54 research outputs found

    Communication and virtual visiting for families of patients in intensive care during the COVID-19 pandemic:A UK National Survey

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    © 2021 by the American Thoracic Society. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0.https://creativecommons.org/licenses/by-nc-nd/4.0/Rationale: Restriction or prohibition of family visiting intensive care units (ICUs) during the coronavirus disease (COVID-19) pandemic poses substantial barriers to communication and family- and patient-centered care. Objectives: To understand how communication among families, patients, and the ICU team was enabled during the pandemic. The secondary objectives were to understand strategies used to facilitate virtual visiting and associated benefits and barriers. Methods: A multicenter, cross-sectional, and self-administered electronic survey was sent (June 2020) to all 217 UK hospitals with at least one ICU. Results: The survey response rate was 54%; 117 of 217 hospitals (182 ICUs) responded. All hospitals imposed visiting restrictions, with visits not permitted under any circumstance in 16% of hospitals (28 ICUs); 63% (112 ICUs) of hospitals permitted family presence at the end of life. The responsibility for communicating with families shifted with decreased bedside nurse involvement. A dedicated ICU family-liaison team was established in 50% (106 ICUs) of hospitals. All but three hospitals instituted virtual visiting, although there was substantial heterogeneity in the videoconferencing platform used. Unconscious or sedated ICU patients were deemed ineligible for virtual visits in 23% of ICUs. Patients at the end of life were deemed ineligible for virtual visits in 7% of ICUs. Commonly reported benefits of virtual visiting were reducing patient psychological distress (78%), improving staff morale (68%), and reorientation of patients with delirium (47%). Common barriers to virtual visiting were related to insufficient staff time, rapid implementation of videoconferencing technology, and challenges associated with family members’ ability to use videoconferencing technology or access a device. Conclusions: Virtual visiting and dedicated communication teams were common COVID-19 pandemic innovations addressing the restrictions to family ICU visiting, and they resulted in valuable benefits in terms of patient recovery and staff morale. Enhancing access and developing a more consistent approach to family virtual ICU visits could improve the quality of care, both during and outside of pandemic conditions.Peer reviewedFinal Published versio

    Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

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    Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10 -8) and rs9275596 (P=6.8 × 10 -10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    The impact of the COVID-19 pandemic on nursing students? navigation of their nursing programmes and experiences of resilience. A qualitative study

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    Introduction : High-quality pre-registration student nurse training and development is integral to developing a sustainable and competent global nursing workforce. Internationally, student nurse recruitment rates have increased since the onset of the COVID-19 pandemic; however, attrition rates for student nurses are high. During the pandemic, many student nurses considered leaving the programme due to academic concerns, feeling overwhelmed, and doubting their clinical skills. Little was known about the extent to which nursing education prior to COVID-19 had prepared students for their role in managing the healthcare crisis or the impact on their resilience. Thus, this study aimed to explore how the COVID-19 pandemic impacted on the resilience levels of student nurses across the United Kingdom. Methods : Data were collected as part of a multi-site qualitative study named ‘COV-ED Nurse’ and involved pre-placement surveys, placement diaries, and post-placement interviews with nursing students. Student nurse participants were recruited from across the United Kingdom, from all years of study, and from all four nursing branches: children, adult, mental health, and learning disabilities. Participants were asked to complete a pre-placement survey that collected demographic details and information about their placement expectations. They were also asked to record a weekly audio-visual or written diary to describe their placement experiences, and, on completion of their placements, students were interviewed to explore their experiences of this time. Data were thematically analysed using the Framework Approach. Ethical approvals were obtained. Results : Two hundred and sixteen students took part in the wider study. The current study involved a subset of 59 students’ data. Four main themes were identified: ‘coping with increased levels of acuity’, ‘perceived risks of the pandemic’, ‘resilience when facing uncertainty and isolation’, and ‘the importance of coping mechanisms and support structures.’ Discussion : From this study, we have generated insights that can be applied to nursing research, education, policy, and practice and identified the wide-ranging impact that the COVID-19 pandemic had on student nurses and their abilities to remain resilient in an unstable environment. The value of communication and support networks from a wide range of sources was highlighted as key to navigating many uncertainties. In addition, the extent to which students were able to navigate their personal and professional roles and identities influenced their ability to cope with and continue along their training pathways

    Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

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    Prostaglandin F2α (PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2α synthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2α biosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2α but expressed different biosynthetic isozymes. In chromaffin cells, PGF2α secretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2α secretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2α release and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2α receptor was only detected in chromaffin cells, making medulla the primary target of PGF2α action. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2α repressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2α may be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cell-specific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal

    Correction to: Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP): a feasibility study

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    Background Progression of dental caries can result in irreversible pulpal damage. Partial irreversible pulpitis is the initial stage of this damage, confined to the coronal pulp whilst the radicular pulp shows little or no sign of infection. Preserving the pulp with sustained vitality and developing minimally invasive biologically based therapies are key themes within contemporary clinical practice. However, root canal treatment involving complete removal of the pulp is often the only option (other than extraction) given to patients with irreversible pulpitis, with substantial NHS and patient incurred costs. The European Society of Endodontology’s (ESE 2019) recent consensus statement recommends full pulpotomy, where the inflamed coronal pulp is removed with the goal of keeping the radicular pulp vital, as a more minimally invasive technique, potentially avoiding complex root canal treatment. Although this technique may be provided in secondary care, it has not been routinely implemented or evaluated in UK General Dental Practice. Method This feasibility study aims to identify and assess in a primary care setting the training needs of general dental practitioners and clinical fidelity of the full pulpotomy intervention, estimate likely eligible patient pool and develop recruitment materials ahead of the main randomised controlled trial comparing the clinical and cost-effectiveness of full pulpotomy compared to root canal treatment in pre/molar teeth of adults 16 years and older showing signs indicative of irreversible pulpitis. The feasibility study will recruit and train 10 primary care dentists in the full pulpotomy technique. Dentists will recruit and provide full pulpotomy to 40 participants (four per practice) with indications of partial irreversible pulpitis. Discussion The Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP) study will address the lack of high-quality evidence in the treatment of irreversible pulpitis, to aid dental practitioners, patients and policymakers in their decision-making. The PIP feasibility study will inform the main study on the practicality of providing both training and provision of the full pulpotomy technique in general dental practice. Trial registration ISRCTN Registry, ISRCTN17973604. Registered on 28 January 2021. Protocol version Protocol version: 1; date: 03.02.202

    Erratum to: Methods for evaluating medical tests and biomarkers

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    [This corrects the article DOI: 10.1186/s41512-016-0001-y.]

    A many-analysts approach to the relation between religiosity and well-being

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    The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

    Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

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    Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy
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