a normal situation. Design/methodology/approach: The empirical analysis, conducted on a representative sample of Iberian consumers and based on the random utility theory, consists in the application of a multinomial logit model, setting the “usual” pattern of expenditure as a baseline category. Findings: The results show that the coronavirus pandemic could have changed alcohol drinking habits. Consumers generally spent less on wine during the lockdown, maybe due to the uncertainty regarding their future income and professional situation. Those people more likely to spend more on wine were those who increased their wine consumption during the lockdown, those who drank for romantic purposes, those who purchased less wine in supermarkets but more online, those who used a wine app and those living in urban areas. The increased consumption of other alcoholic beverages also increases the probability of spending less than usual on wine. Additionally, the absence of certain reasons for drinking wine other than social purposes, such as wine and food pairing, its taste and relaxing effects, together with the previous consumption pattern leads to a decrease in the probability of spending less per bottle. Originality/value: This paper makes a significant contribution to the understanding of the determinants of wine consumption in a very abnormal setting, an imposed lockdown and provides important policy implications. The findings show that managers and policymakers should pay attention to the different influence of variables related to behaviour and consumption patterns that may contribute to an increase in the demand for less expensive wines. Specifically, they should focus on new consumption patterns that may arise, adapting the supply chain and defining appropriate marketing strategies to fill new market segments. © 2021, Emerald Publishing Limited.

Could lockdown increase the incidence of eating disorders?

IntroductionSpanish Governmen declared state of emergency in March 2020 to prevent coronavirus COVID-19 from spreading. During September and October 2020, at Child and Adolescent Psychiatry Unit we have attended patients who presented altered eating behaviors whose onset was during lockdown. We report a series of seven cases of adolescent girls between the ages of 11 and 16, who had no previous history of mental illness. During lockdown, they have presented restriction of food and increased physical exercise, with weight loss. Some of these patients have also presented food binges and purging behaviors.ObjectivesReview the impact of lockdown on eating behavior, specially on weight loss.MethodsLiterature review of scientific papers searching in Pubmed.ResultsThere are articles that study the variations in eating habits and exercise ocurred during confinement. Most focus on two trends: on the one hand, increased intake and the tendency to a more sedentary life;on the other hand, the worsening of people with a previous diagnosis of eating disorder. However, there is a third trend for which there are few studies: the new appearance of restrictive eating behaviors, together with increased physical exercise, bingeing and purging. This is the case of the patients we present. These studies describe as a possible cause of these alterations that confinement is a novel situation, which generates stress, social isolation, boredom, anxiety and a feeling of loneliness, which can influence self-concept and eating behaviors.ConclusionsLockdown has favored a change in eating habits and exercise. More studies are needed on new-onset eating disorders.

A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. TRIAL DESIGN: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm. PARTICIPANTS: The study will be performed at the Institut Català d'Oncologia, a tertiary level oncological referral center in the Catalonia region (Spain). The eligibility criteria are: patients > 18 years affected by oncological diseases; ECOG performance status < 2 (Karnofsky score > 60%); a laboratory confirmed infection with SARS-CoV-2 by means of real -time PCR; radiological signs of low respiratory tract disease; absence of organ dysfunction (a total bilirubin within normal institutional limits, AST/ALT≤2.5 X institutional upper limit of normal, alkaline phosphatase ≤2.5 X institutional upper limit of normal, coagulation within normal institutional limits, creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal); absence of HIV infection; no active or latent HBV or HCV infection. The exclusion criteria are: patients with oncological diseases who are not candidates to receive any active oncological treatment; hemodynamic instability at time of study enrollment; impossibility to receive oral medication; medical history of recent or active pulmonary embolism or deep venous thrombosis or patients at high-risk of suffering them (surgical intervention, immobilization); multi organ failure, rapid worsening of respiratory function with requirement of fraction of inspired oxygen (FiO2) > 50% or high-flow nasal cannula before initiation of study treatment; uncontrolled intercurrent illness (ongoing or severe active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements); allergy to one or more of study treatments; pregnant or breastfeeding women; positive pregnancy test in a pre-dose examination. Patients should have the ability to understand, and the willingness to sign, a written informed consent document; the willingness to accept randomization to any assigned treatment arm; and must agree not to enroll in another study of an investigational agent prior to completion of Day +28 of study. An electronic Case Report Form in the Research Electronic Data Capture (REDCap) platform will be used to collect the data of the trial. Removal from the study will apply in case of unacceptable adverse event(s), development of an intercurrent illness, condition or procedural complication, which could interfere with the patient's continued participation and voluntary patient withdrawal from study treatment (all patients are free to withdraw from participation in this study at any time, for any reasons, specified or unspecified, and without prejudice). INTERVENTION AND COMPARATOR: Treatment will be administered on an inpatient basis. We will compare the experimental treatment with baricitinib plus the institutional standard of care compared with the standard of care alone. During the phase I, we will define the dose-limiting toxicity of baricitinib and the dose to be used in the phase 2 part of the study. The starting baricitinib dose will be an oral tablet 4 mg-once daily which can be reduced to 2 mg depending on the observed toxicity. The minimum duration of therapy will be 5 days and it can be extended to 7 days. The standard of care will include the following therapies. Antibiotics will be individualized based on clinical suspicion, including the management of febrile neutropenia. Prophylaxis of thromboembolic disease will be administered to all participants. Remdesivir administration will be considered only in patients with severe pneumonia (SatO2 <94%) with less than 7 days of onset of symptoms and with supplemental oxygen requirements but not using high-flow nasal cannula, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In the randomized phase, tocilizumab or interferon will not be allowed in the experimental arm. Tocilizumab can be used in patients in the standard of care arm at the discretion of the investigator. If it is prescribed it will be used according to the following criteria: patients who, according to his baseline clinical condition, would be an ICU tributary, interstitial pneumonia with severe respiratory failure, patients who are not on mechanical ventilation or ECMO and who are still progressing with corticoid treatment or if they are not candidates for corticosteroids. Mild ARDS (PAFI <300 mmHg) with radiological or blood gases deterioration that meets at least one of the following criteria: CRP >100mg/L D-Dimer >1,000µg/L LDH >400U/L Ferritin >700ng/ml Interleukin 6 ≥40ng/L. The use of tocilizumab is not recommended if there are AST/ALT values greater than 10 times the upper limit of normal, neutrophils <500 cells/mm3, sepsis due to other pathogens other than SARS-CoV-2, presence of comorbidity that can lead to a poor prognosis, complicated diverticulitis or intestinal perforation, ongoing skin infection. The dose will be that recommended by the Spanish Medicine Agency in patients ≥75Kg: 600mg dose whereas in patients <75kg: 400mg dose. Exceptionally, a second infusion can be assessed 12 hours after the first in those patients who experience a worsening of laboratory parameters after a first favourable response. The use of corticosteroids will be recommended in patients who have had symptoms for more than 7 days and who meet all the following criteria: need for oxygen support, non-invasive or invasive mechanical ventilation, acute respiratory failure or rapid deterioration of gas exchange, appearance or worsening of bilateral alveolar-interstitial infiltrates at the radiological level. In case of indication, it is recommended: dexamethasone 6mg/d p.o. or iv for 10 days or methylprednisolone 32mg/d orally or 30mg iv for 10 days or prednisone 40mg day p.o. for 10 days. MAIN OUTCOMES: Phase 1 part: to describe the toxicity profile of baricitinib in COVID19 oncological patients during the 5-7 day treatment period and until day +14 or discharge (whichever it comes first). Phase 2 part: to describe the number of patients in the experimental arm that will not require mechanical oxygen support compared to the standard of care arm until day +14 or discharge (whichever it comes first). RANDOMISATION: For the phase 2 of the study, the allocation ratio will be 1:1. Randomization process will be carried out electronically through the REDcap platform ( https://www.project-redcap.org/ ) BLINDING (MASKING): This is an open label study. No blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The first part of the study (safety run-in cohort) will consist in the enrollment of 6 to 12 patients. In this population, we will test the toxicity of the experimental treatment. An incidence of severe adverse events grade 3-4 (graded by Common Terminology Criteria for Adverse Events v.5.0) inferior than 33% will be considered sufficient to follow with the next part of the study. The second part of the study we will perform an interim analysis of efficacy at first 64 assessed patients and a definitive one will analyze 128 assessed patients. Interim and definitive tests will be performed considering in both cases an alpha error of 0.05. We consider for the control arm this rate is expected to be 0.60 and for the experimental arm of 0.80. Considering this data, a superiority test to prove a difference of 0.20 with an overall alpha error of 0.10 and a beta error of 0.2 will be performed. Considering a 5% of dropout rate, it is expected that a total of 136 patients, 68 for each study arm, will be required to complete study accrual. TRIAL STATUS: Version 5.0. 14th October 2020 Recruitment started on the 16th of December 2020. Expected end of recruitment is June 2021. TRIAL REGISTRATION: AEMPs: 20-0356 EudraCT: 2020-001789-12, https://www.clinicaltrialsregister.eu/ctr-search/search (Not publically available as Phase I trial) Clinical trials: BARCOVID19, https://www.clinicaltrials.gov/ (In progress) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."

Encephalopathies liees au COVID-19 : apport de la TEP-FDG cerebrale dans une serie de 4 cas.

Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2020

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.