Clinical Ethics Committee Research Articles

IMPACT OF COVID-19 ON MENTAL HEALTH OF HEALTHCARE WORKERS DURING PANDEMIC; AN EXPERIENCE AT A TERTIARY CARDIAC CARE SET UP

Objective: To assess the frequency of mental health problems among healthcare workers related to COVID-19 pandemic among health care workers in a tertiary cardiac care center.Study Design: Descriptive cross sectional study.Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology/ National Institute of Heart Diseases (AFIC/NIHD) Rawalpindi (Pakistan) from Apr 2020 to Jun 2020.
 Methodology: This study was a hospital-based cross-sectional study consisted of 100 healthcare workers including 50 nurses and 50 doctors who volunteered to enroll in our study were included. Approval from the clinical research ethics committee of cardiac care hospital was received before the initiation of this study. Verbal informed consent was provided by all study participants prior to their enrollment. Exclusion criteria comprised of the healthcare workers who refused to participate in it. This study followed the COVID-19 Pandemic Mental Health Questionnaire (CoPaQ) 14. Descriptive statistics were used to describe the percentages and frequencies. Descriptive statistics were used to describe the percentages and frequencies were calculated and analyzed using the Statistical Package for the Social Sciences (SPSS), version 23.0.
 Results: A total of 100 healthcare workers completed the survey. Mean age of the healthcare workers was 36.5 ± 27.0 years (median=36.00), and 75 (75%) were women and men comprised 25 (25%). Of all participants, 50 (50.0%) were nurses, and 50 (50%) were doctors. A considerable proportion of participants reported symptoms of COVID19, 6 (6.0%), tested positive 14 (14%), currently quarantine 24 (24.0%). While 12 healthcare workers experienced 14 day quarantine time period. 16 healthcare workers reported COVID test positive of their closed one. The fear of infecting others with COVID-19 was found to be 30 (30%). The mental stress that that COVID-19 will personally affect us was found in 28 (28%) of healthcare workers. The fear that consequences of the COVID-19 will be severe health disasters was found in 40 (40%) of the individuals.
 Conclusion: In this study of physicians and nurses in hospitals with wards for patients with COVID-19, health care workers responding to the spread of COVID-19 reported high rates of symptoms of anxiety, fear, and distress.

Considerazioni medico-legali sulla mozione del Comitato Nazionale per la Bioetica sull’accanimento clinico nei confronti di bambini con limitate aspettative di vita

The motion approved by the Italian National Bioethics Committee January 30th,2020, entitled “Aggressive treatments or unreasonable obstinacy in medical care of children with short life expectancy”, sets out 12 recommendations for physicians who take care of these children and have the duty to communicate with their parents. The intent of this motion is to give the family the necessary information and support during the decision-making process. Each recommendation is analytically commented. Recommendation 1 advocates the adoption of shared decision-making by the entire healthcare team; promotes the relief of pain and suffering; inhibits disproportionate and ineffective medical treatments; opposes a defensive medicine. Recommendation 2 asks for the promulgation of a national law that establishes clinical ethics committees in Children’s Hospitals. Recommendation 3 implies that parents or legal guardians should be involved in the decision-making process of physicians and clinical ethics committees. Recommendation 4 states that a second opinion may be requested by both the parents and the physicians. Recommendation 5 admits an appeal to the judge in the event of an irreconcilable conflict between the health care team and the family. Recommendation 6 endorses the medical accompaniment of the dying patient, also by means of continuous deep sedation and analgesia. Recommendation 7 enunciates the principle that patients shall have the right to access to palliative care. Recommendation 8 confirms the necessity to strengthen research focused on pediatric pain and suffering. Recommendation 9 excludes that excessive medical treatment may be justified by the need to carry out experiments or research projects. Recommendation 10 concerns the training of physician, other healthcare workers and psychologists in order to support children’s parents both emotionally and practically. Recommendation 11 exhorts to encourage the interaction between parents and seriously ill children. Recommendation 12 assigns a prominent role to parents’ associations for ill children.

Thromboembolic Events and Thrombosis With Thrombocytopenia After COVID-19 Infection and Vaccination in Catalonia, Spain

Background: Thromboembolism and thrombocytopenia have emerged as potential adverse events associated with vaccines against SARS-CoV-2. We compared rates of thromboembolism and thrombocytopenia following vaccination with BNT162b2 and ChAdOx1 with expected rates. Rates for people with COVID-19 were estimated to provide context. Methods: Primary care data from Catalonia, Spain, informed the analysis. Study participants were vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-19/05/2021), diagnosed with COVID-19 (1/09/2020-1/03/2021) or present as of 1/01/2017. Outcomes included venous thromboembolism (VTE), arterial thromboembolism (ATE), thrombocytopenia, and thrombosis with thrombocytopenia syndrome (TTS). Incidence rates were estimated in the 21 and 90 days after vaccination and COVID-19 diagnosis, respectively, and up to 31/03/2019 for background rates. Age indirectly standardised incidence ratios (SIR) were estimated. Findings: We included 945,941 BNT162b2 (778,534 with 2 doses), 426,272 ChAdOx1, 222,710 COVID-19, and 4,570,149 background participants. SIRs for VTE were 1.29 [95% CI 1.13-1.48] and 0.90 [0.76-1.07] after first- and second-dose BNT162b2, and 1.15 [0.83-1.58] after first-dose ChAdOx1. The SIR for VTE in COVID-19 was 8.04 [7.37-8.78]. SIRs for thrombocytopenia were 1.35 (1.30-1.41) and 1.19 (1.14-1.25) after first- and second-dose BNT162b2, 1.03 (0.93-1.14) after first-dose ChAdOx1 and 3.52 (3.39 to 3.67) for COVID-19. Rates of ATE were similar to expected rates for BNT162b2 and ChAdOx1, as were rates of TTS for BNT162b2, while fewer than 5 such events were seen for ChAdOx1. Interpretation: Safety profiles of BNT162b2 and ChAdOx1 were similar. A safety signal was seen for VTE after first-dose of BNT162b2. Although confidence intervals were wider, a similar estimate was seen for first-dose of ChAdOx1. The 1.3 fold increase in the rate of VTE after first-dose of BNT162b2 compared with an 8 fold increase after diagnosis of COVID-19. No safety signals were seen for ATE or TTS. Further research is needed to investigate the causality in the observed associations. Funding Information: This study was funded by the European Medicines Agency in the form of a competitive tender (Lot ROC No EMA/2017/09/PE). Declaration of Interests: DPA’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, from Amgen, Chiesi, and from UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen and UCB Biopharma. Peter Rijnbeek works for a research institute who receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, GSK, Amgen, UCB, Novartis, Astra-Zeneca, Chiesi, Janssen Research and Development, none of which relate to the content of this work. Katia Verhamme works for a research institute who receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, GSK, Amgen, UCB, Novartis, Astra-Zeneca, Chiesi, none of which relate to the content of this work .All other authors have no conflicts of interest to declare.Ethics Approval Statement: This study was approved by the Clinical Research Ethics Committee of the IDIAPJGol (project code: 21/054-PCV).

The analysis of emergency medicine professionals' occupational anxiety during the COVID-19 pandemic

Objectives: People worldwide have experienced anxiety during the COVID-19 pandemic including healthcare professionals. News about the number of deaths and cases shared on social media has also increased the anxiety. Anxiety is described as an emotional state in which a feeling of weakness is experienced during preparation for perceived risk; it also includes fear. In our study, the occupational anxiety levels of emergency medicine professionals were compared based on various variables (institution, years of experience, number of daily emergency patient cases in the institution, etc.). Methods: The study was conducted with 168 emergency medical professionals from 5 different countries. The COVID-19 outbreak was ongoing while data was being collected, and the study was approved by the Clinical Research Ethics Committee provided that the data were collected online. Research data were obtained in June, July, and August 2020. One of the two sub-factors in the scale is physical, physical, and life anxiety factor. There are 12 items in this sub-factor: The lowest possible score is 12, and the highest score is 60. The other sub-factors are the work environment, employees, equipment, and environmental factors. Results: Accessibility to personal protective equipment during the COVID-19 pandemic caused a difference in bodily, physical, and vital anxiety levels (P < 0.05). Gender, chronic disease before COVID-19 status, marital status, years of experience, overtime work during the COVID-19 pandemic, and SARS-COV-2 contagion status during the treatment process did not cause any difference in bodily, physical, and vital anxiety levels (P > 0.05). The place of work caused a significant difference in the level of bodily, physical, and vital anxiety (P < 0.05). Years of experience in the profession caused a significant difference in the level of anxiety regarding work atmosphere, employee, PPE, and environmental factors (P < 0.05). During the COVID-19 pandemic, overtime work during the COVID-19 pandemic caused a significant difference in the level of anxiety related to work atmosphere, employee, equipment, and environmental factors (P < 0.05). Conclusions: During the COVID-19 pandemic, the emergency service working hours caused a significant difference in the anxiety levels related to work atmosphere, employees, equipment, and environmental factors. During the COVID-19 pandemic, access to personal protective equipment caused a difference in anxiety levels. As a result, the anxiety level of the emergency medicine professionals who are in the front line in the hospitals should be treated, and they should be provided psychological and behavioural support.

Early Detection of Aortic Dissection On Non-Contrast CT: The Combination of Deep Learning and Morphologic Characteristics

Background: Identification of the Aortic dissection (AD) at baseline plays a crucial role in clinical practice. Non-contrast CT scans are widely available, convenient, and easy to perform. However, the detection of AD on non-contrast CT scans by radiologists is lack of sensitivity and suboptimal at present. Methods: A total of 452 patients underwent aortic CT angiography (CTA) were enrolled retrospectively from two medical centers in China to form an internal cohort (341 patients, 139 AD, 202 non-AD) and an external testing cohort (111 patients, 46 AD, 65 non-AD). The internal cohort was divided into the training cohort (n=238), validation cohort (n=35) and internal testing cohort (n=68). The morphologic characteristics were extracted from the aortic segmentation. A Gaussian Naive Bayes model integrating the deep-learning model score and the morphologic characteristics were built to differentiate AD from non-AD. The areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to evaluate the model performance. The proposed model was also compared with the subjective assessment of radiologists. Findings: After the combination of all morphologic characteristics, our proposed model significantly outperformed the deep-learning model (AUC: 0. 948 vs. 0.803 on the internal testing cohort, 0.969 vs. 0.814 on the external testing cohort, both p 0.05). Interpretation: The proposed model presented good performance on the AD detection on non-contrast CT scans, thus early diagnosis as well as prompt treatment would be available. Funding Information: CAMS Innovation Fund for Medical Sciences (CIFMS); the Major International (Regional) Joint Research Project of National Natural Science Foundation of China; the National Natural Science Foundation of China; the National Key Research and Development Program of China; the China Postdoctoral Science Foundation. Declaration of Interests: All the other authors have no conflict of interest to disclose. Ethics Approval Statement: This study was reviewed and approved by the local clinical institutional ethics committees of the two centers involved, and informed consent was waived because of the retrospective nature of this study.

Determinants of Carbon Load in Airway Macrophages in Pregnant Women

Background: The available evidence on determinants of personal exposure to air pollution in low and middle-income countries is very scarce. Moreover, although airway macrophages carbon loading (AMCL) has been suggested to be a biomarker of the long-term exposure to air pollution, to date no study has characterized AMCL for the pregnancy period. Therefore, this study aimed to assess the determinants of AMCL during pregnancy in Iran, a middle-income country. Methods: This study was based on a sample of 234 pregnant women with term and normal vaginal delivery who were residing in Sabzevar, Iran (2019). Image analysis was applied to calculate the carbon area (µm 2 ) in airway macrophages as an indicator of AMCL. For each participant, we characterized 35 potential determinants of personal exposure to air pollution including six personal, nine indoor, and 20 home-outdoor factors. We applied Deletion/Substitution/Addition algorithm to identify the most relevant determinants that could predict AMCL levels. Findings: The median (IQR) of AMCL level was 0·12 (0·30) µm 2 with a successful sputum induction in 82·9% (194) of participants. Ambient residential PM 2·5 levels was positively associated with higher AMCL levels. On the other hand, increased residential distance to the traffic lights, squares and ring-roads, the duration of opening window per day, and opening window during cooking were inversely associated with AMCL levels. Interpretation: Our findings provide novel insights on the different personal, indoor, and outdoor determinants of personal exposure to air pollution during pregnancy in a middle-income country. Funding: This study was supported by a research grant awarded by the Sabzevar University 55 of Medical Sciences [Grant number: 95075]. Declaration of Interest: We declare no competing interests. Ethical Approval: The Clinical Research Ethical Committee of Sabzevar University of Medical Sciences approved our study (IR.MEDSAB.REC.1395.82)

Predictors of Dropout in a Cohort of People Undergoing Treatment for Borderline Personality Disorder in a Public Community Mental Health Service: A Time-to-Event Analysis

Background: Dialectical Behaviour Therapy (DBT) is an effective evidence based treatment for Borderline Personality Disorder (BPD). However, irrespective of the success of the treatment, a dropout rate of approximately 30%-40% is regarded as the norm. In this analysis we aimed to investigate whether early predictors of dropout can be identified from baseline data. Methods: Between 2014 and 2017, data was collected from 196 participants at multiple timepoints as part of a coordinated multisite study of standard DBT treatment for community based service users being treated for BPD in Ireland. Dropout was strictly defined as per the standard DBT programme four-miss rule. For this analysis data were censored at 48 weeks and risk factors for dropout were identified using a Cox proportional hazards model that adjusted for age and gender. Engagement with phone coaching in the first month was examined as a time dependant covariate. Outcomes: Of the 196 participants, 12 (6%) were censored and 9 (4%) removed leaving 187 for analysis of whom, 109 (58%) completed and 66 (32%) dropped out. Results from univariable Cox proportional hazard regressions found off-label use of anti-psychotic medication was associated with an increased risk of drop-out, while full time employment status, receipt of disability support and engagement with phone coaching in the first month were associated with a reduced risk of dropout. Entering these variables in a multivariable Cox proportional hazard regression found off-label use of anti-psychotic medication (adjusted HR 2·69, 95% CI 1·50 - 4·83; p=0·001); full time employment status (adjusted HR 0.23, 95% CI 0.07-0.77; p=0.02) and disability (adjusted HR 0.20, 95% CI 0.05-0.85; p=0.03) remained significant predictors. Interpretation: Awareness of employment status and off-label prescription of anti-psychotic medication at baseline as significant risk factors for dropout may provide clinicians with valuable insight when starting treatment and could potentially inform treatment approach. Funding Information: This work, as part of the The National DBT Project, was funded by the Irish Health Service Executive (HSE) and the National Office for Suicide Prevention (NOSP). The fund is administered via the National Suicide Research Foundation (NSRF). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: All procedures were reviewed and approved by the following research ethics committees: Clinical Research Ethics Committee of the Cork University Teaching Hospitals, Galway Clinical Research Ethics Committee, HSE Mid Western Regional Hospital Research Ethics Committee, HSE North East Area Research Ethics Committee, HSE South East Area Research Ethics Committee, Linn Dara & Beechpark Ethics Committee; Naas General Hospital Ethics Committee; Saint John of God Hospitaller Ministries Research Ethics Committee and Sligo General Hospital Research Ethics Committee.

Induction of Beneficial Changes in Glucose Homeostasis, Lipid Profile, Inflammation, Retinopathy, Bile Acids and Gut Microbiota in Streptozotocin-Induced Type 1 Diabetes Mellitus by Essential Fatty Acids

Background: Essential fatty acids (EFAs) n3 alpha-linolenic acid (ALA) and n6 linoleic acid (LA) have been shown to improve lipid metabolism, promote nervous system development, suppress inflammation, and are of benefit in diabetes mellitus and cancer. But the exact mechanism of their action(s) is not clear. In the present study, we evaluated the effects of ALA and LA on glucose homeostasis, circulating lipid profile, inflammatory markers, gut microbiome, and bile acids in streptozotocin (STZ)-induced type 1 diabetes with retinopathy in rats. We also measured vitreal LXA4 levels in patients with diabetic retinopathy since arachidonic acid (AA), the precursor of LXA4, is derived from LA. Methods: The study was performed in male Sprague Dawley rats. Type 1 DM was induced by intraperitoneal injection of STZ. The type 1 DM animals received LA or ALA 100 ug/day via intraperitoneal route on alternate days till the end of the study (21 days after the DM onset). In these animals, glucose homeostasis and lipid profile were evaluated. Plasma and retinal fatty acid profile by gas chromatography (GC), retinal histology by H&E staining, activities of desaturases in the retina and liver tissues and inflammatory markers by qRT-PCR, and composition of the gut microbiota by 16S rDNA sequencing technology of the fecal samples were performed. In addition, short-chain fatty acids (SCFAs) and bile acids (BAs) in the feces and liver of rats were assayed by GC and liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS), respectively. Human vitreal samples obtained from patients with proliferative diabetic retinopathy (PDR) were analyzed for their fatty acids profile and LXA4 levels and compared with those with macular hole (control). Findings: LA and ALA-treated STZ-induced type 1 DM animals showed significant reduction in their plasma glucose levels, pro-inflammatory cytokines (IL-6 and TNF-α), changes in the composition of gut microbiome in the form of an increase in the abundance of Ruminococcaceae (ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010 and Ruminococcus_1 (in LA-treated group) , an increase in acetic acid and butyric acid, and an increase in the fecal concentrations of CA, CDCA and TUDCA and a decrease in GCA. Concentrations of hepatic CDCA, TCDCA, and TUDCA were significantly increased in ALA treated animals while CDCA were elevated in those with LA treatment. STZ-treated animals showed significant decrease in plasma LA, GLA, and AA and ALA levels with no significant changes in retinal fatty acid composition. All these changes reverted to normal in LA and ALA treated group. The changes in the plasma fatty acid composition were accompanied by significant alterations in the expression of desaturases, COX-2 and 5-LOX and 12-LOX enzymes and pro- and anti-inflammatory cytokines. In addition, retinal LXA4 levels were found to be decreased in patients with PDR. Interpretation: The results of the present study suggest that ALA and LA administration can improve plasma glucose levels, suppress inflammation, and produce significant beneficial alterations in the gut microbiota, plasma lipid profile and EFAs metabolism. Decrease in retinal LXA4 levels in those with PDR agree with the suggestion that EFAs metabolism is altered in T1DM and DR. These results imply a significant role for EFAs and their metabolites in the pathobiology of type 1 DM and diabetic retinopathy. Funding Information: The project was funded by the National Natural Science Foundation of China (No. 82000886), and Natural Science Foundation of Zhejiang Province (No.LQ20H120011). Declaration of Interests: Authors have no conflicts of interest to declare. Ethics Approval Statement: This study was approved by the animal ethics committee of the Second Affiliated Hospital of Zhejiang University school of medicine. All experimental procedures using animals were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. This study was approved by the Clinical Ethical Research Committee of the Second Affiliated Hospital of Zhejiang University school of medicine. The study was performed as per the tenets of Helsinki declaration. Informed consent obtained from all the participating patients.

Cancer and the Risk of COVID-19 Diagnosis, Hospitalisation, and Death: A Population-Based Multi-State Cohort Study Including 4,618,377 Adults in Catalonia, Spain

Background: The relationship between cancer and COVID-19 infection and severity is poorly understood. We described the associations between cancer and risk of COVID-19 diagnosis, hospitalisation, and COVID-19-related death.Methods: Population-based cohort study between 1 March and 6 May 2020, using electronic health records from the SIDIAP database including ~80% of the population in Catalonia, Spain. Cancer was defined as any primary invasive malignancy excluding non-melanoma skin cancer. We estimated adjusted hazard ratios (aHRs) for the risk of COVID-19 (outpatient) clinical diagnosis, hospitalisation (with or without a prior COVID-19 diagnosis) and COVID-19-related death using Cox proportional hazard regressions. Models were estimated for the overall cancer population and by years since cancer diagnosis (5-years), sex, age, and cancer type (haematological or solid); and adjusted for age, sex, smoking status, deprivation, and comorbidities.Findings: We included 4,618,377 adults, of which 260,667 (5.6%) had a history of cancer. Patients with cancer were older and had more comorbidities than cancer-free patients. A total of 98,951 individuals (5.5% with cancer) were diagnosed and 6,355 (16.4% with cancer) were directly hospitalised (no prior diagnosis) with COVID-19. Of those diagnosed, 6,851 were subsequently hospitalised (10.7% with cancer) and 3,227 died without being hospitalised (18.5% with cancer). Among those hospitalised, 1,963 (22.5% with cancer) died. Cancer was associated with an increased risk of COVID-19 diagnosis (aHR: 1.08; 95% confidence interval [1.05-1.11]); direct COVID-19 hospitalisation (1.33 [1.24-1.43]); and death following a COVID-19 hospitalisation (1.12 [1.01-1.25]). These associations were stronger for patients recently diagnosed with cancer, aged Interpretation: Patients recently diagnosed with cancer, aged Funding: This project was funded by the Health Department from the Generalitat de Catalunya with a grant for research projects on SARS-CoV-2 and COVID-19 disease organized by the Direcció General de Recerca i Innovació en Salut. This project has also received support from the European Health Data and Evidence Network (EHDEN) project. EHDEN received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The University of Oxford received a grant related to this work from the Bill & Melinda Gates Foundation (Investment ID INV-016201), and partial support from the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. ER was supported by Instituto de Salud Carlos III (grant number CM20/00174). DPA is funded through a National Institute for Health Research (NIHR) Senior Research Fellowship (Grant number SRF-2018-11-ST2-004). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: DPA reports grants and others from AMGEN; grants, non-financial support and other from UCB Biopharma; grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants. No other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: This study was approved by the Clinical Research Ethics Committee of the IDIAPJGol (project code: 20/070-PCV)

Single Dose Oral Food Challenge at Diagnosis Accelerates Cows Milk Allergic Infants’ Acquisition of Oral Tolerance to Milk, But Progress is Influenced by Maternal Anxiety

Background: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Parents often display significant anxiety about this condition. Single dose challenges are a new method of assessing dose reactivity in food allergic children. Methods: We recruited children referred for evaluation of CMPA to a randomised, controlled trial of single dose challenge to cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 - before implementation of graded exposure to CM (using the 12 step iMAP Milk Tolerance Induction Ladder) at home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ response/progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion: Using the 12 step iMAP milk ladder accelerates natural tolerance induction in infants under 12 months with CMPA. A supervised single dose at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards tolerance but preexisting high levels of maternal anxiety are associated with poorer progress. Funding: YD was in receipt of a Clinical Research Fellowship from the National Childrens Research Centre Ireland. Declaration of Interest: AM received research funding from Aimmune Therapeutics, RvR declares consultancies for HAL Allergy BV, Citeq BV, Angany Inc, speaker fees from HAL Allergy BV, ThermoFisher Scientific, ALK and stock options from Angany Inc. ADG receives research funding and speaker fees from Aimmune Therapeutics JO’BH receives research funding, speaker fees and consultancy fees from Aimmune Thereputics, research funding and speaker fees from DBV Technologies, research funding from Johnson&Johnson, Clemens von Pirquet Foundation and Temple st Hospital Research Foundation. Ethical Approval: Ethical approval was obtained from the Clinical Research Ethics Committees of the Cork Teaching Hospitals and Crumlin Hospital. Approval was granted on 26th September 2017.

Effects of BNT162b2 mRNA Vaccination on COVID-19 Disease, Hospitalisation and Mortality in Nursing Homes and Healthcare Workers: A Prospective Cohort Study Including 28,594 Nursing Home Residents, 26,238 Nursing Home Staff, and 61,951 Healthcare Workers in Catalonia

Background: Spain began vaccinating priority groups against COVID-19 with BNT162b2 in late December 2020. We report associations of vaccination with COVID-19 infection, hospitalisation, and mortality among nursing home residents, nursing home staff, and healthcare workers. Methods: We analysed three cohorts of all nursing home residents, nursing home staff, and healthcare workers in Catalonia on 27 December 2020. Data were obtained from linked primary care, RT-PCR and lateral flow test, hospital, and mortality records. Those with a pre-study COVID-19 diagnosis or no linked electronic medical records were excluded. Two doses of BNT162b2 were administered 3 weeks apart. Participants were followed until the earliest of an outcome (confirmed COVID-19 infection, hospitalisation, and mortality) or 5 March 2021. Participants could contribute data to the unvaccinated, one-dose, and two-dose groups. Analyses were conducted using time-varying Cox regression. Multivariable adjustment for imbalances in socio-demographics, comorbidity, and polypharmacy. Findings: We included 28,594 nursing home residents, 26,238 nursing home staff, and 61,951 healthcare workers, of whom 2,405, 1,584, and 2,672 received COVID-19 diagnoses; 383, 35, and 76 were hospitalised; and 409, 0, and 1 died. The adjusted hazard ratio (HR) (95% confidence interval) for COVID-19 infection after two-dose vaccination was 0·08 (0·07-0·09) for nursing home residents, 0·12 (0·10-0·15) for nursing home staff, and 0·05 (0·04-0·07) for healthcare workers. The adjusted HRs for hospitalisation and mortality after two-dose vaccination were 0·03 (0·02-0·05) and 0·02 (0·01-0·03), respectively, for nursing home residents. Nursing home staff and healthcare workers recorded insufficient events for mortality analysis. Interpretation Vaccination was associated with 85%-96% reduction in SARS-CoV-2 infection in all three cohorts, and bigger reductions in hospitalisations and mortality amongst nursing home residents for up to two months. More data are needed on the long-term effects of COVID-19 vaccines. Funding: Partially supported by National Institute of Health Research UK, We do not have any other funding acknowledgements.Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Clinical Research Ethics Committee of the IDIAP Jordi Gol with reference number 21/045-PCV.

Influence of Confinement on Patients with Autoimmune and Immune-Mediated Inflammatory Disease Receiving Biological Treatment for COVID-19 Infection. The BIOCOVID Study

Objectives: To assess the rates and severity of SARS-CoV-2 infection in patients with autoimmune and immune-mediated inflammatory disease (AI/IMID) treated with anticytokine biologics (AB) or Janus Kinase inhibitors (JAKi), and to compare the types of confinement observed by AI/IMID patients and the general population.Methodology: A case-control study nested within a retrospective observational study. Subjects: AI/IMID patients followed by rheumatology, dermatology and digestology specialists and who were receiving treatment with AB/JAKi. Controls were selected from our Primary Care Centers. The main outcome was SARS-CoV-2 infection and severity. The secondary outcome was the type of confinement (strict, standard, lax, and no confinement).Results: Three hundred and sixty-seven patients (54·8% men, mean age 52 years) and 193 controls (53·4% men, mean age 52 years). In patients’ group, 95·6% were receiving AB treatment, and 43·3% had at least one risk factor for COVID compared to 37·8% of controls. Cumulative rates of COVID infection were 10·1% in the AI/IMID group and 13·5% in controls (p=0·228). Strict confinement was the most frequent form in both groups; lax confinement was more common in the control group (p=0·013, OR=0·62). There were no differences in the incidence of COVID-19 according to type of confinement.Conclusions: The incidence of COVID-19 infection in our cohort is similar to that reported in other series. None of our patients developed severe COVID-19 infection. We observed that strict confinement was predominant in both groups and was higher in the AI/IMID patients. Lax confinement was more frequent in the control group.Funding: This project has obtained a research grant from the Catalan Society of Rheumatologywhich has allowed the project to be carried out.Declaration of Interest: None to declare. Ethical Approval: The protocol was approved by an independent Clinical Research Ethics Committee (Comitè d'Ètica d'Investigació Clínica de la Fundació Unió Catalana d'Hospitals, protocol number CEIC 20/45).

Family witnessed resuscitation and invasive procedures: Patient and family opinions.

Family presence during invasive procedures and cardiopulmonary resuscitation (FPDR) is a highly controversial issue, with divergence of opinion among health professionals, with clinical evidence in favor, and with barriers to its implementation in comprehensive patient care. Many international organizations support health policies for its implementation, but it is not a widespread practice. Little research has been conducted on this subject from the perspective of patients and families. To learn opinions, perceptions, and desires of family members and patients in terms of family presence during invasive procedures and cardiopulmonary resuscitation. Qualitative descriptive study, using semi-structured interviews with relatives and patients regarding their experiences and perceptions about FPDR (n = 18) from 8 October 2017 to 8 March 2018. The interviews were recorded and transcribed verbatim for later analysis using the method of content analysis. This study has the approval of the Clinical Research Ethics Committee of the Fundació Unió Catalana d'Hospitals and ethical considerations were carefully regarded throughout the study. Three significant categories were identified: knowledge, respect for rights, and accompaniment of the patient, relating FPDR to courage, emotional support, and trust in professionals. FPDR is an unusual practice; it is not offered to patients or their families, and it is not considered a patient's right, although most of the interviewees support it. The desire for accompaniment is conditioned by the courage and knowledge of the accompanying persons, as well as the degree of invasiveness of the procedures. The results of this study provide information for a change of vision in patient-centered care.

Respeto por la autonomía Parte 1

Presentación de un caso de una mujer joven que asiste a una consulta ginecológica y solicita al médico especialista que le practique una tubectomía porque, de común acuerdo con su pareja, no desea tener hijos. El médico se niega aduciendo que la paciente no sabe lo que pide y no es consciente de que en el futuro puede arrepentirse de su decisión. La paciente insiste argumentando que su decisión es fruto de la reflexión y es consistente con su cosmovisión y su estilo de vida, pero el médico se niega a acceder a su solicitud. La paciente acude al comité de ética clínica de la institución pidiendo ayuda. El comité escucha las razones del médico y la paciente y da la razón a esta, por considerar que es una decisión en uso pleno de su autonomía y decide solicitar a un médico especialista en la institución que practique la cirugía a la paciente. Se hace un análisis desde el principio ético de respeto por la autonomía de la actuación del médico especialista y de la paciente.

Effectiveness and cost-effectiveness of a lifestyle modification programme in the prevention and treatment of subclinical, mild and moderate depression in primary care: a randomised clinical trial protocol

IntroductionMajor depression is a highly prevalent pathology that is currently the second most common cause of disease-induced disability in our society. The onset and continuation of depression may be related...

Ethical considerations and challenges in herbal drug trials with the focus on scientific validity and risk assessment.

Scientific validity and risk assessment are two main ethical issues which raise specific challenges and are unique to clinical trials investigating crude extracts/fractions from herbal materials. There are considerable challenges for both clinical investigators and ethics committee members in dealing with such issues, many of them remain unresolved, resulting in a large variation in ethical requirements, justification, and decisions. Despite a remarkable surge in herbal medicine research globally, a number of clinical investigators or even ethics committee members have limited confidence in dealing with related ethical issues. In this article, we extensively review and discuss the two main ethical issues (i.e., scientific validity and risk assessment) and highlight key considerations that are important for ethical review and justification for the conduct of herbal drug trials.

Clinical Ethics Committees in Africa: lost in the shadow of RECs/IRBs?

BackgroundClinical Ethics Committees (CECs) are well established at healthcare institutions in resource-rich countries. However, there is limited information on established CECs in resource poor countries, especially in Africa. This study aimed to establish baseline data regarding existing formal CECs in Africa to raise awareness of and to encourage the establishment of CECs or Clinical Ethics Consultation Services (CESs) on the continent.MethodsA descriptive study was undertaken using an online questionnaire via SunSurveys to survey healthcare professionals and bioethicists in Africa. Data were subjected to descriptive analysis and Fischer's exact test was applied to determine associations. Texts from the open-ended questions were thematically analysed.ResultsIn total 109 participants from 37 African countries completed the survey in December 2019. A significant association was found between participants’ bioethics qualification or training and involvement in clinical ethics (p = 0.005). All participants were familiar with Research Ethics Committees (RECs), and initially conflated RECs with CECs. When CECs were explained in detail, approximately 85.3% reported that they had no formal CECs in their institutions. The constraints to developing CECs included lack of training, limited resources, and lack of awareness of CECs. However, the majority of participants (81.7%) were interested in establishing CECs. Participants listed assistance required in establishing CECs including funding, resources, capacity building and collaboration with other known CECs. The results do not reflect CECs established since the onset of COVID-19 in Africa.ConclusionsThis study provides a first look into CECs in Africa and found very few formal CECs on the continent indicating an urgent need for the establishment of CECs or CESs in Africa. While the majority of healthcare professionals and bioethicists are aware of ethical dilemmas in healthcare, the concept of formal CECs is foreign. This study served to raise awareness of CECs. Research ethics and RECs overshadow CECs in Africa because international funders from the global north support capacity development in research ethics and establish RECs to approve the research they fund in Africa. Raising awareness via educational opportunities, research and conferences about CECs and their role in improving the quality of health care in Africa is sorely needed.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

Identification of Serum Prognostic Biomarkers of Severe COVID-19 by Multi-Layered Quantitative Proteomic Approach

The COVID-19 is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we introduced an innovative approach utilizing data-independent acquisition (DIA) mass spectrometry to identify the serum proteins closely associated with the COVID-19 severity. We observed 23 proteins to be differentially expressed between the cohorts of critically ill COVID-19 patients with adverse and favorable prognosis. Myoglobin (MB), CHI3L1 and IGFALS were found to have a high sensitivity and specificity for their possible use as independent biomarkers to provide information on the disease prognosis. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.Funding: This work was in part supported by grants from the Japan Agency for Medical Research and Development (JP19fk0108169 to YK and JP19fk0108110/JP20he0522001 to AR).Conflict of Interest: The authors declare no competing interests.Ethical Approval: This research plan and protocol was approved by the Clinical Ethics Committee of Yokohama City University Hospital (B2002000048). This study was also performed with the approval of the Clinical Ethics Committee in each of the medical facilities. Informed consent was obtained from all patients and/or their guardians before serum samples collection.

The Motion of the Italian National Bioethics Committee on Aggressive Treatment towards Children with Limited Life Expectancy.

The motion of the Italian National Bioethics Committee entitled “Aggressive treatment or therapeutic obstinacy on young children with limited life expectancy” comprises a premise that rejects therapeutic obstinacy and makes 12 recommendations. Recommendation no. 1 states the general rules: it ascribes a cardinal role to a shared care plan, it supports pain management therapy and pain relief, it opposes ineffective and disproportionate clinical treatment and defensive medicine. The other recommendations are correlated to the enacting of a national law establishing clinical ethics committees in paediatric hospitals; participation of parents and their fiduciaries in the decision-making processes; recourse to courts only as extrema ratio in the event of irremediable disagreement between the medical team and the family members; accompaniment at the end of life also through continuous deep sedation combined with pain therapy; access to palliative care; the need to reinforce research on pain and suffering in children; clinical trials and research studies conducted in children; the training of doctors, healthcare personnel and psychologists, to support parents in emotional and practical terms; the facilitation of the closeness of parents to children in extremely precarious clinical conditions; the relevant role of the associations of parents of sick children. Comments are made, in particular, about the innovative recommendations respectively relating to the adoption of care planning, the establishment, by law, of clinical ethics committees in paediatric hospitals and the limitation of recourse to courts—only as extrema ratio—in the event of irremediable disagreement between the medical team and the family members.