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1.
PLoS Global Public Health ; 2(4), 2022.
Article in English | CAB Abstracts | ID: covidwho-1854976

ABSTRACT

It is unclear whether the literature on adolescent gender dysphoria (GD) provides sufficient evidence to inform clinical decision making adequately. In the second of a series of three papers, we sought to review published evidence systematically regarding the extent and nature of mental health problems recorded in adolescents presenting for clinical intervention for GD. Having searched PROSPERO and the Cochrane library for existing systematic reviews (and finding none), we searched Ovid Medline 1946-October week 4 2020, Embase 1947-present (updated daily), CINAHL 1983-2020, and PsycInfo 1914-2020. The final search was carried out on the 2nd November 2020 using a core strategy including search terms for 'adolescence' and 'gender dysphoria' which was adapted according to the structure of each database. Papers were excluded if they did not clearly report on clinically-likely gender dysphoria, if they were focused on adult populations, if they did not include original data (epidemiological, clinical, or survey) on adolescents (aged at least 12 and under 18 years), or if they were not peer-reviewed journal publications. From 6202 potentially relevant articles (post deduplication), 32 papers from 11 countries representing between 3000 and 4000 participants were included in our final sample. Most studies were observational cohort studies, usually using retrospective record review (21). A few compared cohorts to normative or population datasets;most (27) were published in the past 5 years. There was significant overlap of study samples (accounted for in our quantitative synthesis). All papers were rated by two reviewers using the Crowe Critical Appraisal Tool v1.4 (CCAT). The CCAT quality ratings ranged from 45% to 96%, with a mean of 81%. More than a third of the included studies emerged from two treatment centres: there was considerable sample overlap and it is unclear how representative these are of the adolescent GD community more broadly. Adolescents presenting for GD intervention experience a high rate of mental health problems, but study findings were diverse. Researchers and clinicians need to work together to improve the quality of assessment and research, not least in making studies more inclusive and ensuring long-term follow-up regardless of treatment uptake. Whole population studies using administrative datasets reporting on GD/gender non-conformity may be necessary, along with inter-disciplinary research evaluating the lived experience of adolescents with GD.

2.
Journal of Virology ; 96(4):16, 2022.
Article in English | Web of Science | ID: covidwho-1755961

ABSTRACT

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not ex-hibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited antiviral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, similar to 50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-lambda and Tnf-alpha) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Micro-glia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work dem-onstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

3.
Developmental Medicine and Child Neurology ; 64(SUPPL 1):24-25, 2022.
Article in English | EMBASE | ID: covidwho-1723125

ABSTRACT

Background: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS) causes prolonged hospitalisation and morbidity. The longer term neurological and health outcomes in children following PIMS-TS are largely unknown. Methods: In this single-institution study, we evaluated the domains of daily living, physical, emotional, and quality of life outcomes at 6 months following PIMS-TS. Data were collected by telephone questionnaire interviews with parents and children and also using standardized assessment tools -PedsQL-Multidimensional Fatigue Scale, and Paediatric Symptom Checklist (PSC). Results: Data were obtained from 81 children admitted with PIMS-TS between April and August 2020. 49 were males (60%) and 52 (63%) non-white. Median age was 9 years (8-17 years) with length of stay of 6 days (range 1-22 days). Prior to discharge, 34 children (42%) had difficulties with activities of daily living whereas only 5 (6%) persisted on 6 months follow up. Exercise intolerance/mobility difficulty was observed in 40 children (9%) at discharge compared to 20 (25%) 6 months later. Predictors associated with difficulty in exercise tolerance/mobility were obesity (OR=4.0;95% CI: 1.1-13.7;p=0.03) and older age (OR=1.1;95% CI: 0.99-1.3;p=0.086). Inflammatory markers on admission (CRP, fibrinogen, D-dimer and ferritin) did not correlate with worse outcome at follow-up nor did sex and length of stay. The PedsQL-Multidimensional Fatigue Scale revealed a median score of 94 (IQR: 83-100) indicating an overall average range quality of life. The PSC were in line with population prevalence of behavioural/emotional difficulties: 10% had difficulties with attention;7% and 4% of patients had internalizing and externalizing difficulties, respectively Conclusion: Overall, patients with PIMS-TS have good short-term outcomes at 6 months with respect to daily functioning, quality of life, and behaviour. One in four had some difficulty with mobility/pain requiring rehabilitation, with main risk factors being obesity and older age. Further studies are required to evaluate long-term sequelae.

4.
6.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293060

ABSTRACT

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ~50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine ( Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19 ) and cytokine ( Ifn-lambda and Tnf-alpha ) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. Importance: Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

7.
African Journal of Health Professions Education ; 13:4-5, 2021.
Article in English | Africa Wide Information | ID: covidwho-1320678

ABSTRACT

AFRICAN DEVELOPMENT Abstract: The COVID-19 pandemic has resulted in an upheaval in health sciences education. Globally, training of medical students on university campuses and clinical platforms was suspended and rapidly transitioned to online learning. In some countries, graduation of senior medical students was expedited in order to contribute to a health workforce in crisis. The transition to online learning has been particularly challenging in low- and middle-income countries where access to remote learning opportunities is limited for some students and further widens societal inequities. The pandemic, however, also provides an opportunity to re-imagine clinical learning and develop innovative ways to strengthen the clinical training platform and health system

8.
Thorax ; 76(SUPPL 1):A144-A145, 2021.
Article in English | EMBASE | ID: covidwho-1146446

ABSTRACT

Introduction: Mepolizumab is a biologic agent targeting interleukin (IL)-5 which is currently licensed as add-on therapy for severe eosinophilic asthmatic (SEA). It is usually administered in a hospital setting but with the option of homecare being introduced in 2019, the 4-weekly subcutaneous injections can be self-administered at home. We investigated whether there was a change in asthma control following the transition to home administration and whether a differential response to treatment exists following transition to homecare before and after the onset of the COVID-19 pandemic. Methods: Patients receiving mepolizumab via home care were stratified according to those who had a planned transition to homecare prior to 1st Feb 2020 versus those who had an unplanned transition after this date necessitated by the COVID-19 pandemic. The last Asthma Control Questionnaire-6 (ACQ6) measured in clinic ('baseline') was compared with that collected by telephone consultation 6-8 weeks after transition ('homecare'). Patients were excluded if both values were not available. Results: Of 87 mepolizumab patients included in the analysis, 46 were planned transitions. There was no significant (Figure presented) difference in the pre-biologic ACQ6 (p=0.07) between groups. Immediately prior to transition to homecare (baseline), the planned group had a lower mean ACQ6 than those in the unplanned group (1.19 vs 1.90, P=0.004). The ACQ6 on homecare decreased significantly in both groups (-0.47 in the planned group vs -0.56 in the unplanned group, both P<0.001). The ACQ6 for the planned cohort during homecare was significantly lower than that for the unplanned group (0.72 vs 1.34, P=0.012) (figure 1). (Table presented) Conclusions: We found a significant improvement in ACQ6 for all SEA patients established on Mepolizumab who transitioned to home mepolizumab administration. This improvement occurred irrespective of whether the transition was 'planned' or 'unplanned'. Further research is required to understand the potential influence of shielding during lockdown and the method of ACQ assessment (telephone vs face-to-face ACQ reporting in clinic) on this improvement.

9.
Thorax ; 76(SUPPL 1):A144, 2021.
Article in English | EMBASE | ID: covidwho-1146445

ABSTRACT

Introduction: The COVID-19 pandemic necessitated the rapid transition of large numbers of patients onto homecare to facilitate on-going therapy in a cohort of patients who were 'shielding'. Alongside this, patients continued to need to be initiated on biologic therapy in spite of the pandemic. The impact of administering biologic therapy at home is largely unknown, yet crucial to optimise patient outcome and minimise steroid burden. We investigated whether there was a differential response following transition to homecare of established patients versus those newly started. Methods: Patients with severe eosinophilic asthma receiving home benralizumab were stratified according to those who had received ≥3 doses prior to COVID-19 lockdown on the 15th March 2020 ('established' patients) versus those who were initiated after this date ('new' patients). We compared the last Asthma Control Questionnaire-6 (ACQ6) measured in clinic with that collected by telephone consultation 8-12 weeks after transition to homecare. Patients were excluded if both values were not available. Results: 246 benralizumab patients were included in the analysis, of whom 49 (20%) were new. There was no significant difference in pre-biologic ACQ6, pre-homecare (baseline) (Figure presented) ACQ6 or post-homecare ACQ6 between the new and established patient groups. Both cohorts exhibited a similar magnitude of improvement in their ACQ6 following the transition to homecare (-0.73 in the established group vs -0.73 in the new group, both P<0.0001) (figure 1). Conclusions: We have demonstrated that early transition to homecare in patients treated with benralizumab is not associated with worse clinical outcomes as assessed by ACQ6. The improvements in ACQ6 were seen irrespective of whether they were 'established' on therapy at time of transition or 'new'. Further research is required to understand the potential influence of lockdown and/or telephone vs face-to-face ACQ reporting.

10.
Mind and Society ; 2021.
Article in English | Scopus | ID: covidwho-1092027

ABSTRACT

This author offers of narrative of hope in response to the coronavirus pandemic by viewing it as a wake-up call to lean into the adaptive moral challenge of stewardship for the future of humanity and the planet. Acknowledging the many material and social benefits of a global regime of free market urbanism built on advances in science and technology, this is a point in geohistory, the Anthropocene, when the impact of human activities on the Earth has begun to outcompete natural processes. The coronavirus has illuminated systemic moral failures and new moral challenges of the Anthropocene that call for adaptive response if we are to build a hopeful future for humanity and the planet. Pointing to millennia of human adaptive response to threats and disasters, the author asserts an evolutionary hardiness attributable as much to moral capacities as rational intelligence as a singularly defining trait fueling millennia of human adaptive learning and thrival. The current pandemic is the latest point in humanity’s moral evolution of adaptive response to moments of urgent threat that have tested, expanded, and defined our character and moral capacities as a species. Rather than falter under the moral burden of the coronavirus threat and its consequences, the author views this pivotal point as an opportunity to stretch human moral horizons by taking responsibility for the urgent moral challenges we have created and inventing new ethical frameworks and tools that will lead us to new moral understandings and solutions to the moral challenges we face. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

11.
Journal of Molecular Diagnostics ; 22(11):S42-S42, 2020.
Article in English | Web of Science | ID: covidwho-1070278
13.
Pubmed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-2560

ABSTRACT

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk. OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize integrity of reseach aims while minimizing infection risk based on the latest understanding of the virus. METHODS: We drew on a combination of expert consultations, risk assessment frameworks, institutional guidance and literature to develop our framework. We then systematically graded clinical, behavioral, laboratory and field environmental health research activities in four countries for both adult and child subjects using this framework. RESULTS: Our framework assesses risk based on staff proximity to the participant, exposure time between staff and participants, and potential aerosolization while performing the activity. One of of four risk levels, from minimal to unacceptable, is assigned and guidance on protective measures is provided. Those activities which can potentially aerosolize the virus are deemed the highest risk. CONCLUSIONS: By applying a systematic, procedure-specific approach to risk assessment for each trial activity, we can compare trial activities using the same criteria. This approach allows us to protect our participants and research team and to uphold our ability to deliver on the research commitments we have made to our participants, local communities, and funders. The trial is registered with clinicaltrials.gov (NCT02944682).

14.
In Practice ; 42(6):361-364, 2020.
Article in English | EMBASE | ID: covidwho-722669

ABSTRACT

Covid-19 has had an impact on everyone in extremely different ways;understanding this, and subsequently approaching everyone's challenges individually, is the starting point to getting your team back on track.

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