Search

Your search keyword '"Fairbrother, A"' showing total 513 results
Start Over Author "Fairbrother, A" Topic humans
513 results on '"Fairbrother, A"'

1. Non-cancer-related pathogenic germline variants and expression consequences in ten-thousand cancer genomes

Author

Wang, Zishan, Fan, Xiao, Shen, Yufeng, Pagadala, Meghana S, Signer, Rebecca, Cygan, Kamil J, Fairbrother, William G, Carter, Hannah, Chung, Wendy K, and Huang, Kuan-lin

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Clinical Research, Cancer, Genetic Testing, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Alleles, Gene Expression Regulation, Neoplastic, Genomics, Germ Cells, Heterozygote, Inheritance Patterns, Neoplasms, Risk Assessment, Sequence Analysis, DNA, Clinical Sciences
Abstract

BackgroundDNA sequencing is increasingly incorporated into the routine care of cancer patients, many of whom also carry inherited, moderate/high-penetrance variants associated with other diseases. Yet, the prevalence and consequence of such variants remain unclear.MethodsWe analyzed the germline genomes of 10,389 adult cancer cases in the TCGA cohort, identifying pathogenic/likely pathogenic variants in autosomal-dominant genes, autosomal-recessive genes, and 59 medically actionable genes curated by the American College of Molecular Genetics (i.e., the ACMG 59 genes). We also analyzed variant- and gene-level expression consequences in carriers.ResultsThe affected genes exhibited varying pan-ancestry and population-specific patterns, and overall, the European population showed the highest frequency of pathogenic/likely pathogenic variants. We further identified genes showing expression consequence supporting variant functionality, including altered gene expression, allelic specific expression, and mis-splicing determined by a massively parallel splicing assay.ConclusionsOur results demonstrate that expression-altering variants are found in a substantial fraction of cases and illustrate the yield of genomic risk assessments for a wide range of diseases across diverse populations.

Published
2021

2. Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Author

Chen, Zhongbo, Zhang, David, Reynolds, Regina H, Gustavsson, Emil K, García-Ruiz, Sonia, D’Sa, Karishma, Fairbrother-Browne, Aine, Vandrovcova, Jana, Hardy, John, Houlden, Henry, Gagliano Taliun, Sarah A, Botía, Juan, and Ryten, Mina

Subjects
Human Genome, Brain Disorders, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurosciences, Dementia, Biotechnology, Alzheimer's Disease, Neurodegenerative, Aging, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, Neurological, Alzheimer Disease, Apolipoproteins E, Brain, Chromosomes, Human, Pair 19, Conserved Sequence, DNA, Intergenic, Gene Ontology, Genome, Human, Humans, Introns, Linkage Disequilibrium, Molecular Sequence Annotation, Neurodegenerative Diseases, Phenotype, Phylogeny, Polymorphism, Single Nucleotide, RNA, Long Noncoding, RNA, Messenger, Regression Analysis, International Parkinson’s Disease Genomics Consortium
Abstract

Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer's disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.

Published
2021

3. The Development of the Neural Substrates of Cognitive Control in Adolescents with Autism Spectrum Disorders

Author

Solomon, Marjorie, Yoon, Jong H, Ragland, J Daniel, Niendam, Tara A, Lesh, Tyler A, Fairbrother, Wonja, and Carter, Cameron S

Subjects
Biological Psychology, Cognitive and Computational Psychology, Biomedical and Clinical Sciences, Psychology, Clinical Research, Intellectual and Developmental Disabilities (IDD), Behavioral and Social Science, Autism, Neurosciences, Mental Health, Pediatric, Brain Disorders, 1.1 Normal biological development and functioning, 1.2 Psychological and socioeconomic processes, Mental health, Adolescent, Adolescent Development, Brain, Brain Mapping, Child, Child Development Disorders, Pervasive, Cognition, Executive Function, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Adolescence, autism spectrum disorders, cognitive control, development, fMRI, response inhibition, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundAutism spectrum disorders (ASDs) involve impairments in cognitive control. In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay.MethodsWe used event-related functional magnetic resonance imaging and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12-15; n = 13 with ASD and n = 13 with TYP) and older (ages 16-18; n = 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxelwise univariate and task-related functional connectivity analyses.ResultsOlder ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex and the anterior cingulate cortex, bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between dorsolateral prefrontal cortex and parietal cortex (Brodmann areas 9 and 40) was related to task performance in TYP.ConclusionsAdolescents with ASD rely more on reactive cognitive control, involving last-minute conflict detection and control implementation by the anterior cingulate cortex and ventrolateral prefrontal cortex, versus proactive cognitive control requiring processing by dorsolateral prefrontal cortex and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention.

Published
2014

4. Association between regulator of G protein signaling 9-2 and body weight.

Author

Waugh, Jeffrey L, Celver, Jeremy, Sharma, Meenakshi, Dufresne, Robert L, Terzi, Dimitra, Risch, S Craig, Fairbrother, William G, Neve, Rachael L, Kane, John P, Malloy, Mary J, Pullinger, Clive R, Gu, Harvest F, Tsatsanis, Christos, Hamilton, Steven P, Gold, Stephen J, Zachariou, Venetia, and Kovoor, Abraham

Subjects
Nucleus Accumbens, Adipose Tissue, Adipocytes, Animals, Mice, Knockout, Humans, Mice, Rats, Body Weight, Weight Loss, RGS Proteins, Body Mass Index, Motor Activity, RNA Splicing, Sequence Deletion, Base Sequence, Genes, Reporter, Introns, Molecular Sequence Data, Female, Male, Intra-Abdominal Fat, Genetic Association Studies, Genes, Reporter, Knockout, General Science & Technology
Abstract

Regulator of G protein signaling 9-2 (RGS9-2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9-2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9-2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9-2 as a factor in regulating body weight.

Published
2011

5. Conducting school-based health surveys with secondary schools in England: advice and recommendations from school staff, local authority professionals, and wider key stakeholders, a qualitative study

Author

Hatch, Lorna M., Widnall, Emily C., Albers, Patricia N., Hopkins, Georgina L., Kidger, Judi, de Vocht, Frank, Kaner, Eileen, van Sluijs, Esther M. F., Fairbrother, Hannah, Jago, Russell, Campbell, Rona M., Van Sluijs, Esther [0000-0001-9141-9082], and Apollo - University of Cambridge Repository

Subjects
Schools, Adolescent, Research, Well-being, Health Surveys, Retention, Health, Surveys and Questionnaires, Educational Status, Humans, Recruitment, Students, Young People, School Health Services
Abstract

Background: Improving the health and well-being of young people is a public health priority. Schools present an ideal setting to implement strategies to improve young people’s health and well-being. A key strategy involves conducting surveys to assess student health needs, inform interventions, and monitor health over time. Conducting research in schools is, however, challenging. Schools can find it difficult to participate and adhere to research processes, even when they are keen to be involved in research, because of competing priorities (e.g., attendance and educational achievement), as well as time and resource constraints. There is a lack of literature on the perspectives of school staff and other key stakeholders working in young people’s health on how best to work with schools to conduct health research, and in particular, health surveys. Methods: Participants (n = 26) included members of staff from 11 secondary schools (covering students aged 11–16 years), 5 local authority professionals, and 10 wider key stakeholders in young people's health and well-being (e.g., a school governor, a national government member), based in South West England. Participants took part in semi-structured interviews that were conducted either over the phone or via an online platform. Data were analysed using the Framework Method. Results: Three main themes were identified: Recruitment and Retention, Practicalities of Data Collection in Schools, and Collaboration from Design to Dissemination. It is important to acknowledge the role of local authorities and academy trusts in the English education system, and work closely with these when conducting school-based health surveys. School staff prefer to be contacted about research via email and in the summer term, following exams. Researchers should contact a member of staff involved in student health/well-being, as well as senior leadership, during recruitment. Data collection during the start and end of the school year is undesirable. Research should be collaborative with school staff and young people, consistent with school priorities and values, and flexible and tailored to school timetables and resources. Conclusions: Overall the findings demonstrate that survey-based research methods should be school-led and tailored to each school.

Published
2023

6. Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study

Author

Dave, Rajiv V, Elsberger, Beatrix, Taxiarchi, Vicky P, Gandhi, Ashu, Kirwan, Cliona C, Kim, Baek, Camacho, Elizabeth M, Coles, Charlotte E, Copson, Ellen, Courtney, Alona, Horgan, Kieran, Fairbrother, Patricia, Holcombe, Chris, Kirkham, Jamie J, Leff, Daniel R, McIntosh, Stuart A, O'Connell, Rachel, Pardo, Ricardo, Potter, Shelley, Rattay, Tim, Sharma, Nisha, Vidya, Raghavan, Cutress, Ramsey I, B-MaP-C Study Collaborative, Dave, Rajiv V [0000-0001-6827-8090], and Apollo - University of Cambridge Repository

Subjects
Cohort Studies, Ki-67 Antigen, Breast cancer, Humans, COVID-19, Female, Breast Neoplasms, Neoadjuvant endocrine therapy, Prognosis, Pandemics, Bridging endocrine therapy, Neoadjuvant Therapy
Abstract

PURPOSE: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources. METHODS: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb-July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis. RESULTS: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32-81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7-8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months' treatment duration; median of 4 mm [IQR - 20, 4]. In a small subset of patients (n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month's duration of BrET. DISCUSSION: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials.

Published
2023

7. Creation of a Pilot School Health Research Network in an English Education Infrastructure to Improve Adolescent Health and Well-Being: A Study Protocol

Author

Catherine A. Sharp, Emily Widnall, Patricia N. Albers, Kate Willis, Colin Capner, Judi Kidger, Frank de Vocht, Eileen Kaner, Esther M. F. van Sluijs, Hannah Fairbrother, Russell Jago, Rona Campbell, Sharp, Catherine A. [0000-0002-7311-3933], Widnall, Emily [0000-0002-7107-562X], Albers, Patricia N. [0000-0001-5710-8483], Capner, Colin [0000-0001-7179-3755], de Vocht, Frank [0000-0003-3631-627X], Fairbrother, Hannah [0000-0001-9347-8625], Jago, Russell [0000-0002-3394-0176], Apollo - University of Cambridge Repository, Sharp, Catherine A [0000-0002-7311-3933], and Albers, Patricia N [0000-0001-5710-8483]

Subjects
school health research network, Schools, systems intervention, Adolescent, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Adolescent Health, Students/psychology, well-being, School Nursing, Humans, Educational Status, adolescence, Child, Students, mental health, School Health Services
Abstract

Peer reviewed: True, Schools play a significant role in promoting health and well-being and the reciprocal links between health and educational attainment are well-evidenced. Despite recognition of the beneficial impact of school-based health improvement programmes, significant barriers to improving health and well-being within schools remain. This study pilots a School Health Research Network in the South West of England (SW-SHRN), a systems-based health intervention bringing together schools, academic health researchers and public health and/or education teams in local authorities to share knowledge and expertise to improve the health and well-being of young people. A maximum of 20 secondary schools will be recruited to the pilot SW-SHRN. All students in Years 8 (age 12–13) and 10 (age 14–15) will be invited to complete a health and well-being questionnaire, generating a cohort of approximately 5000 adolescents. School environment questionnaires will also be completed with each school to build a regional picture of existing school health policies and programmes. Each school will be provided with a report summarising data for their students benchmarked against data for all schools in the network. Quantitative analysis will model associations between health risk behaviours and mental health outcomes and a qualitative process evaluation will explore the feasibility and sustainability of the network. This study will create adolescent health data to help provide schools and local authorities with timely and robust information on the health and well-being of their students and help them to identify areas in which public health interventions may be required. SW-SHRN will also help public health professionals focus their resources in the areas most at need.

Published
2022

8. Metal content and kinetic properties of yeast RNA lariat debranching enzyme Dbr1

Author

Nathaniel E. Clark, Adam Katolik, Allison J. Taggart, Luke Buerer, Stephen P. Holloway, Nathaniel Miller, John D. Phillips, Colin P. Farrell, Masad J. Damha, and William G. Fairbrother

Subjects
Metals, Escherichia coli, Humans, RNA, RNA Nucleotidyltransferases, Saccharomyces cerevisiae, Molecular Biology, Introns
Abstract

In eukaryotic cells, intron lariats produced by the spliceosome contain a 2′5′ phosphodiester linkage. The RNA lariat debranching enzyme, Dbr1, is the only enzyme known to hydrolyze this bond. Dbr1 is a member of the metallophosphoesterase (MPE) family of enzymes, and recent X-ray crystal structures and biochemistry data demonstrate that Dbr1 from Entamoeba histolytica uses combinations of Mn2+, Zn2+, and Fe2+ as enzymatic cofactors. Here, we examine the kinetic properties and metal dependence of the Dbr1 homolog from Saccharomyces cerevisiae (yDbr1). Elemental analysis measured stoichiometric quantities of Fe and Zn in yDbr1 purified following heterologous expression E. coli. We analyzed the ability of Fe2+, Zn2+, and Mn2+ to reconstitute activity in metal-free apoenzyme. Purified yDbr1 was highly active, turning over substrate at 5.6 sec−1, and apo-yDbr1 reconstituted with Fe2+ was the most active species, turning over at 9.2 sec−1. We treated human lymphoblastoid cells with the iron-chelator deferoxamine and measured a twofold increase in cellular lariats. These data suggest that Fe is an important biological cofactor for Dbr1 enzymes.

Published
2022

9. Implementation of a New Clinical Testing Tool to Assess Patients During Ictal and Postictal Periods

Author

Sumika Ouchida, Armin Nikpour, Maricar Senturias, Toni E. Pears, and Greg Fairbrother

Subjects
Medical–Surgical Nursing, Epilepsy, Seizures, Endocrine and Autonomic Systems, Humans, Nurses, Electroencephalography, Surgery, Clinical Competence, Neurology (clinical)
Abstract

BACKGROUND: A seizure is a sudden, uncontrolled electrical disturbance of the cortical neurons in the brain, which can cause changes in behavior, movements, feelings, and consciousness. Clinical signs and symptoms before, during, and after a seizure can help to determine the seizure onset. The use of standardized clinical testing tools has been reported as being valuable, although also challenging, by some institutions. This study investigated the effectiveness of implementing a new clinical testing tool designed with an emphasis on simplicity for use during and after seizures. METHODS: A pre-and-post evaluation study was conducted from January 2020 to November 2020 in the epilepsy monitoring unit/neurology unit at a hospital in Sydney, Australia. The primary outcome of interest was the incidence of clinical testing during seizures. The secondary outcome of interest was nurse knowledge about clinical testing during a seizure. This knowledge was measured via testing before and after clinical education sessions. The third outcome of interest was nurse confidence regarding the use of the clinical testing tool. The confidence level was measured via posteducation session follow-up surveying. RESULTS: Forty-seven nursing staff (10 neurophysiology nurse technologists and 37 neurology unit nurses) participated in the education program. Forty-four seizures were evaluated. Clinical testing during ictal and postictal periods was performed by nursing staff 82% of the time during 2020, compared with 67% during the 2018 to 2019 preeducation comparison period. This difference was not statistically significant, but it was clinically relevant (P = .07). In addition, the time from seizure alarm to clinical testing improved significantly from a median of 30.5 seconds in 2018 to 2019 to 14 seconds in 2020 (P.001). CONCLUSION: The tool is easy and convenient for nursing staff to perform clinical examinations accurately during ictal and postictal periods.

Published
2022

10. Crystal structure of the RNA lariat debranching enzyme Dbr1 with hydrolyzed phosphorothioate RNA product

Author

Nathaniel E. Clark, Adam Katolik, Anastasia Welch, Christoph Schorl, Stephen P. Holloway, Jonathan P. Schuermann, P. John Hart, Alexander B. Taylor, Masad J. Damha, and William G. Fairbrother

Subjects
RNA Splicing, Humans, RNA, RNA Nucleotidyltransferases, Biochemistry, Article, Phosphates
Abstract

The RNA lariat debranching enzyme is the sole enzyme responsible for hydrolyzing the 2′–5′ phosphodiester bond in RNA lariats produced by the spliceosome. Here we test the ability of Dbr1 to hydrolyze branched RNAs (bRNAs) which contain a 2′–5′-phosphorothioate linkage, a modification commonly used to resist degradation. We attempted to co-crystallize a phosphorothioate branched RNA (PS-bRNA) with wild-type Entamoeba histolytica Dbr1 (EhDbr1) but observed in-crystal hydrolysis of the phosphorothioate bond. The crystal structure revealed EhDbr1 in a product-bound state, with the hydrolyzed 2′–5′ fragment of the PS-bRNA mimicking the binding mode of the native bRNA substrate. These findings suggest that product inhibition may contribute to the kinetic mechanism of Dbr1. We show that Dbr1 enzymes cleave phosphorothioate linkages at rates ~10,000-fold more slowly than native phosphate linkages. This new product-bound crystal structure offers atomic details which can aid inhibitor design. Dbr1 inhibitors could be therapeutic or investigative compounds for human diseases such as HIV, ALS, cancer, and viral encephalitis.

Published
2022

11. 'There’s a lot of stereotypes going on': A cross-national qualitative analysis of the place of gender in declining youth drinking

Author

Amy Pennay, Jukka Törrönen, Maria Dich Herold, Laura Fenton, Sarah MacLean, Gabriel Caluzzi, Hannah Fairbrother, Vibeke A. Frank, Eva Samuelsson, and John Holmes

Subjects
Male, Masculinity, Cross-national, Adolescent, Alcohol Drinking, Health Policy, Medicine (miscellaneous), Gender, Non-drinking, Underage Drinking, Income, Humans, Female, Young people, Alcohol, Qualitative Research
Abstract

Introduction\ud \ud Significant declines in drinking among young people have been recorded in many high-income countries over the past 20 years. This analysis explored the role of gender - which we interpret as socially constructed and relational - to provide insight into whether and how gender might be implicated in declining youth drinking.\ud \ud \ud \ud Methods\ud \ud Interview data from four independent qualitative studies from Australia, Denmark, Sweden and the UK (n=194; participants aged 15-19 years) were analysed by researchers in each country following agreement about analytical focus. Findings were collated by the lead author in a process of ‘qualitative synthesis’ which involved successive rounds of data synthesis and feedback from the broader research team.\ud \ud \ud \ud Findings\ud \ud Our analysis raised two notable points in relation to the role of gender in declining youth drinking. The first concerned the consistency and vehemence across three of the countries at which drinkers and states of intoxication were pejoratively described in gendered terms (e.g., bitchy, sleazy). The second related to the opportunities non- and light-drinking offered for expressing alternate and desirable configurations of femininities and masculinities.\ud \ud \ud \ud Conclusions\ud \ud We identified an intolerance towards regressive constructions of gender that emphasise weakness for women and strength for men and a valorisation of gendered expressions of maturity through controlled drinking. Though subtle differences in gendered drinking practices between and within countries were observed, our findings offer insight into how young people's enactions of gender are embedded in, and evolve alongside, these large declines in youth drinking.

Published
2022

12. Depression and anxiety during the perinatal period

Author

Allan H. Young, Nichole Fairbrother, Martin M. Antony, Emma Tucker, and Patricia A. Janssen

Subjects
medicine.medical_specialty, Epidemiology, Pregnancy, High-Risk, Population, Comorbidity, Perinatal, Anxiety, Depression, Postpartum, Study Protocol, Clinical Protocols, Pregnancy, Surveys and Questionnaires, medicine, Prevalence, Humans, education, Psychiatry, Depression (differential diagnoses), education.field_of_study, British Columbia, Depression, Incidence (epidemiology), Reproduction, Incidence, AD, medicine.disease, Mental health, Pregnancy Complications, Psychiatry and Mental health, Mood, Mood disorders, Female, medicine.symptom, Psychology, Clinical psychology
Abstract

Background Mood and anxiety and related disorders (AD) account for a significant proportion of mental health conditions, with close to 30 % of the population (28.8 %) suffering from an AD at some time in their life, and over fifteen percent (16.2 %) suffering from a mood disorder. The existing empirical literature leaves a number of important gaps with respect to our understanding of mood, anxiety and stress related difficulties among pregnant and postpartum women. The objective of this research is to address these. Methods Participants were 660 English-speaking pregnant women. Participants for the portion of the research estimating the prevalence/incidence of perinatal mood disorders and AD (N = 347) were recruited proportionally from a geographically defined area. All participants were recruited via prenatal clinic visits at hospitals, physician offices and midwifery clinics, and via community outreach at events and through word of mouth. Recruitment took place between November 9, 2007 and November 12, 2010. Participants were administered questionnaires prenatally at two time points (approximately 24 and 33 weeks gestation) and again at 4–6 weeks’ postpartum and 6-months postpartum. Prevalence/incidence study participants who screened above cut-off on one or more of the 4–6 week mood and anxiety questionnaires were also administered a diagnostic interview for mood disorders and AD at approximately 8–12 weeks postpartum. Discussion This research addresses a number of gaps in our understanding of mood, anxiety and stress among pregnant and postpartum women. Specifically, gaps in our knowledge regarding the prevalence and incidence of (a) AD and mood disorders, and (b) anxiety and stress among women experiencing a medically high-risk pregnancy, interest in stress management training in pregnancy, mental health treatment barriers and access and screening for anxiety among pregnant and postpartum women are addressed. The findings from this series of studies have the potential to improve screening, assessment and treatment of mood and anxiety problems suffered by pregnant and postpartum women.

Published
2022

13. Using systems thinking to understand how the South West - School Health Research Network can improve adolescent health and well-being: A qualitative process evaluation

Author

Emily Widnall, Patricia N. Albers, Lorna Hatch, Georgina Hopkins, Judi Kidger, Frank de Vocht, Eileen Kaner, Esther MF van Sluijs, Hannah Fairbrother, Russell Jago, Rona Campbell, and Apollo - University of Cambridge Repository

Subjects
Mental Health Services, Schools, Systems Analysis, Health (social science), Adolescent, Well-being, Geography, Planning and Development, Adolescent Health, Public Health, Environmental and Occupational Health, Complex adaptive systems, Adolescents, Mental Health, Health, Systems-based intervention, Humans, School Health Services, School health research network
Abstract

Schools offer a valuable setting to promote good health and mental well-being amongst young people. Schools are complex systems and therefore systems interventions are needed to improve pupil health and well-being. This paper presents a qualitative process evaluation of the South West- School Health Research Network, a systems level intervention. The evaluation is based on interviews with school staff, local authorities and wider stakeholders. Given the complexity of England's educational system there is a need to intervene and monitor health at multiple levels and to ensure close partnership working to effectively improve adolescent health through schools.

Published
2023

14. Primary Amine Tethered Small Molecules Promote the Degradation of X-Linked Inhibitor of Apoptosis Protein

Author

Wayne J. Fairbrother, Sayumi Yamazoe, Ingrid E. Wertz, Nicole Blaquiere, Steven T. Staben, Willem den Besten, Domagoj Vucic, Kebing Yu, Melinda M. Mulvihill, Elizabeth Helgason, Erin C. Dueber, Kshitij Verma, Wilson Phung, Tatiana Goncharov, Sumit Prakash, and Anita Izrael-Tomasevic

Subjects
Models, Molecular, chemistry.chemical_classification, DNA ligase, Molecular Structure, biology, X-Linked Inhibitor of Apoptosis Protein, General Chemistry, Crystallography, X-Ray, Inhibitor of apoptosis, Biochemistry, Small molecule, Catalysis, In vitro, XIAP, Cell biology, Small Molecule Libraries, Colloid and Surface Chemistry, chemistry, Ubiquitin, biology.protein, Humans, Inducer, Amines, Function (biology)
Abstract

We hypothesized that the proximity-driven ubiquitylation of E3-interacting small molecules could affect the degradation of E3 ubiquitin ligases. A series of XIAP BIR2 domain-binding small molecules was modified to append a nucleophilic primary amine. This modification transforms XIAP binders into inducers of XIAP degradation. The degradation of XIAP is E1- and proteasome-dependent, dependent on the ligase function of XIAP, and is rescued by subtle modifications of the small molecule that would obviate ubiquitylation. We demonstrate in vitro ubiquitylation of the small molecule that is dependent on its interaction with XIAP. Taken together, these results demonstrate the designed ubiquitylation of an engineered small molecule and a novel approach for the degradation of E3 ubiquitin ligases.

Published
2021

16. Adjustment to an Ostomy: An Integrative Literature Review

Author

Julia Kittscha, Greg Fairbrother, Vida Bliokas, and Val Wilson

Subjects
Advanced and Specialized Nursing, Medical–Surgical Nursing, Ostomy, Humans, Surgical Stomas, Prospective Studies, Qualitative Research
Abstract

This integrative literature review summarizes recent literature relating to patient adjustment to stoma. The search strategy included 5 databases (CINAHL Plus, PsychINFO, Web of Science, Scopus, and MEDLINE); 65 articles meeting criteria were retrieved. Eleven were removed as duplicates, and a further 29 were removed when read in full, yielding 25 elements. Three were randomized controlled trials; 2 were prospective descriptive studies; 15 were cross-sectional descriptive studies; and 5 were qualitative studies. The quality of studies was evaluated using the Mixed Methods Appraisal Tool (MMAT). The calculated mean quality score was 97%, and no studies were excluded on quality grounds. Limited evidence suggests that adjustment occurs over time and provides some insight concerning how rehabilitation leads to resumption of an altered normality. Some evidence suggests that long-term adjustment is associated with demographic and pre- and postoperative factors. A knowledge gap was identified regarding the role of support groups, which in other fields has been shown to positively benefit psychological well-being. This review revealed a paucity of interventional studies seeking to test ways to address adjustment-related problems. Longitudinal studies are recommended as ostomy care nurses work to facilitate adjustment in the person with a stoma over time.

Published
2022

18. Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

Author

Walter Paul Weber, Jane Shaw, Andrea Pusic, Lynda Wyld, Monica Morrow, Tari King, Zoltán Mátrai, Jörg Heil, Florian Fitzal, Shelley Potter, Isabel T. Rubio, Maria-Joao Cardoso, Oreste Davide Gentilini, Viviana Galimberti, Virgilio Sacchini, Emiel J.T. Rutgers, John Benson, Tanir M. Allweis, Martin Haug, Regis R. Paulinelli, Tibor Kovacs, Yves Harder, Bahadir M. Gulluoglu, Eduardo Gonzalez, Andree Faridi, Elisabeth Elder, Peter Dubsky, Jens-Uwe Blohmer, Vesna Bjelic-Radisic, Mitchel Barry, Susanne Dieroff Hay, Kimberly Bowles, James French, Roland Reitsamer, Rupert Koller, Peter Schrenk, Daniela Kauer-Dorner, Jorge Biazus, Fabricio Brenelli, Jaime Letzkus, Ramon Saccilotto, Sarianna Joukainen, Susanna Kauhanen, Ulla Karhunen-Enckell, Juergen Hoffmann, Ulrich Kneser, Thorsten Kühn, Michalis Kontos, Ekaterini Christina Tampaki, Moshe Carmon, Tal Hadar, Giuseppe Catanuto, Carlos A. Garcia-Etienne, Linetta Koppert, Pedro F. Gouveia, Jakob Lagergren, Tor Svensjö, Nadia Maggi, Elisabeth A. Kappos, Fabienne D. Schwab, Liliana Castrezana, Daniel Steffens, Janna Krol, Christoph Tausch, Andreas Günthert, Michael Knauer, Maria C. Katapodi, Susanne Bucher, Nik Hauser, Christian Kurzeder, Rosine Mucklow, Pelagia G. Tsoutsou, Atakan Sezer, Güldeniz Karadeniz Çakmak, Hasan Karanlik, Patricia Fairbrother, Laszlo Romics, Giacomo Montagna, Cicero Urban, Melanie Walker, Silvia C. Formenti, Guenther Gruber, Frank Zimmermann, Daniel Rudolf Zwahlen, Sherko Kuemmel, Mahmoud El-Tamer, Marie Jeanne Vrancken Peeters, Orit Kaidar-Person, Michael Gnant, Philip Poortmans, Jana de Boniface, Weber W. P., Shaw J., Pusic A., Wyld L., Morrow M., King T., Matrai Z., Heil J., Fitzal F., Potter S., et al., Cardoso, Maria-Joao [0000-0002-8137-3700], Apollo - University of Cambridge Repository, HUS Musculoskeletal and Plastic Surgery, Plastiikkakirurgian yksikkö, Tampere University, Department of Surgery, Clinical Medicine, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Surgery

Subjects
Internal Diseases, Mammaplasty, OBSTETRICS & GYNECOLOGY, Sağlık Bilimleri, Doğum ve Jinekoloji, İç Hastalıkları, Clinical Medicine (MED), Breast cancer, KADIN HASTALIKLARI & DOĞUM, Surgery Medicine Sciences, Klinik Tıp (MED), Prospective Studies, Mastectomy, COMPLICATIONS, Implant-based breast reconstruction, Klinik Tıp, Obstetrics and Gynecology, General Medicine, CANCER, Onkoloji, Kadın Hastalıkları ve Doğum, Tıp, Nipples, Cerrahi Tıp Bilimleri, Medicine, Female, ONKOLOJİ, RADIOTHERAPY, 3122 Cancers, Nipple-sparing mastectomy, Breast Neoplasms, Post-mastectomy radiotherapy, SDG 3 - Good Health and Well-being, Health Sciences, Humans, Internal Medicine Sciences, SURGICAL OUTCOMES, TISSUE EXPANDER, Autologous breast reconstruction, INTERNAL MAMMARY, Dahili Tıp Bilimleri, CLINICAL MEDICINE, 3126 Surgery, anesthesiology, intensive care, radiology, ONCOLOGY, TRENDS, IRRADIATION, Surgery, Human medicine, CONSENSUS
Abstract

Funder: Amgen, Funder: Roche, Funder: Universitätsspital Basel, Funder: Merck, Funder: AstraZeneca, Funder: Pfizer, AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.

Published
2022

19. Innovations for the future of breast surgery

Author

Daniel R. Leff, Christopher Holcombe, A Carmichael, C C Kirwan, Deborah Fenlon, A Subramanian, L. Romics, Mark A. Green, E R St John, Shelley Potter, Rachel O'Connell, Ramsey I. Cutress, Fairbrother P, Stuart McIntosh, John R. Benson, and Raghavan Vidya

Subjects
Reconstructive surgery, medicine.medical_specialty, Cost effectiveness, business.industry, Breast surgery, medicine.medical_treatment, Sentinel lymph node, Breast Neoplasms, Mastectomy, Segmental, medicine.disease, Oncoplastic Surgery, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Adjuvant therapy, Breast-conserving surgery, Humans, Medicine, Female, Surgery, 030212 general & internal medicine, business, Intensive care medicine, Forecasting
Abstract

Background Future innovations in science and technology with an impact on multimodal breast cancer management from a surgical perspective are discussed in this narrative review. The work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England. Methods Expert opinion was sought around themes of surgical de-escalation, reduction in treatment morbidities, and improving the accuracy of breast-conserving surgery in terms of margin status. There was emphasis on how the primacy of surgical excision in an era of oncoplastic and reconstructive surgery is increasingly being challenged, with more effective systemic therapies that target residual disease burden, and permit response-adapted approaches to both breast and axillary surgery. Results Technologies for intraoperative margin assessment can potentially half re-excision rates after breast-conserving surgery, and sentinel lymph node biopsy will become a therapeutic procedure for many patients with node-positive disease treated either with surgery or chemotherapy as the primary modality. Genomic profiling of tumours can aid in the selection of patients for neoadjuvant and adjuvant therapies as well as prevention strategies. Molecular subtypes are predictive of response to induction therapies and reductive approaches to surgery in the breast or axilla. Conclusion Treatments are increasingly being tailored and based on improved understanding of tumour biology and relevant biomarkers to determine absolute benefit and permit delivery of cost-effective healthcare. Patient involvement is crucial for breast cancer studies to ensure relevance and outcome measures that are objective, meaningful, and patient-centred.

Published
2021

20. Hotspot exons are common targets of splicing perturbations

Author

David T. Glidden, Jeramiah L. Buerer, Camillo F Saueressig, and William G. Fairbrother

Subjects
0301 basic medicine, RNA Splicing, Science, General Physics and Astronomy, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Exon, 0302 clinical medicine, Humans, splice, Gene, Regulation of gene expression, Multidisciplinary, Binding Sites, Genome, Human, food and beverages, Genetic Variation, RNA-Binding Proteins, General Chemistry, Exons, Gene expression profiling, Alternative Splicing, 030104 developmental biology, Gene Expression Regulation, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), RNA splicing, Mutation, Human genome, RNA Splice Sites
Abstract

High-throughput splicing assays have demonstrated that many exonic variants can disrupt splicing; however, splice-disrupting variants distribute non-uniformly across genes. We propose the existence of exons that are particularly susceptible to splice-disrupting variants, which we refer to as hotspot exons. Hotspot exons are also more susceptible to splicing perturbation through drug treatment and knock-down of RNA-binding proteins. We develop a classifier for exonic splice-disrupting variants and use it to infer hotspot exons. We estimate that 1400 exons in the human genome are hotspots. Using panels of splicing reporters, we demonstrate how the ability of an exon to tolerate a mutation is inversely proportional to the strength of its neighboring splice sites.

Published
2021

21. Variation of microRNA expression in the human placenta driven by population identity and sex of the newborn

Author

Song Guo, Haiyang Hu, Mark Stoneking, Carlos S. Moreno, Shuyun Huang, Xi Jiang, Genevieve L Fairbrother, David A. Hughes, Dingding Han, and Philipp Khaitovich

Subjects
Male, Sequence analysis, Placenta, Population, Biology, QH426-470, 03 medical and health sciences, Sexual dimorphism, 0302 clinical medicine, Pregnancy, microRNA, medicine, Genetics, Humans, RNA, Messenger, Imprinting (psychology), education, Gene, 030304 developmental biology, miRNA, 0303 health sciences, education.field_of_study, Sex Characteristics, Gene Expression Profiling, Populations, Infant, Newborn, Imprinting, Newborn, MicroRNAs, medicine.anatomical_structure, Organ Specificity, Female, DNA microarray, 030217 neurology & neurosurgery, TP248.13-248.65, Research Article, Human, Biotechnology
Abstract

Background Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts. Here, we analyzed microRNA (miRNA) expression in human placental samples derived from 36 individuals representing four genetically distinct human populations: African Americans, European Americans, South Asians, and East Asians. All samples were collected at the same hospital following a unified protocol, thus minimizing potential biases that might influence the results. Results Sequence analysis of the miRNA fraction yielded 938 annotated and 70 novel miRNA transcripts expressed in the placenta. Of them, 82 (9%) of annotated and 11 (16%) of novel miRNAs displayed quantitative expression differences among populations, generally reflecting reported genetic and mRNA-expression-based distances. Several co-expressed miRNA clusters stood out from the rest of the population-associated differences in terms of miRNA evolutionary age, tissue-specificity, and disease-association characteristics. Among three non-environmental influenced demographic parameters, the second largest contributor to miRNA expression variation after population was the sex of the newborn, with 32 miRNAs (3% of detected) exhibiting significant expression differences depending on whether the newborn was male or female. Male-associated miRNAs were evolutionarily younger and correlated inversely with the expression of target mRNA involved in neuron-related functions. In contrast, both male and female-associated miRNAs appeared to mediate different types of hormonal responses. Demographic factors further affected reported imprinted expression of 66 placental miRNAs: the imprinting strength correlated with the mother’s weight, but not height. Conclusions Our results showed that among 12 assessed demographic variables, population affiliation and fetal sex had a substantial influence on miRNA expression variation among human placental samples. The effect of newborn-sex-associated miRNA differences further led to expression inhibition of the target genes clustering in specific functional pathways. By contrast, population-driven miRNA differences might mainly represent neutral changes with minimal functional impacts.

Published
2021

22. Responding to the Challenge of a Pandemic

Author

Danielle Ritz Shala, Nathaniel Alexander, Greg Fairbrother, Aaron Jones, and Suzanne Young

Subjects
Marketing, Pharmacology, Organizational Behavior and Human Resource Management, Medical education, Coronavirus disease 2019 (COVID-19), Strategy and Management, Electronic medical record, COVID-19, Nurses, Pharmaceutical Science, Classroom based, Training (civil), Coronavirus, Blended learning, Drug Discovery, Pandemic, Electronic Health Records, Humans, Learning, Curriculum, Psychology, Pandemics
Published
2021

23. Obesity and Hunger Threaten the Foundations of Child Health

Author

Gerry Fairbrother and Sandra G. Hassink

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Hunger, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Child Health, medicine.disease, Obesity, Article, Child health, Body Mass Index, N/A, Environmental health, Pediatrics, Perinatology and Child Health, medicine, Humans, Child, Psychology
Published
2021

24. Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Author

Jamie J Kirkham, Ellen Copson, Baek Kim, Shelley Potter, Charlotte E. Coles, Nisha Sharma, Elizabeth Camacho, Kieran Horgan, Stuart McIntosh, Daniel R. Leff, Rachel O'Connell, Rajiv V. Dave, Chris Holcombe, Ramsey I. Cutress, Patricia Fairbrother, Christopher W. J. Cartlidge, Ashu Gandhi, Vicky P. Taxiarchi, Alona Courtney, Tim Rattay, Raghavan Vidya, Cliona C. Kirwan, Dave, Rajiv V. [0000-0001-6827-8090], McIntosh, Stuart A. [0000-0002-4123-9611], Potter, Shelley [0000-0002-6977-312X], Copson, Ellen [0000-0001-8994-4056], Apollo - University of Cambridge Repository, Cancer Research UK, Dave, Rajiv V [0000-0001-6827-8090], and McIntosh, Stuart A [0000-0002-4123-9611]

Subjects
Cancer Research, 692/700/784, medicine.medical_treatment, Cohort Studies, 0302 clinical medicine, Breast cancer, Quality of life, Surgical oncology, Pandemic, Epidemiology, 030212 general & internal medicine, 692/700/1538, Aged, 80 and over, Covid19, health policy, Middle Aged, Health care economics, Health policy, Oncology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Female, Breast reconstruction, Life Sciences & Biomedicine, B-MaP-C study collaborative, Cohort study, Adult, medicine.medical_specialty, Breast Neoplasms, Article, 1117 Public Health and Health Services, 692/4028/546, surgical oncology, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, medicine, Humans, 1112 Oncology and Carcinogenesis, 692/700/3934, Oncology & Carcinogenesis, Aged, Science & Technology, business.industry, SARS-CoV-2, COVID-19, health care economics, medicine.disease, Radiation therapy, quality of life, Emergency medicine, 692/4028/67/1347, business
Abstract

Background The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.

Published
2021

25. Do socioeconomic inequities arise during school-based physical activity interventions? An exploratory case study of the GoActive trial

Author

Olivia Alliott, Hannah Fairbrother, Kirsten Corder, Paul Wilkinson, Esther van Sluijs, Alliott, Olivia [0000-0002-1835-6852], and Apollo - University of Cambridge Repository

Subjects
Schools, Adolescent, Socioeconomic Factors, Community child health, EPIDEMIOLOGY, Humans, Health Promotion, General Medicine, PUBLIC HEALTH, Exercise, Body Mass Index
Abstract

Peer reviewed: True, Funder: NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme; Grant(s): IS-BRC-1215-20014, OBJECTIVE: To investigate socioeconomic inequities in the intervention and evaluation process of the GoActive school-based physical activity intervention and demonstrate a novel approach to evaluating intervention-related inequalities. DESIGN: Exploratory post-hoc secondary data analysis of trial data. SETTING: The GoActive trial was run in secondary schools across Cambridgeshire and Essex (UK), between September 2016 and July 2018. PARTICIPANTS: 13-14 years old adolescents (n=2838, 16 schools). METHODS: Socioeconomic inequities across six stages in the intervention and evaluation process were evaluated: (1) provision of and access to resources; (2) intervention uptake; (3) intervention effectiveness (accelerometer-assessed moderate-to-vigorous physical activity (MVPA)); (4) long-term compliance; (5) response in evaluation; and (6) impact on health. Data from self-report and objective measures were analysed by individual-level and school-level socioeconomic position (SEP) using a combination of classical hypothesis tests and multilevel regression modelling. RESULTS: Stage: (1) There was no difference in the provision of physical activity resources by school-level SEP (eg, quality of facilities (0-3), low=2.6 (0.5); high=2.5 (0.4). (2) Students of low-SEP engaged significantly less with the intervention (eg, website access: low=37.2%; middle=45.4%; high=47.0%; p=0.001). (3) There was a positive intervention effect on MVPA in adolescents of low-SEP (3.13 min/day, 95% CI -1.27 to 7.54, but not middle/high (-1.49; 95% CI -6.54 to 3.57). (4) At 10 months post-intervention, this difference increased (low SEP: 4.90; 95% CI 0.09 to 9.70; middle/high SEP: -2.76; 95% CI -6.78 to 1.26). (5) There was greater non-compliance to evaluation measures among adolescents of low-SEP (eg, % accelerometer compliance (low vs high): baseline: 88.4 vs 92.5; post-intervention: 61.6 vs 69.2; follow-up: 54.5 vs 70.2. (6) The intervention effect on body mass index (BMI) z-score was more favourable in adolescents of low-SEP (low SEP: -0.10; 95% CI -0.19 to 0.00; middle/high: 0.03; 95% CI -0.05 to 0.12). CONCLUSIONS: These analyses suggest the GoActive intervention had a more favourable positive effect on MVPA and BMI in adolescents of low-SEP, despite lower intervention engagement. However, differential response to evaluation measures may have biassed these conclusions. We demonstrate a novel way of evaluating inequities within young people's physical activity intervention evaluations. TRIAL REGISTRATION NUMBER: ISRCTN31583496.

Published
2023

26. Clustering of health-related behaviours within children aged 11–16: a systematic review

Author

Hannah Fairbrother, Petra Meier, Penny Curtis, Victoria Whitaker, John Holmes, Jennifer Boyd, and Melissa Oldham

Subjects
medicine.medical_specialty, Youth, Adolescent, State of health, Health Behavior, 03 medical and health sciences, 0302 clinical medicine, Cluster analysis, Health behaviours, Risk Factors, Epidemiology, medicine, Humans, 030212 general & internal medicine, Child, Exercise, Children, Multiple risk factors, 030505 public health, business.industry, Public health, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, Health related, lcsh:RA1-1270, Odds ratio, Latent class model, Diet, Systematic review, Biostatistics, 0305 other medical science, business, Research Article, Clinical psychology
Abstract

Objective We aimed to systematically review and synthesise evidence on the clustering of a broad range of health-related behaviours amongst 11–16 year olds. Method A literature search was conducted in September 2019. Studies were included if they used cluster analysis, latent class analysis, prevalence odds ratios, principal component analysis or factor analysis, and considered at least three health-related behaviours of interest among 11–16 year olds in high-income countries. Health-related behaviours of interest were substance use (alcohol, cigarettes and other drug use) and other behavioural risk indicators (diet, physical activity, gambling and sexual activity). Results The review identified 41 studies, which reported 198 clusters of health-related behaviours of interest. The behaviours of interest reported within clusters were used to define eight behavioural archetypes. Some included studies only explored substance use, while others considered substance use and/or other health-related behaviours. Consequently, three archetypes were comprised by clusters reporting substance use behaviours alone. The archetypes were: (1) Poly-Substance Users, (2) Single Substance Users, (3) Substance Abstainers, (4) Substance Users with No/Low Behavioural Risk Indicators, (5) Substance Abstainers with Behavioural Risk Indicators, (6) Complex Configurations, (7) Overall Unhealthy and (8) Overall Healthy. Conclusion Studies of youth health behavioural clustering typically find both a ‘healthy’ cluster and an ‘unhealthy’ cluster. Unhealthy clusters are often characterised by poly-substance use. Our approach to synthesising cluster analyses may offer a means of navigating the heterogeneity of method, measures and behaviours of interest in this literature.

Published
2021

27. The MARECA (national study of management of breast cancer locoregional recurrence and oncological outcomes) study: National practice questionnaire of United Kingdom multi-disciplinary decision making

Author

Jenna L. Morgan, Vinton Cheng, Peter A. Barry, Ellen Copson, Ramsey I. Cutress, Rajiv Dave, Beatrix Elsberger, Patricia Fairbrother, Sue Hartup, Brian Hogan, Kieran Horgan, Cliona C. Kirwan, Stuart A. McIntosh, Rachel L. O'Connell, Neill Patani, Shelley Potter, Tim Rattay, Lisa Sheehan, Lynda Wyld, and Baek Kim

Subjects
Sentinel Lymph Node Biopsy, Decision Making, Breast Neoplasms, General Medicine, Metastases, Locoregional, Breast cancer, Oncology, SDG 3 - Good Health and Well-being, Recurrence, Lymphatic Metastasis, Surveys and Questionnaires, Axilla, Humans, Lymph Node Excision, Female, Surgery, Neoplasm Recurrence, Local
Abstract

Introduction\ud \ud Evidence based guidelines for the optimal management of breast cancer locoregional recurrence (LRR) are limited, with potential for variation in clinical practice. This national practice questionnaire (NPQ) was designed to establish the current practice of UK breast multidisciplinary teams (MDTs) regarding LRR management.\ud \ud \ud \ud Methods\ud \ud UK breast units were invited to take part in the MARECA study MDT NPQ. Scenario-based questions were used to elicit preference in pre-operative staging investigations, surgical management, and adjuvant therapy.\ud \ud \ud \ud Results\ud \ud 822 MDT members across 42 breast units (out of 144; 29%) participated in the NPQ (February–August 2021). Most units (95%) routinely performed staging CT scan, but bone scan was selectively performed (31%).\ud \ud \ud \ud For patients previously treated with breast conserving surgery (BCS) and radiotherapy, few units (7%) always/usually offered repeat BCS. However, in the absence of radiotherapy, most units (90%) always/usually offered repeat BCS. For patients presenting with isolated local recurrence following previous BCS and SLNB (sentinel lymph node biopsy), most units (95%) advocated repeat SLNB. Where SLNs could not be identified, 86% proceeded to a four-node axillary sampling procedure.\ud \ud \ud \ud For ER positive, HER2 negative, node negative local recurrence, 10% of units always/usually offered chemotherapy. For ER positive, HER2 negative, node positive local recurrence, this recommendation increased to 64%. For triple negative breast cancer local recurrence, 90% of units always/usually offered chemotherapy.\ud \ud \ud \ud Conclusion\ud \ud This survey has highlighted where consistencies and variations exist in the multidisciplinary management of breast cancer LRR. However, further research is required to determine how these management patterns influence patient outcomes, which will further refine optimal treatment pathways.

Published
2022

28. Exploring the potential of a school-based online health and wellbeing screening tool : young people’s perspectives

Author

Nicholas Woodrow, Hannah Fairbrother, Katrina D’Apice, Katie Breheny, Patricia Albers, Clare Mills, Sarah Tebbett, Rona Campbell, and Frank De Vocht

Subjects
child, Schools, Adolescent, schools, screening, adolescent, health, mental health, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, COVID-19, Creativity, School Nursing, HEB, Humans, Mass Screening
Abstract

Despite high levels of need, many young people who experience health issues do not seek, access or receive support. Between May and November 2021, using semi-structured interviews, we explored the perspectives of 51 young people (aged 13–14) from two schools who had taken part in a novel online health and wellbeing screening programme, the Digital Health Contact (DHC). One school delivered the DHC during home-learning due to COVID-19 restrictions, whilst the other delivered it in school when restrictions were lifted. The DHC was seen as a useful approach for identifying health need and providing support, and had high levels of acceptability. Young people appreciated the online format of the DHC screening questionnaire and thought this facilitated more honest responses than a face-to-face approach might generate. Completion at home, compared to school-based completion, was perceived as more private and less time-pressured, which young people thought facilitated more honest and detailed responses. Young people’s understanding of the screening process (including professional service involvement and confidentiality) influenced engagement and responses. Overall, our findings afford important insights around young people’s perspectives of participating in screening programmes, and highlight key considerations for the development and delivery of health screening approaches in (and out of) school.

Published
2022

29. Are changes in attitudes towards school associated with declining youth drinking? A multi-level analysis of 37 countries

Author

Abigail K Stevely, Rakhi Vashishtha, Hannah Fairbrother, Laura Fenton, Madeleine Henney, Michael Livingston, and John Holmes

Subjects
Adolescent, Alcohol Drinking, Attitude, Adolescent Behavior, Public Health, Environmental and Occupational Health, 111799 Public Health and Health Services not elsewhere classified, Humans, Female, Underage Drinking, FOS: Health sciences, Child, Alcoholic Intoxication
Abstract

BackgroundChanges in adolescents’ attitudes towards school are a potential explanation for recent declines in young people’s alcohol consumption. However, this has not been tested using multi-national survey data, which would permit stronger causal inferences by ruling out other country-specific explanations. This study, therefore, uses an international survey of schoolchildren to examine the associations between changing attitudes towards school and adolescent alcohol consumption.MethodsWe used data from 247 325 15-year-olds across 37 countries participating in four waves of the Health Behaviour in School-aged Children study (2001/02–2013/14). Attitudes towards school were assessed using two measures—self-reported pressure from schoolwork and whether respondents like school. Outcome measures were weekly alcohol consumption and having been drunk twice in one’s lifetime. We used whole population and gender-specific hierarchical linear probability models to assess the relationship between attitudes and alcohol outcomes within countries over time.ResultsCountry-level changes over time in liking school were not associated with changes in alcohol consumption. However, a 10% increase in feeling pressured by schoolwork was associated with a 1.8% decline in drunkenness [95% confidence interval (CI): −3.2% to −0.3%] and weakly associated with a 1.7% decline in weekly drinking (95% CI: −3.6% to 0.2%). Among girls only, increases in feeling pressured by schoolwork were associated with a 2.1% decline in weekly drinking (95% CI: −3.7% to −0.6%) and a 2.4% decline in drunkenness (95% CI: −3.8% to −1.1%).ConclusionChanges in attitudes towards school may have played a minor role in the decline in alcohol consumption among adolescent girls only.

Published
2022

30. A Prospective Randomized Controlled Trial: Alternative Approach to EEG Application to Reduce Electrode-induced Skin Injury among Ambulatory EEG Patients

Author

Sumika Ouchida, Armin Nikpour, and Greg Fairbrother

Subjects
Medical Laboratory Technology, Humans, Monitoring, Ambulatory, Electroencephalography, Neurology (clinical), Prospective Studies, Electrodes
Abstract

Ambulatory electroencephalography (AEEG) is a technique of continuous EEG recording of patients in their natural setting, outside the controlled environment of the hospital. Electrode-induced skin injury is a common complication of prolonged EEG monitoring. This randomized study aimed to investigate the performance of two methods of electrode application in reducing electrode-induced skin injury among patients undergoing 4-day AEEG monitoring. A randomized interventional study was conducted from November 2020 to May 2021 in the Neurosciences Ambulatory Care Unit at a metropolitan hospital in Sydney, Australia. We enrolled patients into two groups: i) Group 1 (standard protocol group) received Ten20 Conductive Paste

Published
2022

31. Medical Student Perspectives on the Ethics of Pelvic Exams Under Anesthesia: A Multi-Institutional Study✰

Author

Karampreet Kaur, Sanjana Salwi, Kelsey McNew, Nimisha Kumar, Hannah Millimet, Niharika Ravichandran, Karla Tytus, Angela Y. Zhang, Angelica Garrett Wood, Barry Grimm, and Erin L. Fairbrother

Subjects
Obstetrics, Students, Medical, Pregnancy, Gynecology, Clinical Clerkship, Humans, Surgery, Female, Anesthesia, Ethics, Medical, Gynecological Examination, Education
Abstract

Pelvic examinations under anesthesia (EUAs) are routine components of gynecologic surgery and often used to educate students about female pelvic anatomy. This multi-institutional survey study aims to describe students' experiences with conducting educational pelvic EUAs and their attitudes around the ethics of informed consent for these exams.An anonymous survey of Likert and open-text response questions about institutions' practices around educational pelvic EUAs was sent to medical students.Medical schools included Vanderbilt University School of Medicine, Indiana University School of Medicine, Emory University School of Medicine, University of New Mexico School of Medicine, Meharry Medical College, and Warren Alpert Medical School of Brown University.A total 305 medical students who had completed their obstetrics and gynecology (OB/GYN) clerkship between June 2019 and March 2020 filled out the survey (33% response rate).Overall, 84% of students performed at least 1 pelvic EUA during their clerkship. Of the 42% (142) of students that observed patient informed consent processes most or every time, 67% reported they never or rarely witnessed an explicit explanation that a medical student may perform a pelvic EUA. Analysis of open-text responses found that students wanted to uphold patient autonomy but felt they did not have the personal autonomy to object to performing pelvic EUAs that they believed were unconsented. They faced significant emotional distress when consent processes were at odds with their personal ethos and professional ethical norms. Students favored more standardized and explicit patient consent processes for educational pelvic EUAs.While students regularly perform pelvic EUAs, their involvement is inconsistently disclosed to patients, causing significant distress to students and risking erosion of students' attitudes about upholding patient autonomy and informed consent. Medical institutions must develop consistent, ethical, and patient-centered processes for trainee disclosure around pelvic EUAs.

Published
2022

33. Assessing predictions of the impact of variants on splicing in CAGI5

Author

Rita Casadio, Jun Cheng, Ron Unger, Žiga Avsec, Ken Chen, Noa E. Cohen, Julien Gagneur, Chiao-Feng Lin, Robert Y. Wang, William G. Fairbrother, Yuedong Yang, Tamar Holzer, Thi Yen Duong Nguyen, Pier Luigi Martelli, Tzila Fenesh, Liran Carmel, Stephen M. Mount, Valer Gotea, Castrense Savojardo, Muhammed Hasan Çelik, Huiying Zhao, Tatsuhiko Naito, Mount S.M., Avsec Z., Carmel L., Casadio R., Celik M.H., Chen K., Cheng J., Cohen N.E., Fairbrother W.G., Fenesh T., Gagneur J., Gotea V., Holzer T., Lin C.-F., Martelli P.L., Naito T., Nguyen T.Y.D., Savojardo C., Unger R., Wang R., Yang Y., and Zhao H.

Subjects
Sequencing data, Computational biology, Biology, Genome, Article, splicing, 03 medical and health sciences, Exon, Sequence Homology, Nucleic Acid, Genetics, CAGI experiment, Animals, Humans, Sequence variation, Genetics (clinical), 030304 developmental biology, Sequence (medicine), 0303 health sciences, Models, Genetic, variant interpretation, 030305 genetics & heredity, Computational Biology, Proteins, Congresses as Topic, Precision medicine, Alternative Splicing, machine learning, Mutation, RNA splicing, Critical assessment, Genetic Fitness
Abstract

Precision medicine and sequence-based clinical diagnostics seek to predict disease risk or to identify causative variants from sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. In the past, few CAGI challenges have addressed the impact of sequence variants on splicing. In CAGI5, two challenges (Vex-seq and MaPSY) involved prediction of the effect of variants, primarily single-nucleotide changes, on splicing. Although there are significant differences between these two challenges, both involved prediction of results from high-throughput exon inclusion assays. Here, we discuss the methods used to predict the impact of these variants on splicing, their performance, strengths, and weaknesses, and prospects for predicting the impact of sequence variation on splicing and disease phenotypes.

Published
2019

34. Trends in the psychosocial characteristics of 11–15‐year‐olds who still drink, smoke, take drugs and engage in poly‐substance use in England

Author

Penny Curtis, Victoria Whitaker, Petra Meier, Melissa Oldham, Hannah Fairbrother, Sarah Callinan, John Holmes, and Michael Livingston

Subjects
Drug, Health (social science), Adolescent, Alcohol Drinking, Substance-Related Disorders, media_common.quotation_subject, 030508 substance abuse, Medicine (miscellaneous), 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Smoke, Environmental health, Prevalence, Humans, Medicine, 030212 general & internal medicine, Poisson regression, Child, Socioeconomic status, media_common, biology, Illicit Drugs, business.industry, biology.organism_classification, Cross-Sectional Studies, symbols, Cannabis, Truancy, Substance use, 0305 other medical science, business, Psychosocial
Abstract

INTRODUCTION AND AIMS: Youth substance use is declining in many high-income countries. As adolescent substance use becomes less common, it may concentrate in higher-risk groups. This paper aims to examine how the psychosocial characteristics of young substance users in England have changed over time. DESIGN AND METHODS: Annual cross-sectional data from the 2001-2014 Smoking, Drinking and Drug Use Among Young People in England survey are analysed (n = 112 792, age: 11-15). Logistic and Poisson regression analyses are used to test whether the sex, socioeconomic status (SES) and prevalence of truancy and exclusion from school of those who drink alcohol, smoke cigarettes, take cannabis, take other drugs and engage in poly-substance use changed across the study period. RESULTS: Use of all substances decreased and there were shifts in the psychosocial characteristics of young smokers, illicit drug users and poly-substance users. The proportion of current smokers and ever-users of cannabis of low SES and who had been excluded increased significantly between 2001/2003-2014. The proportion of last month drug users who had been excluded from school also increased significantly and there were increases in the proportion of polysubstance-users who had truanted and been excluded. The proportion of low SES alcohol users who had been excluded also increased significantly, but this change was very small. There was no evidence of substance use becoming more or less concentrated in one gender. DISCUSSION AND CONCLUSIONS: There is some evidence that smoking, illicit drug use and poly-substance use are becoming more concentrated in potentially at risk populations. There is limited evidence of concentration amongst young drinkers.

Published
2020

35. Mutational bias and the protein code shape the evolution of splicing enhancers

Author

Luke Buerer, William G. Fairbrother, Kamil J. Cygan, Christy L. Rhine, Stephen Rong, and Jing Wang

Subjects
0301 basic medicine, RNA splicing, Science, General Physics and Astronomy, Genomics, Computational biology, Biology, Genome, General Biochemistry, Genetics and Molecular Biology, Article, Evolutionary genetics, Evolution, Molecular, 03 medical and health sciences, Negative selection, Exon, 0302 clinical medicine, Molecular evolution, Humans, Computer Simulation, Enhancer, lcsh:Science, Multidisciplinary, Models, Genetic, Genome, Human, Intron, General Chemistry, Exons, Introns, High-Throughput Screening Assays, 030104 developmental biology, Enhancer Elements, Genetic, Mutation, lcsh:Q, 030217 neurology & neurosurgery
Abstract

Exonic splicing enhancers (ESEs) are enriched in exons relative to introns and bind splicing activators. This study considers a fundamental question of co-evolution: How did ESE motifs become enriched in exons prior to the evolution of ESE recognition? We hypothesize that the high exon to intron motif ratios necessary for ESE function were created by mutational bias coupled with purifying selection on the protein code. These two forces retain certain coding motifs in exons while passively depleting them from introns. Through the use of simulations, genomic analyses, and high throughput splicing assays, we confirm the key predictions of this hypothesis, including an overlap between protein and splicing information in ESEs. We discuss the implications of mutational bias as an evolutionary driver in other cis-regulatory systems., Splicing is regulated by cis-acting elements in pre-mRNAs such as exonic or intronic splicing enhancers and silencers. Here the authors show that exonic splicing enhancers are enriched in exons compared to introns due to mutational bias coupled with purifying selection on the protein code.

Published
2020

36. Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

Author

Chappell, E., Riordan, A., Jourdain, G., Soriano-Arandes, A., Ene, L., Scherpbier, H., Warszawski, J., Collins, I., Smit, C., Marques, L., Klein, N., Guillén, S., Judd, A., Thorne, C., Goodall, R., Königs, C., Spoulou, V., Prata, F., Goetghebuer, T., Chiappini, E., Galli, L., Naver, L., Giaquinto, C., Gibb, D., Marczynska, M., Okhonskaia, L., Klimkait, T., Lallemant, M., Ngo-Giang-Huong, N., Kiseleva, G., Malyuta, R., Volokha, A., Hainaut, M., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait Si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Levine, M., Bicëtre, L., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., Lalande, M., Schultze-Strasser, S., Baumann, U., Niehues, T., Neubert, J., Kobbe, R., Berlin, C., Feiterna-Sperling, C., Buchholz, B., Notheis, G., de Martino, M., Angelo Tovo, P., Patrizia, O., Larovere, D., Ruggeri, M., Faldella, G., Baldi, F., Badolato, R., Montagnani, C., Venturini, E., Lisi, C., Di Biagio, A., Taramasso, L., Giacomet, V., Erba, P., Esposito, S., Lipreri, R., Salvini, F., Tagliabue, C., Cellini, M., Bruzzese, E., Lo Vecchio, A., Rampon, O., Donà, D., Romano, A., Dodi, I., Maccabruni, A., Consolini, R., Bernardi, S., Tchidjou Kuekou, H., Genovese, O., Olmeo, P., Cristiano, L., Mazza, A., Gabiano, C., Garazzino, S., Pellegatta, A., Pajkrt, D., Weijsenfeld, A., de Boer CG, Jurriaans, S., Back, N., Zaaijer, H., Berkhout, B., Cornelissen, M., Schinkel, C., Wolthers, K., Fraaij, P., van Rossum AMC, van der Knaap LC, Visser, E., Koopmans, M., van Kampen JJA, Pas, S., Henriet, S., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F., Schölvinck, E., de Groot-de Jonge, H., Niesters, H., van Leer-Buter CC, Knoester, M., Bont, L., Geelen, S., Wolfs, T., Nauta, N., Ang, C., van Houdt, R., Pettersson, A., Vandenbroucke-Grauls, C., Reiss, P., Bezemer, D., van Sighem AI, Wit, F., Boender, T., Zaheri, S., Hillebregt, M., de Jong, A., Bergsma, D., Grivell, S., Jansen, A., Raethke, M., Meijering, R., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Popielska, J., Pokorska-Śpiewak, M., Ołdakowska, A., Zawadka, K., Coupland, U., DorobaLaura Marques, M., Teixeira, C., Fernandes, A., Voronin, E., Miloenko, M., Labutina, S., Tomás Ramos, J., Prieto, L., Luisa Navarro, M., Saavedra, J., Santos, M., Angeles Muñoz, M., Ruiz, B., Mc Phee CF, de Ory SJ, Alvarez, S., Ángel Roa, M., Beceiro, J., Martínez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Gómez Sirvent, J., Garzón, M., Román, V., Montesdeoca, A., Mateo, M., José Muñoz, M., Angulo, R., Neth, O., Falcón, L., Terol, P., Luis Santos, J., Moreno, D., Lendínez, F., Grande, A., José Romero, F., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Antonio Couceiro, J., Pérez, A., Isabel Piqueras, A., Bretón, R., Segarra, I., Gavilán, C., Jareño, E., Montesinos, E., Dapena, M., Álvarez, C., Gloria Andrés, A., Marugán, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., de Miguel, E., Aebi-Popp, K., Asner, S., Aubert, V., Battegay, M., Baumann, M., Bernasconi, E., Böni, J., Brazzola, P., Bucher, H., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C., Grawe, C., Günthard, H., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., de Tejada BM, Metzner, K., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Polli, C., Posfay-Barbe, K., Rauch, A., Rudin, C., Schmid, P., Scherrer, A., Speck, R., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C., Yerly, S., Techakunakorn, P., Hansudewechakul, R., Kham, C., Wanchaitanawong, V., Theansavettrakul, S., Sai, M., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Phuket, V., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Bailey, H., Bamford, A., Butler, K., Doerholt, K., Doherty, C., Foster, C., Francis, K., Harrison, I., Kenny, J., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Peters, H., Prime, K., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Jeannie Collins, I., Cook, C., Crichton, S., Dobson, D., Fairbrother, K., M Gibb D, Harper, L., Le Prevost, M., Van Looy, N., Walsh, A., Thrasyvoulou, L., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Sloper, K., Fidler, K., Hague, R., Price, V., Clapson, M., Flynn, J., Cardoso, A., Abou-Rayyah, M., Gurtin, D., Yeadon, S., Segal, S., Ball, C., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Clough, S., Anguvaa, L., Conway, S., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, B., Pope, S., Cliffe, L., Smyth, A., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rogahn, D., Clarke, L., Jones, L., Offerman, B., Greenberg, M., Benson, C., Ibberson, L., Faust, S., Hancock, J., Sharland, M., Lyall, H., Monrose, C., Seery, P., Menson, E., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Critchton, S., Duff, C., Gomezpena, D., Lundin, R., Mangiarini, L., Nardone, A., Posfay Barbe, Klara, Universidad de Alcalá - University of Alcalá (UAH), Department of Sciences for Woman and Child's Health, Università degli Studi di Firenze = University of Florence (UniFI), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University-Chiang Mai University (CMU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Saint-Denis [Ile-de-France], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universitätsklinikum Frankfurt, Infectious Diseases, San Martino Hospital, Università degli studi di Genova = University of Genoa (UniGe), Department of Maternal and Pediatric Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Maternal-Infantile Department, Unit of Paediatrics and Oncohematology, University Hospital of Parma, Department of Infectious Diseases, IRCCS S. Matteo, Department of Paediatrics, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Dipartimento di Ingegneria [Benevento], Università degli Studi del Sannio, University of Twente, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Infectious Diseases and Perinatal Screening, Center for Infectious Disease Control, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Synthèse, Structure et Propriétés de Matériaux Fonctionnels (STEP), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Stichting HIV Monitoring, Universidade Federal do Ceará = Federal University of Ceará (UFC), Departamento de Química Orgánica, Universidade de Vigo, Polytechnical University of Valencia, Fac Biol, Dept Genet, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Service des maladies infectieuses, Hôpitaux Universitaires de Genève (HUG), University of Basel (Unibas), Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), University Heart Centre Freiburg - Bad Krozingen, Prapokklao Hospital [Chanthaburi, Thailand], Nakornping Hospital [Chiang Mai, Thailand], Samutsakhon Hospital [Samutsakhon, Thailand], Kalasin Hospital [Kalasin, Thailand], Sanpatong Hospital [Chiang Mai, Thailand], Chiang Mai University (CMU), Microbiology Department, St. Jame's Hospital, University of Edinburgh, Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, European Synchrotron Radiation Facility (ESRF), Centre for Ecology and Hydrology [Bangor] (CEH), Natural Environment Research Council (NERC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), University of London [London], London South Bank University (LSBU), Dipartimento di Pediatria, Azienda Ospedaliera di Padova, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord, Florence University, Harvard University [Cambridge]-Chiang Mai University (CMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Genoa (UNIGE), Catholic University of Rome, University of Twente [Netherlands], Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of the Basque Country [Bizkaia] (UPV/EHU), Université Nice Sophia Antipolis (... - 2019) (UNS), Pediatrics, Virology, Chappell, Elizabeth, Riordan, Andrew, Jourdain, Gonzague, Soriano-Arandes, Antoni, Ene, Luminita, J Scherpbier, Henriette, Warszawski, Josiane, J Collins, Intira, Smit, Colette, Marques, Laura, Klein, Nigel, Guillén, Sara, Judd, Ali, Thorne, Claire, Goodall, Ruth, Königs, Christoph, Spoulou, Vana, Prata, Filipa, Goetghebuer, Tessa, Chiappini, Elena, Galli, Luisa, Naver, Lar, Giaquinto, Carlo, M Gibb, Diana, Marczynska, Magdalena, Okhonskaia, Liubov, Klimkait, Thoma, Lallemant, Marc, Ngo-Giang-Huong, Nicole, Kiseleva, Galyna, Malyuta, Ruslan, Volokha, Alla, Hainaut, Marc, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Levine, Martine, Kremlin Bicëtre, Le, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, Lalande, Muriel, Schultze-Strasser, Stephan, Baumann, U, Niehues, T, Neubert, J, Kobbe, R, Berlin, Charite, Feiterna-Sperling, C, Königs, C, Buchholz, B, Notheis, G, de Martino, Maurizio, Angelo Tovo, Pier, Patrizia, Osimani, Larovere, Domenico, Ruggeri, Maurizio, Faldella, Giacomo, Baldi, Francesco, Badolato, Raffaele, Montagnani, Carlotta, Venturini, Elisabetta, Lisi, Catiuscia, Di Biagio, Antonio, Taramasso, Lucia, Giacomet, Vania, Erba, Paola, Esposito, Susanna, Lipreri, Rita, Salvini, Filippo, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, LO VECCHIO, Andrea, Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, Infectious diseases, and Global Health

Subjects
0301 basic medicine, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections, Rate ratio, Cohort Studies, 0302 clinical medicine, Pregnancy, Antiretroviral Therapy, Highly Active, Prevalence, 030212 general & internal medicine, Child, poor immune response, ddc:618, Immunosuppression, Viral Load, Hepatitis B, Thailand, 3. Good health, Europe, Thailand/epidemiology, Infectious Diseases, Cohort, Coinfection, Female, Cohort study, Adult, Microbiology (medical), viral suppression, medicine.medical_specialty, Adolescent, Anti-HIV Agents, antiretroviral therapy, 030106 microbiology, Europe/epidemiology, 03 medical and health sciences, children, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, HIV, Aged, Settore MED/38 - Pediatria Generale e Specialistica, business.industry, Immunity, medicine.disease, HIV Infections/drug therapy/epidemiology, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Anti-HIV Agents/therapeutic use, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.

Published
2020

37. A highly virulent variant of HIV-1 circulating in the Netherlands

Author

Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, Gall, Astrid, Hall, Matthew, Golubchik, Tanya, Bakker, Margreet, Ong, Swee Hoe, Zhao, Lele, Bonsall, David, de Cesare, Mariateresa, MacIntyre-Cockett, George, Abeler-Dörner, Lucie, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F, Kivelä, Pia, Kouyos, Roger D, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B Martinez, Marzolini, C, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Weber, R, Yerly, S, van der Valk, M, Geerlings, S E, Goorhuis, A, Hovius, J W, Lempkes, B, Nellen, F J B, van der Poll, T, Prins, J M, Reiss, P, van Vugt, M, Wiersinga, W J, Wit, F W M N, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A M H, Pijnappel, F J J, Smalhout, S Y, Weijsenfeld, A M, Jurriaans, S, Back, N K T, Zaaijer, H L, Berkhout, B, Cornelissen, M T E, Schinkel, C J, Wolthers, K C, Peters, E J G, van Agtmael, M A, Autar, R S, Bomers, M, Sigaloff, K C E, Heitmuller, M, Laan, L M, Ang, C W, van Houdt, R, Jonges, M, Kuijpers, T W, Pajkrt, D, Scherpbier, H J, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Buiting, A, Reuwer, A, Veenemans, J, Wintermans, B, Pronk, M J H, Ammerlaan, H S M, van den Bersselaar, D N J, de Munnik, E S, Deiman, B, Jansz, A R, Scharnhorst, V, Tjhie, J, Wegdam, M C A, van Eeden, A, Nellen, J, Brokking, W, Elsenburg, L J M, Nobel, H, van Kasteren, M E E, Berrevoets, M A H, Brouwer, A E, Adams, A, van Erve, R, de Kruijf-van de Wiel, B A F M, Keelan-Phaf, S, van der Ven, B, Buiting, A G M, Murck, J L, de Vries-Sluijs, T E M S, Bax, H I, van Gorp, E C M, de Jong-Peltenburg, N C, de Mendonç A Melo, M, van Nood, E, Nouwen, J L, Rijnders, B J A, Rokx, C, Schurink, C A M, Slobbe, L, Verbon, A, Bassant, N, van Beek, J E A, Vriesde, M, van Zonneveld, L M, de Groot, J, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Fraaij, P L A, van Rossum, A M C, Vermont, C L, van der Knaap, L C, Visser, E, Branger, J, Douma, R A, Cents-Bosma, A S, Duijf-van de Ven, C J H M, Schippers, E F, van Nieuwkoop, C, van Ijperen, J M, Geilings, J, van der Hut, G, van Burgel, N D, Leyten, E M S, Gelinck, L B S, Mollema, F, Davids-Veldhuis, S, Tearno, C, Wildenbeest, G S, Heikens, E, Groeneveld, P H P, Bouwhuis, J W, Lammers, A J J, Kraan, S, van Hulzen, A G W, Kruiper, M S M, van der Bliek, G L, Bor, P C J, Debast, S B, Wagenvoort, G H J, Kroon, F P, de Boer, M G J, Jolink, H, Lambregts, M M C, Roukens, A H E, Scheper, H, Dorama, W, van Holten, N, Claas, E C J, Wessels, E, den Hollander, J G, El Moussaoui, R, Pogany, K, Smit, J V, Struik-Kalkman, D, van Niekerk, T, Pontesilli, O, Lowe, S H, Oude Lashof, A M L, Posthouwer, D, van Wolfswinkel, M E, Ackens, R P, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I H M, Havenith, T R A, van Vonderen, M G A, Kampschreur, L M, Faber, S, Steeman-Bouma, R, Al Moujahid, A, Kootstra, G J, Delsing, C E, van der Burg-van de Plas, M, Scheiberlich, L, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F A, Cohen Stuart, J W T, Jansen, E R, Hoogewerf, M, Rozemeijer, W, van der Reijden, W A, Sinnige, J C, Brinkman, K, van den Berk, G E L, Blok, W L, Lettinga, K D, de Regt, M, Schouten, W E M, Stalenhoef, J E, Veenstra, J, Vrouenraets, S M E, Blaauw, H, Geerders, G F, Kleene, M J, Kok, M, Knapen, M, van der Meché, I B, Mulder-Seeleman, E, Toonen, A J M, Wijnands, S, Wttewaal, E, Kwa, D, van Crevel, R, van Aerde, K, Dofferhoff, A S M, Henriet, S S V, Ter Hofstede, H J M, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K J T, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F F, Burger, D, Gisolf, E H, Hassing, R J, Claassen, M, Ter Beest, G, van Bentum, P H M, Langebeek, N, Tiemessen, R, Swanink, C M A, van Lelyveld, S F L, Soetekouw, R, van der Prijt, L M M, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B L, Veenendaal, D, Verhagen, D W M, Lauw, F N, van Broekhuizen, M C, van Wijk, M, Bierman, W F W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Postma, D F, Schölvinck, E H, Stienstra, Y, Verhage, A R, Wouthuyzen-Bakker, M, Boonstra, A, de Groot-de Jonge, H, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Knoester, M, Hoepelman, A I M, Arends, J E, Barth, R E, Bruns, A H W, Ellerbroek, P M, Mudrikova, T, Oosterheert, J J, Schadd, E M, van Welzen, B J, Aarsman, K, Griffioen-van Santen, B M G, de Kroon, I, van Berkel, M, van Rooijen, C S A M, Schuurman, R, Verduyn-Lunel, F, Wensing, A M J, Bont, L J, Geelen, S P M, Loeffen, Y G T, Wolfs, T F W, Nauta, N, Rooijakkers, E O W, Holtsema, H, Voigt, R, van de Wetering, D, Alberto, A, van der Meer, I, Rosingh, A, Halaby, T, Zaheri, S, Boyd, A C, Bezemer, D O, van Sighem, A I, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Brétin, N, Djoechro, E, Groters, M, Kruijne, E, Lelivelt, K J, Lodewijk, C, Lucas, E, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnörr, P, Scheigrond, A, Tuijn, E, Veenenberg, L, Visser, K M, Witte, E C, Van Frankenhuijsen, Maartje, Allegre, Thierry, Makhloufi, Djamila, Livrozet, Jean-Michel, Chiarello, Pierre, Godinot, Mathieu, Brunel-Dalmas, Florence, Gibert, Sylvie, Trepo, Christian, Peyramond, Dominique, Miailhes, Patrick, Koffi, Joseph, Thoirain, Valérie, Brochier, Corinne, Baudry, Thomas, Pailhes, Sylvie, Lafeuillade, Alain, Philip, Gisèle, Hittinger, Gilles, Assi, Assi, Lambry, Véronique, Rosenthal, Eric, Naqvi, Alissa, Dunais, Brigitte, Cua, Eric, Pradier, Christian, Durant, Jacques, Joulie, Aline, Quinsat, Denis, Tempesta, Serge, Ravaux, Isabelle, Martin, Isabelle Poizot, Faucher, Olivia, Cloarec, Nicolas, Champagne, Hélène, Pichancourt, Gilles, Morlat, Philippe, Pistone, Thierry, Bonnet, Fabrice, Mercie, Patrick, Faure, Isabelle, Hessamfar, Mojgan, Malvy, Denis, Lacoste, Denis, Pertusa, Marie-Carmen, Vandenhende, Marie-Anne, Bernard, Noëlle, Paccalin, François, Martell, Cédric, Roger-Schmelz, Julien, Receveur, Marie-Catherine, Duffau, Pierre, Dondia, Denis, Ribeiro, Emmanuel, Caltado, Sabrina, Neau, Didier, Dupont, Michel, Dutronc, Hervé, Dauchy, Frédéric, Cazanave, Charles, Vareil, Marc-Olivier, Wirth, Gaétane, Le Puil, Séverine, Pellegrin, Jean-Luc, Raymond, Isabelle, Viallard, Jean-François, Chaigne de Lalande, Severin, Garipuy, Daniel, Delobel, Pierre, Obadia, Martine, Cuzin, Lise, Alvarez, Muriel, Biezunski, Noemie, Porte, Lydie, Massip, Patrice, Debard, Alexa, Balsarin, Florence, Lagarrigue, Myriam, Prevoteau du Clary, François, Aquilina, Christian, Reynes, Jacques, Baillat, Vincent, Merle, Corinne, Lemoing, Vincent, Atoui, Nadine, Makinson, Alain, Jacquet, Jean Marc, Psomas, Christina, Tramoni, Christine, Aumaitre, Hugues, Saada, Mathieu, Medus, Marie, Malet, Martine, Eden, Aurélia, Neuville, Ségolène, Ferreyra, Milagros, Sotto, Albert, Barbuat, Claudine, Rouanet, Isabelle, Leureillard, Didier, Mauboussin, Jean-Marc, Lechiche, Catherine, Donsesco, Régine, Cabie, André, Abel, Sylvie, Pierre-Francois, Sandrine, Batala, Anne-Sophie, Cerland, Christophe, Rangom, Camille, Theresine, Nadine, Hoen, Bruno, Lamaury, Isabelle, Fabre, Isabelle, Schepers, Kinda, Curlier, Elodie, Ouissa, Rachida, Gaud, Catherine, Ricaud, Carole, Rodet, Roland, Wartel, Guillaume, Sautron, Carmele, Beck-Wirth, Geneviève, Michel, Catherine, Beck, Charles, Halna, Jean-Michel, Kowalczyk, Jakub, Benomar, Meryem, Drobacheff-Thiebaut, Christine, Chirouze, Catherine, Faucher, Jean-François, Parcelier, François, Foltzer, Adeline, Haffner-Mauvais, Cécile, Hustache Mathieu, Mathieu, Proust, Aurélie, Piroth, Lionel, Chavanet, Pascal, Duong, Michel, Buisson, Marielle, Waldner, Anne, Mahy, Sophie, Gohier, Sandrine, Croisier, Delphine, May, Thierry, Delestan, Mikael, Andre, Marie, Zadeh, Mahsa Mohseni, Martinot, Martin, Rosolen, Béatrice, Pachart, Anne, Martha, Benoît, Jeunet, Noëlle, Rey, David, Cheneau, Christine, Partisani, Maria, Priester, Michèle, Bernard-Henry, Claudine, Batard, Marie-Laure, Fischer, Patricia, Berger, Jean-Luc, Kmiec, Isabelle, Robineau, Olivier, Huleux, Thomas, Ajana, Faïza, Alcaraz, Isabelle, Allienne, Christophe, Baclet, Véronique, Meybeck, Agnès, Valette, Michel, Viget, Nathalie, Aissi, Emmanuelle, Biekre, Raphael, Cornavin, Pauline, Merrien, Dominique, Seghezzi, Jean-Christophe, Machado, Moise, Diab, Georges, Raffi, François, Bonnet, Bénédicte, Allavena, Clotilde, Grossi, Olivier, Reliquet, Véronique, Billaud, Eric, Brunet, Cecile, Bouchez, Sabelline, Morineau-Le Houssine, Pascale, Sauser, Fabienne, Boutoille, David, Besnier, Michel, Hue, Hervé, Hall, Nolwenn, Brosseau, Delphine, Souala, Faouzi, Michelet, Christian, Tattevin, Pierre, Arvieux, Cédric, Revest, Matthieu, Leroy, Helene, Chapplain, Jean-Marc, Dupont, Matthieu, Fily, Fabien, Patra-Delo, Solène, Lefeuvre, Céline, Bernard, Louis, Bastides, Frédéric, Nau, Pascale, Verdon, Renaud, de la Blanchardiere, Arnaud, Martin, Anne, Feret, Philippe, Geffray, Loïk, Daniel, Corinne, Rohan, Jennifer, Fialaire, Pascale, Chennebault, Jean Marie, Rabier, Valérie, Abgueguen, Pierre, Rehaiem, Sami, Luycx, Odile, Niault, Mathilde, Moreau, Philippe, Poinsignon, Yves, Goussef, Marie, Mouton-Rioux, Virginie, Houlbert, Dominique, Alvarez-Huve, Sandrine, Barbe, Frédérique, Haret, Sophie, Perre, Philippe, Leantez-Nainville, Sophie, Esnault, Jean-Luc, Guimard, Thomas, Suaud, Isabelle, Girard, Jean-Jacques, Simonet, Véronique, Debab, Yasmine, Schmit, Jean-Luc, Jacomet, Christine, Weinberck, Pierre, Genet, Claire, Pinet, Pauline, Ducroix, Sophie, Durox, Hélène, Denes, Éric, Abraham, Bruno, Gourdon, Florence, Antoniotti, Odile, Molina, Jean-Michel, Ferret, Samuel, Lascoux-Combe, Caroline, Lafaurie, Matthieu, Colin de Verdiere, Nathalie, Ponscarme, Diane, De Castro, Nathalie, Aslan, Alexandre, Rozenbaum, Willy, Pintado, Claire, Clavel, François, Taulera, Olivier, Gatey, Caroline, Munier, Anne-Lise, Gazaigne, Sandrine, Penot, Pauline, Conort, Guillaume, Lerolle, Nathalie, Leplatois, Anne, Balausine, Stéphanie, Delgado, Jeannine, Timsit, Julie, Tabet, Magda, Gerard, Laurence, Girard, Pierre-Marie, Picard, Odile, Tredup, Jürgen, Bollens, Diane, Valin, Nadia, Campa, Pauline, Bottero, Julie, Lefebvre, Benedicte, Tourneur, Muriel, Fonquernie, Laurent, Wemmert, Charlotte, Lagneau, Jean-Luc, Yazdanpanah, Yazdan, Phung, Bao, Pinto, Adriana, Vallois, Dorothée, Cabras, Ornella, Louni, Françoise, Pialoux, Gilles, Lyavanc, Thomas, Berrebi, Valérie, Chas, Julie, Lenagat, Sophie, Rami, Agathe, Diemer, Myriam, Parrinello, Maguy, Depond, Audrey, Salmon, Dominique, Guillevin, Loïc, Tahi, Tassadit, Belarbi, Linda, Loulergue, Pierre, Zak Dit Zbar, Olivier, Launay, Odile, Silbermann, Benjamin, Leport, Catherine, Alagna, Laura, Pietri, Marie-Pierre, Simon, Anne, Bonmarchand, Manuela, Amirat, Naouel, Pichon, François, Kirstetter, Myriam, Katlama, Christine, Valantin, Marc Antoine, Tubiana, Roland, Caby, Fabienne, Schneider, Luminita, Ktorza, Nadine, Calin, Ruxandra, Merlet, Audrey, Ben Abdallah, Saadia, Weiss, Laurence, Buisson, Martin, Batisse, Dominique, Karmochine, Marina, Pavie, Juliette, Minozzi, Catherine, Jayle, Didier, Castel, Philippe, Derouineau, Jean, Kousignan, Pascale, Eliazevitch, Murielle, Pierre, Isabelle, Collias, Lio, Viard, Jean-Paul, Gilquin, Jacques, Sobel, Alain, Slama, Laurence, Ghosn, Jade, Hadacek, Blanka, Thu-Huyn, Nugyen, Nait-Ighil, Lella, Cros, Agnes, Maignan, Aline, Duvivier, Claudine, Consigny, Paul Henri, Lanternier, Fanny, Shoai-Tehrani, Michka, Touam, Fatima, Jerbi, Saadia, Bodard, Loïc, Jung, Corinne, Goujard, Cécile, Quertainmont, Yann, Duracinsky, Martin, Segeral, Olivier, Blanc, Arnaud, Peretti, Delphine, Cheret, Antoine, Chantalat, Christelle, Dulucq, Marie Josée, Levy, Yves, Lelievre, Jean Daniel, Lascaux, Anne Sophie, Dumont, Cécile, Boue, François, Chambrin, Véronique, Abgrall, Sophie, Kansau, Imad, Raho-Moussa, Mariem, De Truchis, Pierre, Dinh, Aurélien, Davido, Benjamin, Marigot, Dhiba, Berthe, Huguette, Devidas, Alain, Chevojon, Pierre, Chabrol, Amélie, Agher, Nouara, Lemercier, Yvon, Chaix, Fabrice, Turpault, Isabelle, Bouchaud, Olivier, Honore, Patricia, Rouveix, Elisabeth, Reimann, Evelyne, Belan, Alix Greder, Godin Collet, Claire, Souak, Safia, Mortier, Emmanuel, Bloch, Martine, Simonpoli, Anne-Marie, Manceron, Véronique, Cahitte, Isabelle, Hiraux, Emmanuel, Lafon, Erik, Cordonnier, François, Zeng, Ai-Feng, Zucman, David, Majerholc, Catherine, Bornarel, Dominique, Uludag, Agnès, Gellen-Dautremer, Justine, Lefort, Agnès, Bazin, Christine, Daneluzzi, Vincent, Gerbe, Juliette, Jeantils, Vincent, Coupard, Mélissa, Patey, Olivier, Bantsimba, Jonas, Delllion, Sophie, Paz, Pauline Caraux, Cazenave, Benoit, Richier, Laurent, Garrait, Valérie, Delacroix, Isabelle, Elharrar, Brigitte, Vittecoq, Daniel, Bolliot, Claudine, Lepretre, Annie, Genet, Philippe, Masse, Virginie, Perrone, Véronique, Boussard, Jean-Luc, Chardon, Patricia, Froguel, Eric, Simon, Philippe, Tassi, Sylvie, Avettand Fenoel, Véronique, Barin, Francis, Bourgeois, Christine, Cardon, Fanny, Chaix, Marie-Laure, Delfraissy, Jean François, Essat, Asma, Fischer, Hugues, Lecuroux, Camille, Petrov-Sanchez, Ventzislava, Rouzioux, Christine, Saez-Cirion, Asier, Seng, Rémonie, Kuldanek, Kristin, Mullaney, Scott, Young, Carmel, Zucchetti, Antonella, Bevan, Margaret-Ann, McKernan, Sinead, Wandolo, Emily, Richardson, Celia, Youssef, Elaney, Green, Pippa, Faulkner, Sue, Faville, Rebecca, Herman, Sandra, Care, Christine, Blackman, Helen, Bellenger, Katharine, Fairbrother, Keith, Phillips, Andrew, Babiker, Abdel, Delpech, Valerie, Fidler, S, Clarke, Mindy, Fox, Julie, Gilson, R, Goldberg, David, Hawkins, David, Johnson, Anne, Johnson, Margaret, McLean, Ken, Nastouli, Eleni, Post, Frank, Kennedy, N, Pritchard, J, Andrady, U, Rajda, N, Donnelly, C, McKernan, S, Drake, S, Gilleran, G, White, D, Ross, J, Harding, J, Faville, R, Sweeney, J, Flegg, P, Toomer, S, Wilding, H, Woodward, R, Dean, G, Richardson, C, Perry, N, Gompels, M, Jennings, L, Bansaal, D, Browing, M, Connolly, L, Stanley, B, Estreich, S, Magdy, A, O'Mahony, C, Fraser, P, Jebakumar, S P R, David, L, Mette, R, Summerfield, H, Evans, M, White, C, Robertson, R, Lean, C, Morris, S, Winter, A, Faulkner, S, Goorney, B, Howard, L, Fairley, I, Stemp, C, Short, L, Gomez, M, Young, F, Roberts, M, Green, S, Sivakumar, K, Minton, J, Siminoni, A, Calderwood, J, Greenhough, D, DeSouza, C, Muthern, Lisa, Orkin, C, Murphy, S, Truvedi, M, McLean, K, Hawkins, D, Higgs, C, Moyes, A, Antonucci, S, McCormack, S, Lynn, W, Bevan, M, Fox, J, Teague, A, Anderson, J, Mguni, S, Post, F, Campbell, L, Mazhude, C, Russell, H, Carrick, G, Ainsworth, J, Waters, A, Byrne, P, Johnson, M, Kuldanek, K, Mullaney, S, Lawlor, V, Melville, R, Sukthankar, A, Thorpe, S, Murphy, C, Wilkins, E, Ahmad, S, Green, P, Tayal, S, Ong, E, Meaden, J, Riddell, L, Loay, D, Peacock, K, Blackman, H, Harindra, V, Saeed, A M, Allen, S, Natarajan, U, Williams, O, Lacey, H, Care, C, Bowman, C, Herman, S, Devendra, S V, Wither, J, Bridgwood, A, Singh, G, Bushby, S, Kellock, D, Young, S, Rooney, G, Snart, B, Currie, J, Fitzgerald, M, Arumainayyagam, J, Chandramani, S, Rajamanoharan, S, Robinson, T, Taylor, B, Brewer, C, Mayr, Christoph, Schmidt, Wolfgang, Speidel, Andrea, Strohbach, Frank, Arastéh, Keikawus, Cordes, Christiane, Stündel, Manfred, Claus, Jörg, Baumgarten, Axel, Carganico, Andreas, Ingiliz, Patrick, Dupke, Stephan, Freiwald, Matthias, Rausch, Michael, Moll, Arend, Schleehauf, Dorothea, Hintsche, Bettina, Klausen, Gerd, Jessen, Heiko, Jessen, Arne, Köppe, Siegfried, Kreckel, Peter, Schranz, Dietmar, Fischer, Klaus, Schulbin, Hubert, Speer, Miriam, Glaunsinger, Tobias, Wicke, Thomas, Bieniek, Bernhard, Hillenbrand, Heribert, Schlote, Frank, Lauenroth-Mai, Elke, Schuler, Christoph, Schürmann, Dirk, Wesselmann, Hans, Brockmeyer, Norbert, Gehring, Peter, Schmalöer, Dirk, Hower, Martin, Spornraft-Ragaller, Petra, Häussinger, Dieter, Reuter, Stefan, Esser, Stefan, Markus, Rudolf, Kreft, Burkhard, Berzow, Dirk, Christl, Andreas, Meyer, Andreas, Plettenberg, Andreas, Stoehr, Albrecht, Graefe, Katrin, Lorenzen, Thore, Adam, Axel, Schewe, Knut, Weitner, Lutwin, Fenske, Stefan, Hansen, Stefan, Stellbrink, Hans-Jürgen, Wiemer, Dorothea, Hertling, Sandra, Schmidt, Reinhold, Arbter, Peter, Claus, Bernd, Galle, Peter, Jäger, Hans, Jä Gel-Guedes, Eva, Postel, Nils, Fröschl, Monika, Spinner, Christoph, Bogner, Johannes, Salzberger, Bernd, Schölmerich, Jürgen, Audebert, Franz, Marquardt, Ties, Schaffert, Andreas, Schnaitmann, Eiko, Trein, Andreas, Frietsch, Bernhard, Müller, Marcus, Ulmer, Albrecht, Detering-Hübner, Barbara, Kern, Peter, Schubert, Franz, Dehn, Günther, Schreiber, Maria, Güler, Cengiz, Schmidt, Daniel, Meixenberger, Karolin, Medical Microbiology & Infectious Diseases, Internal Medicine, Virology, Pediatrics, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Global Health, Infectious diseases, APH - Aging & Later Life, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, VU University medical center, Surgery, AMS - Rehabilitation & Development, APH - Quality of Care, Psychiatry, Pediatric surgery, Neurology, Public and occupational health, APH - Mental Health, Pathology, Cardiology, ACS - Heart failure & arrhythmias, Anesthesiology, IOO, Rehabilitation medicine, Obstetrics and gynaecology, General practice, Gastroenterology and hepatology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Medical oncology laboratory, Hematology, Epidemiology and Data Science, Physiology, Microbes in Health and Disease (MHD), University of Oxford, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Amsterdam UMC - Amsterdam University Medical Center, The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Johns Hopkins University (JHU), Universität Zürich [Zürich] = University of Zurich (UZH), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Institut Pasteur [Paris] (IP), This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., We thank K. Fransen and G. Vanham for help with the Belgian data, O. Ratmann for help in identifying the Dutch clusters, K. Kusejko for testing for additional VB individuals in the SHCS, B. Foley for help with genome sharing, B. Dearlove and L. Thomson for help with software, and J. Herbeck and three other reviewers for helpful suggestions., Contributors and affiliations are listed in the supplementary materials., Department of Medicine, University of Helsinki, Infektiosairauksien yksikkö, HUS Inflammation Center, and Clinicum

Subjects
Adult, Male, HIV-1/genetics, Genotype, Anti-HIV Agents, Evolution, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections/drug therapy, selection, HIV Infections, Genome, Viral, heritability, epidemic, human-immunodeficiency-virus, Evolution, Molecular, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Viral, Phylogeny, Netherlands, Multidisciplinary, Genome, model, Virulence, transmission, Molecular, setpoint viral load, reverse-transcriptase, dynamics, Viral Load, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 3121 General medicine, internal medicine and other clinical medicine, Anti-HIV Agents/therapeutic use, Mutation, HIV-1, Female, progression
Abstract

Comment in Does HIV-1 virulence matter in the ART era? Lewitus E, Rolland M. Med (N Y). 2022 Apr 8;3(4):217-219. doi: 10.1016/j.medj.2022.03.003. PMID: 35590149; International audience; We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Published
2022

38. Physician Training for Electrocardiogram Interpretation: A Systematic Review and Meta-Analysis

Author

So-Young Oh, David A. Cook, Pascal W.M. Van Gerven, Joseph Nicholson, Hilary Fairbrother, Frank W.J.M. Smeenk, and Martin V. Pusic

Subjects
MEDICAL-STUDENTS, CLINICAL CARDIOLOGY, LEARNING OUTCOMES, Students, Medical, Education, Medical, General Medicine, ECG INTERPRETATION, ARRHYTHMIAS COMMITTEE, Education, SCIENTIFIC STATEMENT, HEALTH-PROFESSIONS EDUCATION, Electrocardiography, OF-CARDIOLOGY-FOUNDATION, AMERICAN-HEART-ASSOCIATION, Physicians, DELIBERATE PRACTICE, Humans, Computer-Assisted Instruction
Abstract

PURPOSE: Using electrocardiogram (ECG) interpretation as an example of a widely taught diagnostic skill, the authors conducted a systematic review and meta-analysis to demonstrate how research evidence on instruction in diagnosis can be synthesized to facilitate improvement of educational activities (instructional modalities, instructional methods, and interpretation approaches), guide the content and specificity of such activities, and provide direction for research. METHOD: The authors searched PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, PsycInfo, CINAHL, ERIC, and Web of Science databases through February 21, 2020, for empirical investigations of ECG interpretation training enrolling medical students, residents, or practicing physicians. They appraised study quality with the Medical Education Research Study Quality Instrument and pooled standardized mean differences (SMDs) using random effects meta-analysis. RESULTS: Of 1,002 articles identified, 59 were included (enrolling 17,251 participants). Among 10 studies comparing instructional modalities, 8 compared computer-assisted and face-to-face instruction, with pooled SMD 0.23 (95% CI, 0.09, 0.36) indicating a small, statistically significant difference favoring computer-assisted instruction. Among 19 studies comparing instructional methods, 5 evaluated individual versus group training (pooled SMD 0.35 favoring group study [95% CI, 0.06, 0.63]); 4 evaluated peer-led versus faculty-led instruction (pooled SMD 0.38 favoring peer instruction [95% CI, 0.01, 0.74]); and 4 evaluated contrasting ECG features (e.g., QRS width) from 2 or more diagnostic categories versus routine examination of features within a single ECG or diagnosis (pooled SMD 0.23 not significantly favoring contrasting features [95% CI, -0.30, 0.76]). Eight studies compared ECG interpretation approaches, with pooled SMD 0.92 (95% CI, 0.48, 1.37) indicating a large, statistically significant effect favoring more systematic interpretation approaches. CONCLUSIONS: Some instructional interventions appear to improve learning in ECG interpretation; however, many evidence-based instructional strategies are insufficiently investigated. The findings may have implications for future research and design of training to improve skills in ECG interpretation and other types of visual diagnosis.

Published
2022

39. Massively parallel reporter assays discover de novo exonic splicing mutants in paralogs of Autism genes

Author

Christy L. Rhine, Christopher Neil, Jing Wang, Samantha Maguire, Luke Buerer, Mitchell Salomon, Ijeoma C. Meremikwu, Juliana Kim, Natasha T. Strande, and William G. Fairbrother

Subjects
Cancer Research, Pervasive Developmental Disorders, genetic structures, Autism Spectrum Disorder, Epidemiology, Autism, RNA Splicing, Social Sciences, Pathogenesis, QH426-470, Research and Analysis Methods, Pathology and Laboratory Medicine, behavioral disciplines and activities, Cell Line, Medical Conditions, Developmental Neuroscience, Cell Signaling, mental disorders, Medicine and Health Sciences, Genetics, Psychology, Gene Disruption, Humans, Gene Regulatory Networks, Genetic Predisposition to Disease, Calcium Signaling, Molecular Biology Techniques, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Silent Mutation, Gene Mapping, Biology and Life Sciences, RNA-Binding Proteins, Genomics, Cell Biology, Exons, Pedigree, Phenotype, Neurology, Neurodevelopmental Disorders, Medical Risk Factors, Developmental Psychology, Mutation, Exon Mapping, Research Article, Neuroscience, Signal Transduction
Abstract

To determine the contribution of defective splicing in Autism Spectrum Disorders (ASD), the most common neurodevelopmental disorder, a high throughput Massively Parallel Splicing Assay (MaPSY) was employed and identified 42 exonic splicing mutants out of 725 coding de novo variants discovered in the sequencing of ASD families. A redesign of the minigene constructs in MaPSY revealed that upstream exons with strong 5’ splice sites increase the magnitude of skipping phenotypes observed in downstream exons. Select hits were validated by RT-PCR and amplicon sequencing in patient cell lines. Exonic splicing mutants were enriched in probands relative to unaffected siblings -especially synonymous variants (7.5% vs 3.5%, respectively). Of the 26 genes disrupted by exonic splicing mutations, 6 were in known ASD genes and 3 were in paralogs of known ASD genes. Of particular interest was a synonymous variant in TNRC6C - an ASD gene paralog with interactions with other ASD genes. Clinical records of 3 ASD patients with TNRC6C variant revealed respiratory issues consistent with phenotypes observed in TNRC6 depleted mice. Overall, this study highlights the need for splicing analysis in determining variant pathogenicity, especially as it relates to ASD., Author summary Autism Spectrum Disorders (ASD) is the most common neurodevelopmental disorder that presents with both phenotypic and genetic heterogeneity. Before genetically defined therapeutic approaches can be applied to the treatment of ASD, it is crucial to understand the genetic basis of the disorder. Tremendous effort by consortiums, such as the Simon Foundation for Autism Research Initiative, has led to the identification of variants and, in turn, genes associated with ASD. However, the effect of ASD variants have on the process of splicing is often not fully considered when assessing ASD risk genes. Using a high-throughput splicing assay, MaPSy, ~6.3% of ASD-associated variants affected splicing, highlighting a substantial contribution of defective splicing to ASD. This analysis led to identification of genes, such as TNRC6C, that warrant further investigation with respect to ASD risk.

Published
2022

40. Children living with HIV in Europe: do migrants have worse treatment outcomes?

Author

Chappell, E., Kohns Vasconcelos, M., Goodall, R. L., Galli, L., Goetghebuer, T., Noguera-Julian, A., Rodrigues, L. C., Scherpbier, H., Smit, C., Bamford, A., Crichton, S., Navarro, M. L., Ramos, J. T., Warszawski, J., Spolou, V., Chiappini, E., Venturini, E., Prata, F., Kahlert, C., Marczynska, M., Marques, L., Naver, L., Thorne, C., Gibb, D. M., Giaquinto, C., Judd, A., Collins, I. J., Goodall, R., Rodrigues, L., Duff, C., Gomezpena, D., Jackson, C., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Granier, M., Labrune, P., Lachassine, E., Dollfus, C., Levine, M., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Monpoux, F., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., de Villeneuve, A., Lalande, M., de Flandres, J., Mazingue, F., Partisani, M. L., de Martino, M., Angelo Tovo, P., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Kinderziekenhuis, E., van der Kuip, M., Pajkrt, D., Scherpbier, H. J., de Boer, C., Weijsenfeld, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Henriet, S. S. V., van Aerde, M. K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Burger, D., Scholvinck, E. H., de Groot-de Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Loeffen, Y. G. T., Wolfs, T. F. W., Nauta, N., Schuurman, R., Hofstra, L. M., Wensing, A. M. J., Reiss, P., Zaheri, S., Boyd, A. C., Bezemer, D. O., van Sighem, A. I., Wit, F. W. M. N., Hillebregt, M. M. J., Woudstra, T. J., Bergsma, D., van de Sande, L., Rutkens, T., van der Vliet, S., Lelivelt, K. J., Scheijgrond, A., de Groot, L., van den Akker, M., Bakker, Y., EI Berkaoui, A., Bezemer, M., Bretin, N., Djoechro, E., Groters, M., Kruijne, E., Lodewijk, C., Lucas, E., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., Visser, K. M., Witte, E. C., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Teixeira, C., Fernandes, A., Soler-Palacin, P., Antoinette Frick, M., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Fortuny, C., Jose Mellado, M., Escosa, L., Garcia Hortelano, M., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto-Tato, L., Epalza, C., Tomas Ramos, J., Guillen, S., Saavedra, J., Santos, M., Santiago, B., de Ory, S. J., Carrasco, I., Munoz-Fernandez, M. A., Angel Roa, M., Penin, M., Martinez, J., Badillo, K., Onate, E., Pocheville, I., Garrote, E., Colino, E., Gomez Sirvent, J., Garzon, M., Roman, V., Angulo, R., Neth, O., Falcon, L., Terol, P., Luis Santos, J., Moreno, D., Lendinez, F., Peromingo, E., Uberos, J., Ruiz, B., Grande, A., Jose Romero, F., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Collado, P., Antonio Couceiro, J., Vila, L., Calvino, C., Isabel Piqueras, A., Oltra, M., Gavilan, C., Montesinos, E., Dapena, M., Alvarez, C., Jimenez, B., Gloria Andres, A., Marugan, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., del Prado, Y. R., Navernaver, L., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Crisinel, P. A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, C., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Sultan-Beyer, L., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Yerly, S., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Foster, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Prevost, M. L., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou - Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rosie Hague, D., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Department of Sciences for Woman and Child's Health, Florence University, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, Infectious diseases, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, Global Health, APH - Aging & Later Life, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, 1, Elizabeth Chappell, 2 3 4, Malte Kohns Vasconcelo, L Goodall 1, Ruth, 5, Luisa Galli, 6, Tessa Goetghebuer, 9 10, Antoni Noguera-Julian 7 8, C Rodrigues 2, Laura, Scherpbier 11, Henriette, Smit 12, Colette, 1 13 14, Alasdair Bamford, 1, Siobhan Crichton, Luisa Navarro 10 15 16 17, Marissa, T Ramos 18, Jose, Warszawski 19 20, Josiane, Spolou 21, Vana, 5, Elena Chiappini, 5, Elisabetta Venturini, Prata 22, Filipa, Kahlert 23, Christian, Marczynska 24, Magdalena, Marques 25, Laura, Naver 26, Lar, Thorne 14, Claire, M Gibb 1, Diana, Giaquinto 27, Carlo, 1, Ali Judd, 1, Intira Jeannie Collin, Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC), European, Goodall, Ruth, Rodrigues, Laura, Duff, Charlotte, Gomezpena, Daniel, Jackson, Charlotte, Lundin, Rebecca, Mangiarini, Laura, Milanzi, Edith, Nardone, Alessandra, Hainaut, Marc, Van der Kelen, Evelyne, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Granier, Michèle, Labrune, Philippe, Lachassine, Eric, Dollfus, Catherine, Levine, Martine, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Monpoux, Fabrice, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, de Villeneuve, Arnaud, Lalande, Muriel, de Flandres, Jeanne, Mazingue, Françoise, Luisa Partisani, Maria, de Martino, Maurizio, Angelo Tovo, Pier, Gabiano, Clara, Carloni, Ine, Larovere, Domenico, Baldi, Francesco, Miniaci, Angela, Pession, Andrea, Badolato, Raffaele, Pantò, Grazia, Anastasio, Elisa, Montagnani, Carlotta, Bianchi, Leila, Allodi, Alessandra, Di Biagio, Antonio, Grignolo, Sara, Giacomet, Vania, Marchisio, Paola, Banderali, Giuseppe, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, DI COSTANZO, Pasquale, LO VECCHIO, Andrea, Donà, Daniele, Rampon, Osvalda, Romano, Amelia, Dodi, Icilio, Esposito, Susanna, Zuccaro, Valentina, Zanaboni, Domenico, Consolini, Rita, Bernardi, Stefania, Genovese, Orazio, Cristiano, Letizia, Mazza, Antonio, Garazzino, Silvia, Mignone, Federica, Silvestro, Erika, Portelli, Vincenzo, Pediatric surgery, Pediatrics, and Virology

Subjects
children, Europe, HIV, migrant, mortality, Adolescent, Child, Humans, Treatment Outcome, Viral Load, Anti-HIV Agents, HIV Infections, Transients and Migrants, medicine.medical_treatment, Human immunodeficiency virus (HIV), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], medicine.disease_cause, 0302 clinical medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, health care economics and organizations, Health Policy, Hazard ratio, virus diseases, Immunosuppression, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, population characteristics, 0305 other medical science, Viral load, geographic locations, education, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, 030505 public health, business.industry, Proportional hazards model, medicine.disease, Confidence interval, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Contains fulltext : 249078.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged

Published
2022

41. An analysis of English national policy approaches to health inequalities: ‘transforming children and young people’s mental health provision’ and its consultation process

Author

Griffin, N., Wistow, J., Fairbrother, H., Holding, E., Sirisena, M., Powell, K., and Summerbell, C.

Subjects
Mental Health, Adolescent, Health Policy, Public Health, Environmental and Occupational Health, COVID-19, Humans, Health Status Disparities, Child, Pandemics, Referral and Consultation
Abstract

Background A national policy for England, published in 2017, entitled ‘Transforming Children and Young People’s Mental Health Provision’ aimed to address the increasing prevalence mental health problems in children and tackle inequalities. In the context of this policy’s implementation as ongoing and the effects of the Covid-19 pandemic, the need for appropriate, timely and ongoing national government commitment is vital. Methods A narrative review using a problem representation evaluation [1], we critiqued the policy and related consultation documents using a social determinants of health perspective. We also reviewed wider policy discourses through engaging with stakeholder responses, providing an innovative methodological contribution to scholarship on public health policy and health inequalities. Results We found absences and oversights in relation to inequalities (most notably the lack of acknowledgement that mental health can cause inequalities), access, workforce capacity, and the impacts of cuts and austerity on service provision. We suggest these inadequacies may have been avoided if stakeholder responses to the consultation process had been more meaningfully addressed. We illustrate how ‘problems’ are discursively created through the process of policy development, justified using specific types of evidence, and that this process is politically motivated. Local policy makers have a critical role in translating and adapting national policy for their communities but are constrained by absences and oversights in relation to health inequalities. Conclusions This narrative review illustrates how policy discourse frames and produces ‘problems’, and how the evidence used is selected and justified politically. This review contributes to the existing transdisciplinary field of knowledge about how using methods from political and social science disciplines can reveal new insights when critiquing and influencing policy approaches to health inequalities.

Published
2022

42. Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study

Author

Yue Fu, Wenqiong Wu, Sayumi Yamazoe, Changlei Sun, Liang Zeng, Qi Liu, Wayne J. Fairbrother, Jie Lin, Kui Lin, Jeffrey Tom, and Steven T. Staben

Subjects
Phosphatase, Ligands, Proof of Concept Study, 01 natural sciences, Cell Line, Small Molecule Libraries, Dephosphorylation, 03 medical and health sciences, Ubiquitin, Protein Phosphatase 1, Drug Discovery, Humans, Phosphorylation, Protein kinase B, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Kinase, Drug discovery, Phosphotransferases, Small molecule, 0104 chemical sciences, Cell biology, ErbB Receptors, 010404 medicinal & biomolecular chemistry, biology.protein, Molecular Medicine, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-akt
Abstract

Heterobifunctional molecules have proven powerful tools to induce ligase-dependent ubiquitination of target proteins. We describe here a chemical strategy for controlling a different post-translational modification (PTM): phosphorylation. Heterobifunctional molecules were designed to promote the proximity of a protein phosphatase (PP1) to protein targets. The synthesized molecules induced the PP1-dependent dephosphorylation of AKT and EGFR. To our knowledge, this work represents the first examples of small molecules recruiting non-native partners to induce removal of a PTM.

Published
2019

43. Promoting the health of children and young people who migrate: reflections from four regional reviews

Author

Melody Smith, Victoria Whitakker, Deirdre Hogan, Bukola Salami, Jacqui O'Riordan, Hannah Fairbrother, Christa Fouché, Karen Hoare, Jill Thompson, Penny Curtis, Bethany Taylor, and Grace Spencer

Subjects
Economic growth, Adolescent, Universities, media_common.quotation_subject, Poison control, Health Promotion, Global Health, Suicide prevention, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, Promotion (rank), Children and young people, Political science, Injury prevention, Global health, Humans, 030212 general & internal medicine, Child, Migration, media_common, Transients and Migrants, 030505 public health, Public Health, Environmental and Occupational Health, Human factors and ergonomics, Systematic review, Global health promotion, 0305 other medical science
Abstract

Calls to enhance the health of migrant population sub-groups are strengthening, with increasing evidence documenting the relationship between migration and health outcomes. Despite the importance of migration to global health promotion, little research has focused on the health experiences of young migrants. As part of a Worldwide University Network project, we completed four systematic reviews examining the existing evidence base on the health experiences of children and young people who migrate. In this commentary, we share commonalities with the international evidence but also reflect on some of the challenges, omissions and limitations. These insights expose significant gaps and methodological shortcomings in the evidence – providing space for new research that seeks to identify the influences on migrant children’s health.

Published
2019

44. The decline in youth drinking in England—is everyone drinking less? A quantile regression analysis

Author

Oldham, Melissa, Callinan, Sarah, Whitaker, Victoria, Fairbrother, Hannah, Curtis, Penny, Meier, Petra, Livingston, Michael, and Holmes, John

Subjects
Research Report, Male, polarization, Adolescent, Research Reports, Underage Drinking, young people, Cross-Sectional Studies, England, youth drinking, Humans, Regression Analysis, Alcohol consumption, Female, collectivity, trend analysis, Child
Abstract

Background and Aims:\ud \ud Youth alcohol consumption has declined significantly during the past 15 years in many high‐income countries, which may have significant public health benefits. However, if the reductions in drinking occur mainly among lighter drinkers who are at lower risk, then rates of alcohol‐related harm among young people today and adults in future may not fall in line with consumption. There is conflicting evidence from Swedish school studies, with some suggesting that all young people are drinking less, while others suggest that alcohol consumption among heavier drinkers may be stable or rising while average consumption declines. This paper extends the geographical focus of previous research and examines whether the decline in youth drinking is consistent across the consumption distribution in England.\ud \ud Design: \ud \ud Quantile regression of 15 waves of repeat cross‐sectional survey data.\ud \ud Setting: \ud \ud England, 2001–16.\ud \ud Participants: \ud \ud A total of 31 882 schoolchildren (50.7% male) aged 11–15 who responded to the Smoking Drinking and Drug Use among Young People surveys.\ud \ud Measurements: \ud \ud Past‐week alcohol consumption in UK units at each fifth percentile of the consumption distribution.\ud \ud Findings: \ud \ud Reductions in alcohol consumption occurred at all percentiles of the consumption distribution analysed between 2001 and 2016, but the magnitude of the decline differed across percentiles. The decline in consumption at the 90th percentile [β = −0.21, confidence interval (CI) = −0.24, −0.18] was significantly larger than among either lighter drinkers at the 50th percentile (β = −0.02, CI = −0.02, −0.01) or heavier drinkers at the 95th percentile (β = −0.16, CI = −0.18, −0.13).\ud \ud Conclusions: \ud \ud Alcohol consumption among young people in England appears to be declining across the consumption distribution, and peaks among heavy drinkers. The magnitude of this decline differs significantly between percentiles of the consumption distribution, with consumption falling proportionally less among the lightest, moderate and very heaviest youth drinkers.

Published
2019

45. Exploring the Patient's Experience of Receiving Clinical Care Which Incorporates the Use of Mobile Technology at the Bedside

Author

J, Warrilow, L, Pho, C, Murley, A, Jones, and G, Fairbrother

Subjects
Inpatients, Technology, Research Design, Surveys and Questionnaires, Humans, Hospitals
Abstract

Research-based insight into patient's experiences of mobile technology at the bedside in the hospital setting remains limited. This research project aims to explore patient's experience.This mixed method pre and post study aimed to explore the patient experience in relation to this and also test whether introducing further bedside technology (beyond the workstation on wheels) had an effect on the patient experience. Questionnaires and interviews were conducted among inpatient samples prior to and one year post introduction of a suite of new bedside technologies.Pre and post patient survey results (pre: n=82; post: n=98) suggested that mixed views and perceptions existed and that some of these were associated with primary demographics such as age. At post-test, attitudes about bedside technology were found to be more positive, and feedback about care quality was found to be unchanged, Baseline patient interview findings (n=15) highlight the social ubiquity of technology as a driver of positive attitude in the digital health context.The addition of new bedside technology is very well received by patients and was not perceived to impact on care quality.

Published
2021

46. A critique of the English national policy from a social determinants of health perspective using a realist and problem representation approach: the 'Childhood Obesity: a plan for action' (2016, 2018, 2019)

Author

Naomi Griffin, Sophie M. Phillips, Frances Hillier-Brown, Jonathan Wistow, Hannah Fairbrother, Eleanor Holding, Katie Powell, and Carolyn Summerbell

Subjects
Pediatric Obesity, Childhood Obesity, Social Determinants of Health, Health Policy, Research, Public Health, Environmental and Occupational Health, Health Status Disparities, Policy, Humans, Public Health, Public aspects of medicine, RA1-1270, Child, Policy Making, Health inequalities
Abstract

Background The UK government released Chapter 1 of the ‘Childhood Obesity: a plan for action’ (2016), followed by Chapter 2 (2018) and preliminary Chapter 3 was published for consultation in 2019 (hereon collectively ‘The Policy’). The stated policy aims were to reduce the prevalence of childhood obesity in England, addressing disparities in health by reducing the gap (approximately two-fold) in childhood obesity between those from the most and least deprived areas. Methods Combining a realist approach with an analysis of policy discourses, we analysed the policies using a social determinants of health (SDH) perspective (focusing on socio-economic inequalities). This novel approach reveals how the framing of policy ‘problems’ leads to particular approaches and interventions. Results While recognising a social gradient in relation to obesity measures, we critique obesity problem narratives. The Policy included some upstream, structural approaches (e.g. restrictions in food advertising and the soft-drinks industry levy). However, the focus on downstream individual-level behavioural approaches to reduce calorie intake and increase physical activity does not account for the SDH and the complexity and contestedness of ‘obesity’ and pays insufficient attention to how proposals will help to reduce inequalities. Our findings illustrate that individualising of responsibility to respond to what wider evidence shows is structural inequalities, can perpetuate damaging narratives and lead to ineffective interventions, providing caution to academics, practitioners and policy makers (local and national), of the power of problem representation. Our findings also show that the problem framing in The Policy risks reducing important public health aims to encourage healthy diets and increase opportunities for physical activity (and the physical and mental health benefits of both) for children to weight management with a focus on particular children. Conclusions We propose an alternative conceptualisation of the policy ‘problem’, that obesity rates are illustrative of inequality, arguing there needs to be policy focus on the structural and factors that maintain health inequalities, including poverty and food insecurity. We hope that our findings can be used to challenge and strengthen future policy development, leading to more effective action against health inequalities and intervention-generated inequalities in health.

Published
2021

47. POSNOC-POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes

Author

Wei Tan, Alastair Thompson, Alan Montgomery, Sarah Craig, Laura Ternent, Eleanor Mitchell, Lelia Duley, Ian Ellis, Alistair Ring, Nicole Francis, Hannah Price, David Dodwell, Elizabeth Miles, Rebecca Haydock, Margaret Childs, Mara Ozolins, Diane Whitham, Apostolos Fakis, David Whynes, Patricia Fairbrother, Robert Newcombe, Malcolm Reed, Daniel Davis, Tara Homer, Kathryn Monson, Ramsey Cutress, Valerie Jenkins, Lesley Fallowfield, Clare Brittain, Daniel Rea, Judith Bliss, Amit Goyal, G Bruce Mann, Robert E Coleman, Shabina Sadiq, Heath Badger, Rachel Helen Haines, Mickey Lewis, Daniel Megias, Zohal Nabi, Preetinder Singh, Andrei Caraman, Romaana Mir, Teresa Grieve, Clare Upton, Aisha Shafayat, Charlotte Gidman, Flonda Probert, Lisa Paksec, Rose Lucas, Annette Dempsey, Rochelle Thornton, Roeum Butt, Peter Barrett Lee, Julie Wolfarth, and Peter Dubsky

Subjects
medicine.medical_specialty, Breast surgery, medicine.medical_treatment, Breast Neoplasms, breast tumours, law.invention, Breast cancer, Randomized controlled trial, adult radiotherapy, law, Internal medicine, Breast-conserving surgery, Adjuvant therapy, Medicine, Humans, Mastectomy, business.industry, General Medicine, Sentinel node, breast surgery, medicine.disease, Radiation therapy, Lymphatic Metastasis, Axilla, Quality of Life, Lymph Node Excision, Female, Radiotherapy, Adjuvant, Surgery, business
Abstract

IntroductionACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence.Methods and analysisPOSNOC is a pragmatic, multicentre, non-inferiority, international trial with participants randomised in a 1:1 ratio. Women are eligible if they have T1/T2, unifocal or multifocal invasive breast cancer, and 1 or 2 macrometastases at sentinel node biopsy, with or without extranodal extension. In the intervention group women receive adjuvant therapy alone, in the standard care group they receive ANC or axillary RT. In both groups women receive adjuvant therapy, according to local guidelines. This includes systemic therapy and, if indicated, RT to breast or chest wall. The UK Radiotherapy Trials Quality Assurance Group manages the in-built radiotherapy quality assurance programme. Primary endpoint is 5-year axillary recurrence. Secondary outcomes are arm morbidity assessed by Lymphoedema and Breast Cancer Questionnaire and QuickDASH questionnaires; quality of life and anxiety as assessed with FACT B+4 and State/Trait Anxiety Inventory questionnaires, respectively; other oncological outcomes; economic evaluation using EQ-5D-5L. Target sample size is 1900. Primary analysis is per protocol. Recruitment started on 1 August 2014 and as of 9 June 2021, 1866 participants have been randomised.Ethics and disseminationProtocol was approved by the National Research Ethics Service Committee East Midlands—Nottingham 2 (REC reference: 13/EM/0459). Results will be submitted for publication in peer-reviewed journals.Trial registration numberISRCTN54765244;NCT0240168Cite Now

Published
2021

48. Malignancies among children and young people with HIV in Western and Eastern Europe and Thailand the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Author

Chappell, E., Turkova, A., Goetghebuer, T., Jackson, C., Chiappini, E., Galli, L., Gingaras, C., Judd, A., Spoulou, V., Lisi, C., Ansone, S., Wolfs, T., Marczynska, M., Ene, L., Plotnikova, Y., Voronin, E., Samarina, A., Jourdain, G., Ngo-Giang-Huong, N., Fortuny, C., Navarro, M. L., Ramos, J. T., Naver, L., Crisinel, P. -A., Bailey, H., Malyuta, R., Volokha, A., Bamford, A., Crichton, S., Foster, C., Thorne, C., Collins, I. J., Giaquinto, C., Gibb, D. M., Critchton, S., Duff, C., Goodall, R., Gomezpena, D., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., de Martino, M., Tovo, P. A., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Venturini, E., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona', D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S. V., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-De Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A. I., Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Miloenko, M., Labutina, S., Soler-Palacin, P., Frick, M. A., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Noguera-Julian, A., Mellado, M. J., Escosa, L., Hortelano, M. G., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto, L., Guillen, S., Saavedra, J., Santos, M., Munoz, M. A., Ruiz, B., Fernandez, C., Phee, M., de Ory, S. J., Alvarez, S., Roa, M. A., Beceiro, J., Martinez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Sirvent, J. G., Garzon, M., Roman, V., Montesdeoca, A., Mateo, M., Munoz, M. J., Angulo, R., Neth, O., Falcon, L., Terol, P., Santos, J. L., Moreno, D., Lendinez, F., Grande, A., Romero, F. J., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Couceiro, J. A., Perez, A., Piqueras, A. I., Breton, R., Segarra, I., Gavilan, C., Jareno, E., Montesinos, E., Dapena, M., Alvarez, C., Andres, A. G., Marugan, V., Ochoa, C., Alfayate, S., Menasalvas, A. I., de Miguel, E., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. A., Yerly, S., Wannarit, P., Techakunakorn, P., Hansudewechakul, R., Wanchaitanawong, V., Theansavettrakul, S., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Kiseleva, G., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Le Prevost, M., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou-Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Hague, D. R., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Chappell, E., Turkova, A., Goetghebuer, T., Jackson, C., Chiappini, E., Galli, L., Gingaras, C., Judd, A., Spoulou, V., Lisi, C., Ansone, S., Wolfs, T., Marczynska, M., Ene, L., Plotnikova, Y., Voronin, E., Samarina, A., Jourdain, G., Ngo-Giang-Huong, N., Fortuny, C., Navarro, M. L., Ramos, J. T., Naver, L., Crisinel, P. -A., Bailey, H., Malyuta, R., Volokha, A., Bamford, A., Crichton, S., Foster, C., Thorne, C., Collins, I. J., Giaquinto, C., Gibb, D. M., Critchton, S., Duff, C., Goodall, R., Gomezpena, D., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., de Martino, M., Tovo, P. A., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Venturini, E., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S. V., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-De Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A. I., Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Miloenko, M., Labutina, S., Soler-Palacin, P., Frick, M. A., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Noguera-Julian, A., Mellado, M. J., Escosa, L., Hortelano, M. G., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto, L., Guillen, S., Saavedra, J., Santos, M., Munoz, M. A., Ruiz, B., Fernandez, C., Phee, M., de Ory, S. J., Alvarez, S., Roa, M. A., Beceiro, J., Martinez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Sirvent, J. G., Garzon, M., Roman, V., Montesdeoca, A., Mateo, M., Munoz, M. J., Angulo, R., Neth, O., Falcon, L., Terol, P., Santos, J. L., Moreno, D., Lendinez, F., Grande, A., Romero, F. J., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Couceiro, J. A., Perez, A., Piqueras, A. I., Breton, R., Segarra, I., Gavilan, C., Jareno, E., Montesinos, E., Dapena, M., Alvarez, C., Andres, A. G., Marugan, V., Ochoa, C., Alfayate, S., Menasalvas, A. I., de Miguel, E., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. A., Yerly, S., Wannarit, P., Techakunakorn, P., Hansudewechakul, R., Wanchaitanawong, V., Theansavettrakul, S., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Kiseleva, G., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Le Prevost, M., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou-Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Hague, D. R., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., and Yannoulias, A.

Subjects
Adult, Male, Acquired Immunodeficiency Syndrome, Adolescent, Infant, HIV, HIV Infections, Eastern, Adolescents, Newborn, Thailand, Europe, malignancie, Neoplasms, malignancies, Humans, Children, Aged, Child, Europe, Eastern, Infant, Newborn
Abstract

Objectives: Investigate trends over time and predictors of malignancies among children and young people with HIV. Design: Pooled data from 17 cohorts in 15 countries across Europe and Thailand. Methods: Individuals diagnosed with HIV and presenting to paediatric care less than 18 years of age were included. Time at risk began at birth for children with documented vertically acquired HIV, and from first HIV-care visit for others. Children were followed until death, loss-to-follow-up, or last visit in paediatric or adult care (where data after transfer to adult care were available). Rates of reported malignancies were calculated overall and for AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (NADM) separately. Risk factors for any malignancy were explored using Poisson regression, and for mortality following a malignancy diagnosis using Cox regression. Results: Among 9632 individuals included, 140 (1.5%) were ever diagnosed with a malignancy, of which 112 (80%) were ADM. Overall, the rate of any malignancy was 1.18 per 1000 person-years; the rate of ADM decreased over time whereas the rate of NADM increased. Male sex, being from a European cohort, vertically acquired HIV, current severe immunosuppression, current viral load greater than 400 copies/ml, older age, and, for those not on treatment, earlier calendar year, were risk factors for a malignancy diagnosis. Fifty-eight (41%) individuals with a malignancy died, a median 2.4 months (IQR 0.6-8.8) after malignancy diagnosis. Conclusion: The rate of ADM has declined since widespread availability of combination ART, although of NADM, there was a small increase. Mortality following a malignancy was high, warranting further investigation.

Published
2021

49. Youth drinking in decline: What are the implications for public health, public policy and public debate?

Author

John Holmes, Hannah Fairbrother, Michael Livingston, Petra Sylvia Meier, Melissa Oldham, Amy Pennay, and Victoria Whitaker

Subjects
Adult, Adolescent, Alcohol Drinking, Government, Health Policy, Medicine (miscellaneous), Humans, Public Policy, Public Health, Underage Drinking, Policy Making, Uncategorized
Abstract

Youth drinking has declined across most high-income countries in the last 20 years. Although researchers and commentators have explored the nature and drivers of decline, they have paid less attention to its implications. This matters because of the potential impact on contemporary and future public health, as well as on alcohol policy-making. This commentary therefore considers how youth drinking trends may develop in future, what this would mean for public health, and what it might mean for alcohol policy and debate.\ud \ud \ud \ud We argue that the decline in youth drinking is well-established and unlikely to reverse, despite smaller declines and stabilising trends in recent years. Young people also appear to be carrying their lighter drinking into adulthood in at least some countries. This suggests we should expect large short- and long-term public health benefits. The latter may however be obscured in population-level data by increased harm arising from earlier, heavier drinking generations moving through the highest risk points in the life course.\ud \ud \ud \ud The likely impact of the decline in youth drinking on public and policy debate is less clear. We explore the possibilities using two model scenarios, the reinforcement and withdrawal models. In the reinforcement model, a ‘virtuous’ circle of falling alcohol consumption, increasing public support for alcohol control policies and apparent policy successes facilitates progressive strengthening of policy, akin to that seen in the tobacco experience. In the withdrawal model, policy-makers turn their attention to other problems, public health advocates struggle to justify proposed interventions and existing policies erode over time as industry actors reassert and strengthen their partnerships with government around alcohol policy. We argue that disconnects between the tobacco experience and the reinforcement model make the withdrawal model a more plausible scenario. We conclude by suggesting some tentative ways forward for public health actors working in this space.

Published
2021

50. Best-BRA (Is subpectoral or pre-pectoral implant placement best in immediate breast reconstruction?) A protocol for a pilot randomised controlled trial of subpectoral versus pre-pectoral immediate implant-based breast reconstruction in women following mastectomy

Author

Chris Holcombe, Ramsey I. Cutress, Steven Thrush, Katherine Fairhurst, Jodi Taylor, Patricia Fairbrother, Shelley Potter, Jo Skillman, Chris Metcalfe, Kirsty Roberts, J. Athene Lane, Lisa Whisker, Nicola Mills, William Hollingworth, and Clare Clement

Subjects
medicine.medical_specialty, Breast Implants, Mammaplasty, medicine.medical_treatment, Breast surgery, Breast Neoplasms, Pilot Projects, breast tumours, law.invention, Breast cancer, Randomized controlled trial, law, medicine, Humans, HEB, Breast Implantation, Mastectomy, subpectoral, Randomized Controlled Trials as Topic, Protocol (science), business.industry, pre-pectoral, implant-based breast reconstruction, General Medicine, breast surgery, medicine.disease, pilot trial, plastic & reconstructive surgery, Physical therapy, Medicine, Surgery, Female, Observational study, Implant, QuinteT Recruitment Intervention (QRI), business, Breast reconstruction, randomised controlled trial, qualitative research
Abstract

BackgroundImplant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure following mastectomy. IBBR techniques are evolving rapidly, with mesh-assisted subpectoral reconstruction becoming the standard of care and more recently, prepectoral techniques being introduced. These muscle-sparing techniques may reduce postoperative pain, avoid implant animation and improve cosmetic outcomes and have been widely adopted into practice. Although small observational studies have failed to demonstrate any differences in the clinical or patient-reported outcomes of prepectoral or subpectoral reconstruction, high-quality comparative evidence of clinical or cost-effectiveness is lacking. A well-designed, adequately powered randomised controlled trial (RCT) is needed to compare the techniques, but breast reconstruction RCTs are challenging. We, therefore, aim to undertake an external pilot RCT (Best-BRA) with an embedded QuinteT Recruitment Intervention (QRI) to determine the feasibility of undertaking a trial comparing prepectoral and subpectoral techniques.Methods and analysisBest-BRA is a pragmatic, two-arm, external pilot RCT with an embedded QRI and economic scoping for resource use. Women who require a mastectomy for either breast cancer or risk reduction, elect to have an IBBR and are considered suitable for both prepectoral and subpectoral reconstruction will be recruited and randomised 1:1 between the techniques.The QRI will be implemented in two phases: phase 1, in which sources of recruitment difficulties are rapidly investigated to inform the delivery in phase 2 of tailored interventions to optimise recruitment of patients.Primary outcomes will be (1) recruitment of patients, (2) adherence to trial allocation and (3) outcome completion rates. Outcomes will be reviewed at 12 months to determine the feasibility of a definitive trial.Ethics and disseminationThe study has been approved by the National Health Service (NHS) Wales REC 6 (20/WA/0338). Findings will be presented at conferences and in peer-reviewed journals.Trial registration numberISRCTN10081873.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results