Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Wellcome Open Res ; 7: 140, 2022.
Article in English | MEDLINE | ID: covidwho-1825669

ABSTRACT

Human infection (or challenge) studies involve the intentional administration of a pathogen (challenge agent) to volunteers. The selection, isolation, development and production of the challenge agent is one of the first steps in developing a challenge study and critical for minimising the risk to volunteers. Regulatory oversight for this production differs globally. Manufacturing agents within a Good Manufacturing Practice (GMP) facility reduces the risk of the manufacturing process by including processes such as confirming the identity of the challenge agent and ascertaining that it's pure and free from impurities. However, in some cases it's not possible or feasible to manufacture to GMP standards, for example where the challenge agent requires an intermediate vector for growth. There is lack of clear guidance on what the minimum requirements for high-quality safe manufacture outside of GMP facilities should be and here we describe the development of a considerations document for the selection and production of challenge agents to meet this need.

2.
Nat Med ; 28(5): 1031-1041, 2022 05.
Article in English | MEDLINE | ID: covidwho-1773989

ABSTRACT

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237 ; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study's primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. All pre-specified primary and secondary objectives were met. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies per milliliter (median, 95% confidence interval (8.41, 9.53)). Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2-4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs present even in asymptomatic infection. All infected individuals developed serum spike-specific IgG and neutralizing antibodies. Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70-80% of viable virus had been generated. Thus, with detailed characterization and safety analysis of this first SARS-CoV-2 human challenge study in young adults, viral kinetics over the course of primary infection with SARS-CoV-2 were established, with implications for public health recommendations and strategies to affect SARS-CoV-2 transmission. Future studies will identify the immune factors associated with protection in those participants who did not develop infection or symptoms and define the effect of prior immunity and viral variation on clinical outcome.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Kinetics , Treatment Outcome , Viral Load , Young Adult
3.
Wellcome Open Res ; 7: 49, 2022.
Article in English | MEDLINE | ID: covidwho-1761258

ABSTRACT

Background: Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2. Given the significant public interest and the complexity of the potential risks and benefits, it is vital that public views are considered in the design and approval of any such study and that investigators and ethics boards remain accountable to the public. Methods: Mixed methods study comprising online surveys conducted with 2,441 UK adults and in-depth virtual focus groups with 57 UK adults during October 2020 to explore the public's attitudes to a human challenge study with SARS-CoV-2 taking place in the UK. Results: There was overall agreement across the surveys and focus groups that a human challenge study with SARS-CoV-2 should take place in the UK. Transparency of information, trust and the necessity to provide clear information on potential risks to study human challenge study participants were important. The perceived risks of taking part included the risk of developing long-term effects from COVID, impact on personal commitments and mental health implications of isolation. There were a number of practical realities to taking part that would influence a volunteer's ability to participate (e.g. Wi-Fi, access to exercise, outside space and work, family and pet commitments). Conclusions: The results identified practical considerations for teams designing human challenge studies. Recommendations were grouped: 1) messaging to potential study participants, 2) review of the protocol and organisation of the study, and 3) more broadly, making the study more inclusive and relevant. This study highlights the value of public consultation in research, particularly in fields attracting public interest and scrutiny .

4.
Teaching Geography ; 47(1):32-35, 2022.
Article in English | ProQuest Central | ID: covidwho-1755958

ABSTRACT

The impact of the most recent A level reforms (Department for Education (DfE), 2014) and changes to assessment arrangements as a consequence of COVID-19 revived the authors' interest in school-university transition. While the curriculum design process successfully built mandatory requirements for the said skills, it did not create any specific principles on how to embed other key competences-such as critical thinking, problem-solving and decision-making - in the geography curriculum. [...]no systematic methodology exists that can help us define how these might differ in a geography curriculum when compared with other science or social science curricula. Whenever the next stage of the curriculum review cycle arrives, there is an opportunity to move towards (i) a more geographically specific mind-set in relation to a broader set of KSA/competences/ learning outcomes, and (ii) a course that is designed in ways that are much more clearly mindful of the majority of the 'who' and 'what' of A level geography's education purpose (Figure 2). Teachers commented that 'students can't get far without these skills', 'these are skills that develop independent thought and learning needed at university', 'they will be needed when studying * Have we become too concerned with 'minding the gap' between school and university subject specialist geography to the detriment of ensuring that broader competency outcomes are optimised for the vast majority of learners who do not progress to HE geography? * Should we be doing more to build a systematic methodology which far more clearly defines our expectations for A02 (assessment objective 2 - analysis and evaluation), along with attitudes, values and other 'soft' competences?

5.
Wellcome open research ; 7, 2022.
Article in English | EuropePMC | ID: covidwho-1755533

ABSTRACT

Background: Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2. Given the significant public interest and the complexity of the potential risks and benefits, it is vital that public views are considered in the design and approval of any such study and that investigators and ethics boards remain accountable to the public. Methods: Mixed methods study comprising online surveys conducted with 2,441 UK adults and in-depth virtual focus groups with 57 UK adults during October 2020 to explore the public’s attitudes to a human challenge study with SARS-CoV-2 taking place in the UK. Results: There was overall agreement across the surveys and focus groups that a human challenge study with SARS-CoV-2 should take place in the UK. Transparency of information, trust and the necessity to provide clear information on potential risks to study human challenge study participants were important. The perceived risks of taking part included the risk of developing long-term effects from COVID, impact on personal commitments and mental health implications of isolation. There were a number of practical realities to taking part that would influence a volunteer’s ability to participate (e.g. Wi-Fi, access to exercise, outside space and work, family and pet commitments). Conclusions: The results identified practical considerations for teams designing human challenge studies. Recommendations were grouped: 1) messaging to potential study participants, 2) review of the protocol and organisation of the study, and 3) more broadly, making the study more inclusive and relevant. This study highlights the value of public consultation in research, particularly in fields attracting public interest and scrutiny .

6.
Intern Med J ; 52(2): 214-222, 2022 02.
Article in English | MEDLINE | ID: covidwho-1700926

ABSTRACT

BACKGROUND: The COVID-19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence-based therapies to combat disease. In particular, the use of off-label therapies outside of a clinical trial setting has been controversial. AIM: To longitudinally study policies and prescribing practices pertaining to therapies for COVID-19 in Australian health services during 2020. METHODS: Prospective data were collected from participating Australian health services who may care for patients with COVID-19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID-19 policy at their service and use of therapies for COVID-19. RESULTS: Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority (34/39; 87%) of respondents located in a major city. Just over half (20/39) of respondents had a written policy for COVID-19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID-19 cases. At study commencement, hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. CONCLUSION: Our results reflect the reactive nature of prescribing of therapies for COVID-19 and highlight the importance of evidence-based guidelines to assist prescribers.


Subject(s)
COVID-19 , Australia/epidemiology , Health Services , Humans , Pandemics , Policy , Prospective Studies , SARS-CoV-2 , Surveys and Questionnaires
7.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328567

ABSTRACT

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID 50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log 10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.

8.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328367

ABSTRACT

Background: Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2. Given the significant public interest and the complexity of the potential risks and benefits, it is vital that public views are considered in the design and approval of any such study and that investigators and ethics boards remain accountable to the public. Methods: : Mixed methods study comprising online surveys conducted with 2,441 UK adults and in-depth virtual focus groups with 57 UK adults during October 2020 to explore the public’s attitudes to a human challenge study with SARS-CoV-2 taking place in the UK. Results: : There was overall agreement across the surveys and focus groups that a human challenge study with SARS-CoV-2 should take place in the UK. Transparency of information, trust and the necessity to provide clear information on potential risks to study human challenge study participants were important. The perceived risks of taking part included the risk of developing long-term effects from COVID, impact on personal commitments and mental health implications of isolation. There were a number of practical realities to taking part that would influence a volunteer’s ability to participate (e.g. Wi-Fi, access to exercise, outside space and work, family and pet commitments). Conclusions: : The results identified practical considerations for teams designing human challenge studies. Recommendations were grouped: 1) messaging to potential study participants, 2) review of the protocol and organisation of the study, and 3) more broadly, making the study more inclusive and relevant. This study highlights the value of public consultation in research, particularly in fields attracting public interest and scrutiny .

9.
BMJ Glob Health ; 7(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1662312

ABSTRACT

INTRODUCTION: To improve access to assistive products (APs) globally, data must be available to inform evidence-based decision-making, policy development and evaluation, and market-shaping interventions. METHODS: This systematic review was undertaken to identify studies presenting population-based estimates of need and coverage for five APs (hearing aids, limb prostheses, wheelchairs, glasses and personal digital assistants) grouped by four functional domains (hearing, mobility, vision and cognition). RESULTS: Data including 656 AP access indicators were extracted from 207 studies, most of which (n=199, 96%) were cross-sectional, either collecting primary (n=167) or using secondary (n=32) data. There was considerable heterogeneity in assessment approaches used and how AP indicators were reported; over half (n=110) used a combination of clinical and self-reported assessment data. Of 35 studies reporting AP use out of all people with functional difficulty in the corresponding functional domains, the proportions ranged from 4.5% to 47.0% for hearing aids, from 0.9% to 17.6% for mobility devices, and from 0.1% to 86.6% for near and distance glasses. Studies reporting AP need indicators demonstrated >60% unmet need for each of the five APs in most settings. CONCLUSION: Variation in definitions of indicators of AP access have likely led to overestimates/underestimates of need and coverage, particularly, where the relationship between functioning difficulty and the need for an AP is complex. This review demonstrates high unmet need for APs globally, due in part to disparate data across this sector, and emphasises the need to standardise AP data collection and reporting strategies to provide a comparable evidence base to improve access to APs.


Subject(s)
Self-Help Devices , Humans
10.
Intern Med J ; 52(2): 214-222, 2022 02.
Article in English | MEDLINE | ID: covidwho-1398467

ABSTRACT

BACKGROUND: The COVID-19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence-based therapies to combat disease. In particular, the use of off-label therapies outside of a clinical trial setting has been controversial. AIM: To longitudinally study policies and prescribing practices pertaining to therapies for COVID-19 in Australian health services during 2020. METHODS: Prospective data were collected from participating Australian health services who may care for patients with COVID-19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID-19 policy at their service and use of therapies for COVID-19. RESULTS: Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority (34/39; 87%) of respondents located in a major city. Just over half (20/39) of respondents had a written policy for COVID-19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID-19 cases. At study commencement, hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. CONCLUSION: Our results reflect the reactive nature of prescribing of therapies for COVID-19 and highlight the importance of evidence-based guidelines to assist prescribers.


Subject(s)
COVID-19 , Australia/epidemiology , Health Services , Humans , Pandemics , Policy , Prospective Studies , SARS-CoV-2 , Surveys and Questionnaires
12.
Mol Psychiatry ; 26(8): 3920-3930, 2021 08.
Article in English | MEDLINE | ID: covidwho-977261

ABSTRACT

There is growing concern that the social and physical distancing measures implemented in response to the Covid-19 pandemic may negatively impact health in other areas, via both decreased physical activity and increased social isolation. Here, we investigated whether increased engagement with digital social tools may help mitigate effects of enforced isolation on physical activity and mood, in a naturalistic study of at-risk individuals. Passively sensed smartphone app use and actigraphy data were collected from a group of psychiatric outpatients before and during imposition of strict Covid-19 lockdown measures. Data were analysed using Gaussian graphical models: a form of network analysis which gives insight into the predictive relationships between measures across timepoints. Within-individuals, we found evidence of a positive predictive path between digital social engagement, general smartphone use, and physical activity-selectively under lockdown conditions (N = 127 individual users, M = 6201 daily observations). Further, we observed a positive relationship between social media use and total daily steps across individuals during (but not prior to) lockdown. Although there are important limitations on the validity of drawing causal conclusions from observational data, a plausible explanation for our findings is that, during lockdown, individuals use their smartphones to access social support, which may help guard against negative effects of in-person social deprivation and other pandemic-related stress. Importantly, passive monitoring of smartphone app usage is low burden and non-intrusive. Given appropriate consent, this could help identify people who are failing to engage in usual patterns of digital social interaction, providing a route to early intervention.


Subject(s)
COVID-19 , Mobile Applications , Social Media , Communicable Disease Control , Exercise , Humans , Outpatients , Pandemics , SARS-CoV-2 , Smartphone
13.
Int J Health Policy Manag ; 2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-931909

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19. Objective: The objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. METHODS: This study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthemes of the qualitative responses were identified using Braun and Clarke's 6-phase analysis. RESULTS: Four primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic. CONCLUSION: COVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations.

15.
Frontline Gastroenterol ; 12(3): 200-206, 2021.
Article in English | MEDLINE | ID: covidwho-828765

ABSTRACT

OBJECTIVE: Health-related concerns brought on by the COVID-19 pandemic and the impact of specific local and national interventions have not been explored in patients with inflammatory bowel disease (IBD) in the UK. We evaluated perspectives of patients with IBD on the pandemic and effectiveness of information dissemination in addressing concerns. METHODS: We prospectively conducted a survey among patients with IBD during the COVID-19 pandemic to assess concerns, information-seeking behaviours, risk perception, compliance and effect of specific interventions. RESULTS: A total of 228 patients were interviewed of whom 89% reported being concerned about the impact of COVID-19 on their health. Access to at least one IBD-specific clinical interaction during the pandemic (COVID-19 information letter from IBD team, interaction with IBD team or general practitioner, Crohn and Colitis UK website visit) was significantly associated with alleviating concerns (OR 2.66; 95% CI 1.35 to 5.24; p=0.005). Seeking health information solely through unofficial channels (search engines or social media) was less likely to ease concerns (OR 0.15; 95% CI 0.03 to 0.61; p=0.008). A quarter of patients disagreed with their assigned risk groups, with majority perceiving higher-risk profiles. This discordance was greatest in patients within the moderate-risk group and constituted immunosuppression use. Nearly 40% of patients had ongoing concerns with regard to their medications of whom a third felt their concerns were not addressed. CONCLUSION: IBD-specific clinical interactions are associated with alleviation of COVID-19 health concerns. These findings have wider implications and emphasise importance of innovative solutions that facilitate effective communication with patients without overburdening current services.

18.
Eur Urol ; 78(1): 21-28, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-125264

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Disease Management , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic , Societies, Medical , Urologic Diseases/therapy , Urology/standards , COVID-19 , Coronavirus Infections/complications , Europe , Humans , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2 , Urologic Diseases/complications , Urologic Diseases/diagnosis
SELECTION OF CITATIONS
SEARCH DETAIL