Publications by authors named "Nicola Jones"

252 Publications

The effect of person, treatment and prescriber characteristics on retention in opioid agonist treatment: a 15-year retrospective cohort study.

Addiction 2021 May 12. Epub 2021 May 12.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, NSW, Australia.

Background And Aims: There is limited evidence on the relationship between retention in opioid agonist treatment for opioid dependence and characteristics of treatment prescribers. This study estimated retention in buprenorphine and methadone treatment and its relationship with person, treatment and prescriber characteristics.

Design: Retrospective longitudinal study.

Setting: New South Wales, Australia.

Participants: People entering the opioid agonist treatment programme for the first time between August 2001 and December 2015.

Measurements: Time in opioid agonist treatment (primary outcome) was modelled using a generalized estimating equation model to estimate associations with person, treatment and prescriber characteristics.

Findings: The impact of medication type on opioid agonist treatment retention reduced over time; the risk of leaving treatment when on buprenorphine compared with methadone was higher among those who entered treatment earlier [e.g. 2001-03: odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.45-1.75] and lowest among those who entered most recently (2013-15: OR = 1.23, 95% CI = 1.11-1.36). In adjusted analyses, risk of leaving was reduced among people whose prescriber had longer tenure of prescribing (e.g. 3 versus 8 years: OR = 0.94, 95% CI = 0.93-0.95) compared with prescribers with shorter tenure. Aboriginal and Torres Strait Islander people, being of younger age, past-year psychosis disorder and having been convicted of more criminal charges in the year prior to treatment entry were associated with increased risk of leaving treatment.

Conclusion: In New South Wales, Australia, retention in buprenorphine treatment for opioid dependence, compared with methadone, has improved over time since its introduction in 2001. Opioid agonist treatment retention is affected not only by characteristics of the person and his or her treatment, but also of the prescriber, with those of longer prescribing tenure associated with increased retention of people in opioid agonist treatment.
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http://dx.doi.org/10.1111/add.15514DOI Listing
May 2021

Development of the patient-oriented research curriculum in child health (PORCCH).

Res Involv Engagem 2021 May 10;7(1):27. Epub 2021 May 10.

SickKids Research Institute, Hospital for Sick Children, Toronto, Canada.

Background: The Canadian Institutes for Health Research launched a national 'Strategy for Patient-Oriented Research' (SPOR) in 2011. Patient-oriented research is defined as a continuum of research that engages patients as partners, focuses on patient-identified priorities, and improves patient outcomes. Capacity development is a core element of SPOR. Barriers to patient-oriented research include unfamiliarity with the research process for patients and families and unfamiliarity with the methods of patient and family engagement for researchers.

Methods: The aim of the Patient-Oriented Research Curriculum in Child Health (PORCCH) is to build capacity in patient-oriented research in child health among patients and families, researchers, healthcare professionals, decision-makers, and trainees through a curriculum delivered via a series of interactive online modules (e-learning). A multi-disciplinary, multi-stakeholder steering committee, which included patients and families, guided the development of the curriculum and provided feedback on individual modules. The content, design, and development of each module were co-led by a parent and researcher in an equal partnership.

Results: PORCCH consists of a series of five modules. All modules are interactive and include video vignettes and knowledge comprehension questions. Access to the modules is free and each module takes approximately 30 min to complete. The five modules are: Research 101 (an Introduction to Patient-Oriented Research, parts 1 and 2), Patient Engagement 101 (an Introduction to Patient Engagement in Child Health Research, parts 1 and 2), and Research Ethics 101.

Conclusions: PORCCH was developed specifically to overcome recognized barriers to the engagement of patients and families in child health research. The aim of the curriculum is to build capacity in patient-oriented research in child health. The goal is for PORCCH to be a useful resource for all stakeholders involved in patient-oriented research: patients and families, researchers, healthcare professionals, decision-makers, and trainees.
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http://dx.doi.org/10.1186/s40900-021-00276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111753PMC
May 2021

Fermented foods: availability, cost, ingredients, nutritional content and on-pack claims.

J Hum Nutr Diet 2021 Apr 23. Epub 2021 Apr 23.

King's College London, Department of Nutritional Sciences, London, United Kingdom.

Introduction: Fermented foods have been consumed for millennia and commercially-produced variants are now available in the food supply. The aim was to investigate the availability, cost, ingredients, nutritional content and on-pack claims of commercially-available fermented foods in the United Kingdom (UK).

Methods: All products from seven categories of commercially-available fermented foods were systematically identified at eight national supermarket chains in the UK. Data were extracted from manufacturer and retailer websites and were compared between categories using Kruskal-Wallis test and Fisher's exact test.

Results: A total of 143 fermented foods were identified, with kombucha (41, 28.7%), kefir drinks (32, 22.4%), sauerkraut (22, 15.4%) and kefir yoghurts (21, 14.7%) being most common. The number of products sold at each retailer differed between categories (P=0.016), and was greatest for kefir drink (median 7.0, IQR 9.0), kombucha (5.5, 11.5) and kefir yoghurts (5.0, 8.5). Kombucha (£1.99/serving) and kefir drinks (£1.26/serving) were the most expensive fermented foods and sauerkraut (£0.66/serving) and miso (£0.20/serving) the least expensive. Energy, fat, saturated fat, sugar, protein and salt content varied between fermented foods (P<0.001). Nutrition claims were made on 72 (50.3%) products, the total number of cultures was labelled on 29 (20.3%), specific strains were named on 53 (37.1%) and bacteria-related benefits were promoted on 39 (27.3%) products.

Conclusions: Commercially-produced fermented foods are widely available in the UK, but are diverse in their cost, nutritional content, ingredients and use of on-pack claims. Consumers should be aware of these variations given limited evidence of functional benefits from controlled human trials.
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http://dx.doi.org/10.1111/jhn.12905DOI Listing
April 2021

Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine.

NPJ Vaccines 2021 Mar 29;6(1):43. Epub 2021 Mar 29.

National Infection Service, Public Health England, Porton Down, Wiltshire, UK.

Live attenuated influenza vaccine (LAIV) is widely used to protect humans from seasonal influenza infection, particularly in children. In contrast to inactivated vaccines, the LAIV can induce both mucosal and cellular immune responses. Here we show that a single dose of monovalent H1N1pdm09-specific LAIV in the ferret model is fully protective against a subsequent wild-type H1N1pdm09 challenge, and furthermore reduces the severity of disease following challenge with a different influenza A subtype (H3N2). The reduced severity comprised reductions in weight loss and fever, as well as more rapid clearance of virus, compared to non-vaccinated H3N2-challenged ferrets. No H3N2-neutralizing antibodies were detected in vaccinated ferret sera. Rather, heterosubtypic protection correlated with interferon-gamma+ (IFN-γ+) T-cell responses measured in peripheral blood and in lung lymphocytes. The IFN-γ+ cells were cross-reactive to H3N2 virus even when obtained from vaccinated animals that had never been exposed to H3N2 virus. We believe this study provides compelling evidence that the LAIV can provide a significant reduction in infection and symptoms when challenged with heterosubtypic influenza strains not included in the LAIV, highlighting the importance of cross-reactive T-cells in the design of a universal influenza vaccine.
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http://dx.doi.org/10.1038/s41541-021-00306-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007727PMC
March 2021

Cefazolin as second line treatment for invasive Methicillin-Susceptible Staphylococcus aureus infection in a UK cohort of patients.

J Infect 2021 May 3;82(5):e25-e27. Epub 2021 Feb 3.

Microbiology and Infectious Diseases Department, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.01.024DOI Listing
May 2021

COVID-19 patient with coronary thrombosis supported with ECMO and Impella 5.0 ventricular assist device: a case report.

Eur Heart J Case Rep 2020 Dec 20;4(6):1-6. Epub 2020 Nov 20.

Royal Papworth Hospital, Cambridge CB2 0AY, UK.

Background: COVID-19 can present with cardiovascular complications.

Case Summary: We present a case report of a 43-year-old previously fit patient who suffered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with thrombosis of the coronary arteries causing acute myocardial infarction. These were treated with coronary stenting during which the patient suffered cardiac arrest. He was supported with automated chest compressions followed by peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO). No immediate recovery of the myocardial function was observed and, after insufficient venting of the left ventricle was diagnosed, an Impella 5 pump was implanted. The cardiovascular function recovered sufficiently and ECMO was explanted and inotropic infusions discontinued. Due to SARS-CoV-2 pulmonary infection, hypoxia became resistant to conventional mechanical ventilation and the patient was nursed prone overnight. After initial recovery of respiratory function, the patient received a tracheostomy and was allowed to wake up. Following a short period of agitation his neurological function recovered completely. During the third week of recovery, progressive multisystem dysfunction, possibly related to COVID-19, developed into multiorgan failure, and the patient died.

Discussion: We believe that this is the first case report of coronary thrombosis related to COVID-19. Despite the negative outcome in this patient, we suggest that complex patients may in the future benefit from advanced cardiovascular support, and may even be nursed safely in the prone position with Impella devices.
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http://dx.doi.org/10.1093/ehjcr/ytaa342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717226PMC
December 2020

Retention of opioid agonist treatment prescribers across New South Wales, Australia, 2001-2018: Implications for treatment systems and potential impact on client outcomes.

Drug Alcohol Depend 2021 02 19;219:108464. Epub 2020 Dec 19.

National Drug and Alcohol Research Centre, University of NSW, Sydney NSW 2052, Australia. Electronic address:

Background: There has been much research on the efficacy and effectiveness of opioid agonist treatment (OAT), but less on its implementation and sustainability. A challenge internationally has been recruiting and retaining prescribers. This paper aims to characterise the prescribers in terms of OAT prescribing behaviours.

Methods: Retrospective cohort study in New South Wales, Australia. Participants were 2199 OAT prescribers between 1 st August 2001-19th September 2018.We examined trends in initiation and cessation of OAT prescribers. Adjusted hazard ratios were calculated to estimate prescriber retention, adjusting for year of initiation, practice type, client load and treatment prescribed.

Results: The rate of prescribers ceasing OAT prescribing has been increasing over time: a prescriber who initiated between 2016-2017 had over four times the risk of cessation compared with one who initiated before 2001, AHR: 4.77; [3.67-6.21]. The highest prescriber cessation rate was in prescribers who had prescribed for shorter time periods. The annual percentage of prescribers who ceased prescribing among those who prescribed for ≤5 years increased from 3% in 2001 to 20 % in 2017. By 2017 more prescribers were discontinuing prescribing than new prescribers were starting. Approximately 87 % (n = 25,167) of OAT clients were under the care of 20 % of OAT prescribers (n = 202); half had been prescribing OAT for 17+ years.

Conclusions: OAT prescribing is increasingly concentrated in a small group of mature prescribers, and new prescribers are not being retained. There is a need to identify and respond to the reasons that contribute to newer prescribers to cease prescribing and put in place strategies to increase retention and broaden the base of doctors involved in such prescribing.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855715PMC
February 2021

How COVID-19 is changing the cold and flu season.

Authors:
Nicola Jones

Nature 2020 12;588(7838):388-390

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http://dx.doi.org/10.1038/d41586-020-03519-3DOI Listing
December 2020

Burning behaviour of rainscreen façades.

J Hazard Mater 2021 02 9;403:123894. Epub 2020 Sep 9.

Centre for Fire and Hazard Science, University of Central Lancashire, Preston, PR1 2HE, UK. Electronic address:

Four reduced-height (5 m) BS 8414-1 façade flammability tests were conducted, three having mineral-filled aluminium composite material (ACM-A2) with polyisocyanurate (PIR) and phenolic (PF) foam and stone wool (SW) insulation, the fourth having polyethylene-filled ACM (ACM-PE) with PIR insulation. Each façade was constructed from a commercial façade engineer's design, and built by practising façade installers. The ACM-PE/PIR façade burnt so ferociously it was extinguished after 13.5 min, for safety. The three ACM-A2 cladding panels lost their structural integrity, and melted away from the test wall, whereupon around 40% of both the combustible PIR and PF insulation burnt and contributed to the fire spread. This demonstrates why all façade products must be non-combustible, not just the outer panels. For the three ACM-A2 tests, while the temperature in front of the cavity was independent of the insulation, the temperatures within it varied greatly, depending on the insulation. The system using PF/A2 allowed fire to break through to the cavity first, as seen by a sharp increase in temperature after 17 min. For PIR/A2, the temperature increased sharply at 22 minutes, as the panel started to fall away from the wall. For SW/A2, no rapid temperature rise was observed.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123894DOI Listing
February 2021

Intersecting Vulnerabilities: The Impacts of COVID-19 on the Psycho-emotional Lives of Young People in Low- and Middle-Income Countries.

Eur J Dev Res 2020 Nov 9:1-26. Epub 2020 Nov 9.

GAGE Lebanon, Beirut, Lebanon.

Across diverse contexts, emerging evidence suggests that the COVID-19 pandemic is increasing levels of anxiety and stress. In calling for greater attention to people's psychosocial and emotional well-being, global actors have paid insufficient attention to the realities of the pandemic in low- and middle-income countries, where millions of people are already exposed to intersecting vulnerabilities. Chronic poverty, protracted violence, conflict and displacement, coupled with weak health, education and protection systems, provide the backdrop of many adolescents' lives. Drawing on qualitative in-country telephone interviews with over 500 adolescents in Ethiopia, Côte d'Ivoire and Lebanon, this article unpacks the age and gendered dimensions of COVID-19 and its response. We conclude by discussing the implications for COVID-19 recovery efforts, arguing that embedding adolescent-centred, inclusive approaches in education, community-based health and social protection responses, has the potential to mitigate the psycho-emotional toll of the pandemic on young people and promote resilience.
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http://dx.doi.org/10.1057/s41287-020-00325-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649704PMC
November 2020

Risk of discharge against medical advice among hospital inpatients with a history of opioid agonist therapy in New South Wales, Australia: A cohort study and nested crossover-cohort analysis.

Drug Alcohol Depend 2020 12 12;217:108343. Epub 2020 Oct 12.

National Drug and Alcohol Research Centre, 22-32 King St, Randwick NSW 2031, Australia.

Background: People who use illicit opioids have high rates of hospital admission. We aimed to measure the risk of discharge against medical advice among inpatients with a history of opioid agonist therapy (OAT), and test whether OAT is associated with lower risk of discharge against medical advice.

Methods: We conducted a cohort study of patients admitted to hospital in an emergency between 1 August 2001 and 30 April 2018 in New South Wales, Australia. All patients had a previous episode of OAT in the community. The main outcome was discharge against medical advice, and the main exposure was whether patients had an active OAT permit at the time of admission.

Results: 14,035/116,957 admissions (12 %) ended in discharge against medical advice. Admissions during periods of OAT had 0.79 (0.76-0.83; p < 0.001) times the risk of discharge against medical advice, corresponding to an absolute risk reduction of 3.0 percentage points. Risk of discharge against medical advice was higher among patients who were younger, male, identified as Aboriginal and/or Torres Strait Islander, and those admitted for accidents, drug-related reasons, or injecting-related injuries (such as cutaneous abscesses). In a subsample of 7793 patients included in a crossover-cohort analysis, OAT was associated with 0.84 (95 % CI 0.76-0.93; p < 0.001) times the risk of discharge against medical advice.

Conclusions: Among patients with a history of OAT, one in eight emergency hospital admissions ends in discharge against medical advice. OAT enrolment at the time of admission is associated with a reduction of this risk.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736124PMC
December 2020

Hospitalisations for non-fatal overdose among people with a history of opioid dependence in New South Wales, Australia, 2001-2018: Findings from the OATS retrospective cohort study.

Drug Alcohol Depend 2021 01 18;218:108354. Epub 2020 Oct 18.

National Drug and Alcohol Research Centre, University of NSW, Sydney, NSW, 2052, Australia. Electronic address:

Background: To examine, among a cohort of opioid dependent people with a history of opioid agonist treatment (OAT), the frequency and incidence rates of non-fatal overdose (NFOD) hospital separations over time, by age and sex.

Methods: Retrospective cohort study of people with a history of OAT using state-wide linked New South Wales (NSW) data. The incidence of NFOD hospital separations involving an opioid, sedative, stimulant or alcohol was defined according to the singular or combination of poisoning/toxic effect using ICD-10-AM codes. Crude incidence rates were calculated by gender, age group and calendar year.

Results: There were 31.8 (31.3-32.3) NFOD per 1,000 person-years (PY). Opioid NFOD incidence was higher in women than men: incidence rate ratio (IRR) 1.11 per 1,000PY; 95 %CI: [1.06-1.17]; women had higher sedative NFOD rates than men, IRR 1.27 per 1,000PY [1.21-1.34]. Participants ≤25 years, 26-30yrs, and 31-35yrs had higher incidence of opioid NFOD compared to 46+yrs, with IRRs of: 1.45 per 1,000PY; [1.32-1.59]; 1.20 per 1,000PY; [1.11-1.30] and 1.22 per 1,000PY; [1.13-1.32], respectively. Between 2006-7 and 2016-17, the cohort accounted for 19 % of NSW opioid NFOD episodes, 12 % of sedative, 14 % of stimulant and 5 % of acute alcohol-related NFOD.

Conclusions: Hospital stays due to NFOD are a relatively frequent occurrence among opioid-dependent people. There are clear differences in rates and substances involved by sex, age and over time. Evidence-based interventions that prevent overdose among people who are opioid dependent need to be delivered to scale, including widespread community provision of naloxone.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108354DOI Listing
January 2021

Murine Model of Thermal Burn Injury for Evaluating Protein Therapeutics Derived from Viruses.

Methods Mol Biol 2021 ;2225:93-105

Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.

In vivo wound healing models are predictive preclinical tests for therapeutics that enhance skin repair or limit scarring. Large animals, such as swine, heal in a manner similar to humans, but testing is impractical and expensive. Experiments in mice are more economic, but may be less translatable as this species heals primarily through contraction, not by the processes of epithelialization and granulation tissue formation as seen in human wounds. Here, we describe a murine model of thermal burn injury that closely mimics human healing, resulting in a large, hypertrophic-like scar. This practical, reproducible model is ideal for testing promising wound-healing therapies, such as virus-derived growth factors and immune-modulatory proteins.
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http://dx.doi.org/10.1007/978-1-0716-1012-1_6DOI Listing
March 2021

Review: Helicobacter pylori infection in children.

Helicobacter 2020 Sep;25 Suppl 1:e12742

Departments of Paediatrics and Physiology, Division of Gastroenterology Hepatology and Nutrition, Cell Biology Program, SickKids Research Institute, University of Toronto, SickKids, Toronto, Canada.

Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy-based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post-eradication follow-up, was supported by the current literature.
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http://dx.doi.org/10.1111/hel.12742DOI Listing
September 2020

Life expectancy of people who are dependent on opioids: A cohort study in New South Wales, Australia.

J Psychiatr Res 2020 11 23;130:435-440. Epub 2020 Aug 23.

National Drug and Alcohol Research Centre, 22-32 King St, Randwick, NSW, 2031, Australia.

Background: People who are dependent on opioids have increased risk of premature death, but there are few estimates of life expectancy.

Methods: We calculated age-specific mortality rates in a cohort of people who had at least one prescription of an opioid agonist (methadone or buprenorphine) between 2001 and 2018 in New South Wales, Australia. We used life tables to estimate life expectancy at age 18. We also estimated the potential years of life lost before age 75, decomposed by cause of death.

Results: The cohort included 47,197 people, with a median of 9.8 years of follow-up. 5097 participants died, and the standardised mortality ratio (compared to the general population of New South Wales) was 6.06 (95% CI 5.90-6.23). Life expectancy at age 18 was an additional 47.5 years (95% CI 42.9-50.5) for men and 50.7 years (95% CI 45.4-54.8) for women; deficits of 14.7 and 15.8 years respectively when compared to the general population. The largest cause of death was non-communicable physical diseases, which accounted for 47% of deaths in life tables for men and 42% for women. Drug-related deaths accounted for 16% of deaths for men and 19% for women, but due to the young age at which these deaths occur, they contributed approximately one third of potential years of life lost.

Conclusion: In common with people with serious mental illnesses, people who are dependent on opioids have substantially reduced life expectancy. In both populations most excess deaths relate to non-communicable physical diseases.
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http://dx.doi.org/10.1016/j.jpsychires.2020.08.013DOI Listing
November 2020

Smoke toxicity of rainscreen façades.

J Hazard Mater 2021 02 14;403:123694. Epub 2020 Aug 14.

Centre for Fire and Hazard Science, University of Central Lancashire, Preston, PR1 2HE, UK. Electronic address:

The toxic smoke production of four rainscreen façade systems were compared during large-scale fire performance testing on a reduced height BS 8414 test wall. Systems comprising 'non-combustible' aluminium composite material (ACM) with polyisocyanurate (PIR), phenolic foam (PF) and stone wool (SW) insulation, and polyethylene-filled ACM with PIR insulation were tested. Smoke toxicity was measured by sampling gases at two points - the exhaust duct of the main test room and an additional 'kitchen vent', which connects the rainscreen cavity to an occupied area. Although the toxicity of the smoke was similar for the three insulation products with non-combustible ACM, the toxicity of the smoke flowing from the burning cavity through the kitchen vent was greater by factors of 40 and 17 for PIR and PF insulation respectively, when compared to SW. Occupants sheltering in a room connected to the vent are predicted to collapse, and then inhale a lethal concentration of asphyxiant gases. This is the first report quantifying fire conditions within the cavity and assessing smoke toxicity within a rainscreen façade cavity.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123694DOI Listing
February 2021

Differential occupational risks to healthcare workers from SARS-CoV-2 observed during a prospective observational study.

Elife 2020 08 21;9. Epub 2020 Aug 21.

Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45-6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99-3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07-2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28-0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25-2.21]) and Asian (1.51 [1.28-1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34-3.15]).
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http://dx.doi.org/10.7554/eLife.60675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486122PMC
August 2020

Gender-norms, violence and adolescence: Exploring how gender norms are associated with experiences of childhood violence among young adolescents in Ethiopia.

Glob Public Health 2020 Aug 6:1-14. Epub 2020 Aug 6.

Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.

Adolescence is a time of particular risk for violence perpetrated by parents, teachers, peers and intimate partners. Social norms that condone violent discipline, promote masculinities focused on violence, and support gender inequality play an important role in perpetuating violence. However, little is known about the relationship between inequitable gender norms and children's experiences of violence from parents or other adults in the household. Utilising data from the Gender and Adolescence: Global Evidence (GAGE) study, this paper explores how adolescent and household attitudes and community-level gender norms influence experiences of violence among young adolescents (aged 10-12) in Ethiopia. Our results show that community norms, rather than adolescent and household attitudes, are significantly associated with experiences of household violence. This result holds for boys and girls, and in rural areas. In urban areas, however, adolescent attitudes were more influential than community norms, perhaps indicating less cohesive communities. Overall, these findings suggest that violence prevention programming should prioritise shifting community norms, particularly in rural areas, in order to promote adolescent girls' and boys' right to bodily integrity.
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http://dx.doi.org/10.1080/17441692.2020.1801788DOI Listing
August 2020

Cortical cells are altered by factors including bone morphogenetic protein released from a placental barrier model under altered oxygenation.

Neuronal Signal 2020 Apr 9;4(1):NS20190148. Epub 2020 Apr 9.

School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, U.K.

Episodes of hypoxia and hypoxia/reoxygenation during foetal development have been associated with increased risk of neurodevelopmental conditions presenting in later life. The mechanism for this is not understood; however, several authors have suggested that the placenta plays an important role. Previously we found both placentas from a maternal hypoxia model and pre-eclamptic placentas from patients release factors lead to a loss of dendrite complexity in rodent neurons. Here to further explore the nature and origin of these secretions we exposed a simple model of the placental barrier, consisting of a barrier of human cytotrophoblasts, to hypoxia or hypoxia/reoxygenation. We then exposed cortical cultures from embryonic rat brains to the conditioned media (CM) from below these exposed barriers and examined changes in cell morphology, number, and receptor presentation. The barriers released factors that reduced dendrite and astrocyte process lengths, decreased GABAB1 staining, and increased astrocyte number. The changes in astrocytes required the presence of neurons and were prevented by inhibition of the SMAD pathway and by neutralising Bone Morphogenetic Proteins (BMPs) 2/4. Barriers exposed to hypoxia/reoxygenation also released factors that reduced dendrite lengths but increased GABAB1 staining. Both oxygen changes caused barriers to release factors that decreased GluN1, GABAAα1 staining and increased GluN3a staining. We find that hypoxia in particular will elicit the release of factors that increase astrocyte number and decrease process length as well as causing changes in the intensity of glutamate and GABA receptor staining. There is some evidence that BMPs are released and contribute to these changes.
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http://dx.doi.org/10.1042/NS20190148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363303PMC
April 2020

Intersecting inequalities, gender and adolescent health in Ethiopia.

Int J Equity Health 2020 06 15;19(1):97. Epub 2020 Jun 15.

Gender and Adolescence: Global Evidence Research Programme and Department of Economics, University of Oklahoma, Norman, USA.

Background: Until recently, global public health initiatives have tended to overlook the ways that social factors shape adolescent health, and particularly how these dynamics affect the specific needs of adolescents in relation to information about puberty, menstruation and sexual health. This article draws on mixed methods data from rural and urban areas of Ethiopia to explore how access to health information and resources - and subsequently health outcomes - for adolescents are mediated by gender and age norms, living in different geographical locations, poverty, disability and migration.

Methods: Data was collected in 2017-2018 for the Gender and Adolescence: Global Evidence (GAGE) mixed-methods longitudinal research baseline in three regions of Ethiopia (Afar, Amhara and Oromia). Quantitative data was collected from over 6800 adolescents and their caregivers, with qualitative data obtained from a sub-sample of 220 adolescents, their families and communities. Adolescent participants shared their experiences of health, illness and nutrition over the previous year; their knowledge and sources of information about sexual and reproductive health and puberty; and their attitudes toward sexual and reproductive health. Regression analysis was used to explore differences by gender, age, rural/urban residence, and disability status, across a set of adolescents' health knowledge and other outcomes in the quantitative data. Intersectional analysis was used in analysing the qualitative data.

Results: Analysis suggested that gender inequality intersects with age, disability and rural/urban differences to shape young people's access to information about puberty, with knowledge about this topic particularly lacking amongst younger adolescents in rural areas. Drought and lack of access to clean water exacerbates health challenges for adolescents in rural areas, where a lack of information and absence of access to preventive healthcare services can lead to permanent disability. The research also found that gaps in both school-based and alternative sources of education about puberty and menstruation reinforce stigma and misinformation, especially in rural areas where adolescents have higher school attrition rates. Gendered cultural norms that place high value on marriage and motherhood generate barriers to contraceptive use, particularly in certain rural communities.

Conclusions: As they progress through adolescence, young people's overall health and access to information about their changing bodies is heavily shaped by intersecting social identities. Structural disadvantages such as poverty, distress migration and differential access to healthcare intersect with gender norms to generate further inequalities in adolescent girls' and boys' health outcomes.
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http://dx.doi.org/10.1186/s12939-020-01214-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296636PMC
June 2020

How coronavirus lockdowns stopped flu in its tracks.

Authors:
Nicola Jones

Nature 2020 May 21. Epub 2020 May 21.

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http://dx.doi.org/10.1038/d41586-020-01538-8DOI Listing
May 2020

Orf Virus IL-10 and VEGF-E Act Synergistically to Enhance Healing of Cutaneous Wounds in Mice.

J Clin Med 2020 Apr 11;9(4). Epub 2020 Apr 11.

Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.

Orf virus (OV) is a zoonotic parapoxvirus that causes highly proliferative skin lesions which resolve with minimal inflammation and scarring. OV encodes two immunomodulators, vascular endothelial growth factor (VEGF)-E and interleukin-10 (ovIL-10), which individually modulate skin repair and inflammation. This study examined the effects of the VEGF-E and ovIL-10 combination on healing processes in a murine wound model. Treatments with viral proteins, individually and in combination, were compared to a mammalian VEGF-A and IL-10 combination. Wound biopsies were harvested to measure re-epithelialisation and scarring (histology), inflammation, fibrosis and angiogenesis (immunofluorescence), and gene expression (quantitative polymerase chain reaction). VEGF-E and ovIL-10 showed additive effects on wound closure and re-epithelialisation, and suppressed M1 macrophage and myofibroblast infiltration, while allowing M2 macrophage recruitment. The viral combination also increased endothelial cell density and pericyte coverage, and improved collagen deposition while reducing the scar area. The mammalian combination showed equivalent effects on wound closure, re-epithelialisation and fibrosis, but did not promote blood vessel stabilisation or collagen remodeling. The combination treatments also differentially altered the expression of transforming growth factor beta isoforms, and These findings show that the OV proteins synergistically enhance skin repair, and act in a complimentary fashion to improve scar quality.
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http://dx.doi.org/10.3390/jcm9041085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231296PMC
April 2020

Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the 'review and revise' experience.

Pilot Feasibility Stud 2020 4;6:43. Epub 2020 Apr 4.

1Centre for Clinical and Community Applications of Health Psychology, University of Southampton, Southampton, UK.

Background: We aimed to investigate and optimise the acceptability and usefulness of a patient leaflet about antibiotic prescribing decisions made during hospitalisation, and to explore individual patient experiences and preferences regarding the process of antibiotic prescription 'review and revise' which is a key strategy to minimise antibiotic overuse in hospitals.

Methods: In this qualitative study, run within the feasibility study of a large, cluster-randomised stepped wedge trial of 36 hospital organisations, a series of semi-structured, think-aloud telephone interviews were conducted and data were analysed using thematic analysis. Fifteen adult patients who had experienced a recent acute medical hospital admission during which they had been prescribed antimicrobials and offered a patient leaflet about antibiotic prescribing were recruited to the study.

Results: Participants reacted positively to the leaflet, reporting that it was both an accessible and important source of information which struck the appropriate balance between informing and reassuring. Participants all valued open communication with clinicians, and were keen to be involved in antibiotic prescribing decisions, with individuals reporting positive experiences regarding antibiotic prescription changes or stopping. Many participants had prior experience or knowledge of antibiotics and resistance, and generally welcomed efforts to reduce antibiotic usage. Overall, there was a feeling that healthcare professionals (HCPs) are trusted experts providing the most appropriate treatment for individual patient conditions.

Conclusions: This study offers novel insights into how patients within secondary care are likely to respond to messages advocating a reduction in the use of antibiotics through the 'review and revise' approach. Due to the level of trust that patients place in their care provider, encouraging HCPs within secondary care to engage patients with greater communication and information provision could provide great advantages in the drive to reduce antibiotic use. It may also be beneficial for HCPs to view patient experiences as cumulative events that have the potential to impact future behaviour around antibiotic use. Finally, pre-testing messages about antibiotic prescribing and resistance is vital to dispelling any misconceptions either around effectiveness of treatment for patients, or perceptions of how messages may be received.

Trial Registration: Current Controlled Trials ISRCTN12674243 (10 April 2017).
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http://dx.doi.org/10.1186/s40814-020-00590-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126355PMC
April 2020

Microbial aetiology of brain abscess in a UK cohort: Prominent role of Streptococcus intermedius.

J Infect 2020 06 13;80(6):623-629. Epub 2020 Mar 13.

Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; NIHR Oxford British Research Council (BRC), John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Electronic address:

Background: Brain abscess is an uncommon condition, but carries high mortality. Current treatment guidelines are based on limited data. Surveillance of clinical, radiological and microbiology data is important to inform patient stratification, interventions, and antimicrobial stewardship.

Methods: We undertook a retrospective, observational study of patients with brain abscess, based on hospital coding, in a UK tertiary referral teaching hospital. We reviewed imaging data, laboratory microbiology, and antibiotic prescriptions.

Results: Over a 47 month period, we identified 47 adults with bacterial brain abscess (77% male, median age 47 years). Most of the abscesses were solitary frontal or parietal lesions. A microbiological diagnosis was secured in 39/47 (83%) of cases, among which the majority were of the Streptococcus milleri group (27/39; 69%), with a predominance of Streptococcus intermedius (19/27; 70%). Patients received a median of 6 weeks of intravenous antibiotics (most commonly ceftriaxone), with variable oral follow-on regimens. Ten patients (21%) died, up to 146 days after diagnosis. Mortality was significantly associated with increasing age, multiple abscesses, immunosuppression and the presence of an underlying cardiac anomaly.

Conclusion: Our data suggest that there has been a shift away from staphylococcal brain abscesses, towards S. intermedius as a dominant pathogen. In our setting, empiric current first line therapy with ceftriaxone remains appropriate on microbiological grounds and narrower spectrum therapy may sometimes be justified. Mortality of this condition remains high among patients with comorbidity. Prospective studies are required to inform optimum dose, route and duration of antimicrobial therapy.
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http://dx.doi.org/10.1016/j.jinf.2020.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267774PMC
June 2020

Do restrictive gender attitudes and norms influence physical and mental health during very young Adolescence? Evidence from Bangladesh and Ethiopia.

SSM Popul Health 2019 Dec 20;9:100480. Epub 2019 Nov 20.

Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, D.C, 20052, USA.

Adolescence is seen as a window of opportunity for intervention but also as a time during which restrictive gender attitudes and norms become more salient. This increasingly gendered world has the potential to profoundly influence adolescents' capabilities, including their physical and mental health. Using quantitative data on 6,500 young adolescents (10-12) from the Gender and Adolescence: Global Evidence (GAGE) program, this paper analyses the association between restrictive gender attitudes (RGAs) at the individual level and restrictive gender norms (RGNs) at the community level and physical and mental health in Bangladesh and Ethiopia. We find significant associations between RGAs and RGNs and height-for-age z-scores, body mass index z-scores, self-reported health, adolescent hunger, psychological well-being, and self-esteem. We find no relationship between RGAs or RGNs and illness. We also find heterogeneity across country and urbanicity. We find surprisingly limited variation by gender, and the differences we do see point to important vulnerabilities for both boys and girls. Our results point to the powerful role that distal factors such as culture and beliefs, as manifested through RGAs and RGNs, can play in shaping health outcomes for both boys and girls and suggest important next steps for future research and policy.
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http://dx.doi.org/10.1016/j.ssmph.2019.100480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978471PMC
December 2019

2019 Harry Shwachman Award: Dr Anne M. Griffiths, MD, FRCPC.

J Pediatr Gastroenterol Nutr 2020 04;70(4):405

Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1097/MPG.0000000000002606DOI Listing
April 2020

MCOLN1/TRPML1 inhibition - a novel strategy used by to escape autophagic killing and antibiotic eradication therapy .

Autophagy 2020 01 13;16(1):169-170. Epub 2019 Oct 13.

Cell Biology Program.

Inhibition of host macroautophagy/autophagy is one of the strategies used by several intracellular pathogens, including , to escape killing. Here we discuss our recent work that revealed the novel mechanism by which the vacuolating cytotoxin A (VacA) produced by inhibits lysosomal and autophagic killing. We discovered that VacA impairs the activity of the lysosomal calcium channel MCOLN1/TRPML1 leading to the formation of enlarged, dysfunctional lysosomes and autophagosomes that serve as an intracellular niche, which allows the bacteria to escape eradication therapy.
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http://dx.doi.org/10.1080/15548627.2019.1677322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984606PMC
January 2020