Social scientists have a robust history of contributing to better understandings of and responses to disease outbreaks. The implementation of qualitative research in the context of infectious ...epidemics, however, continues to lag behind in the delivery, credibility, and timeliness of findings when compared with other research designs. The purpose of this article is to reflect on our experience of carrying out three research studies (a rapid appraisal, a qualitative study based on interviews, and a mixed-methods survey) aimed at exploring health care delivery in the context of COVID-19. We highlight the importance of qualitative data to inform evidence-based public health responses and provide a way forward to global research teams who wish to implement similar rapid qualitative studies. We reflect on the challenges of setting up research teams, obtaining ethical approval, collecting and analyzing data in real-time and sharing actionable findings.
ObjectiveThe COVID-19 pandemic has set unprecedented demand on the healthcare workforce around the world. The UK has been one of the most affected countries in Europe. The aim of this study was to ...explore the perceptions and experiences of healthcare workers (HCWs) in relation to COVID-19 and care delivery models implemented to deal with the pandemic in the UK.MethodsThe study was designed as a rapid appraisal combining: (1) a review of UK healthcare policies (n=35 policies), (2) mass media and social media analysis of front-line staff experiences and perceptions (n=101 newspaper articles, n=1 46 000 posts) and (3) in-depth (telephone) interviews with front-line staff (n=30 interviews). The findings from all streams were analysed using framework analysis.ResultsLimited personal protective equipment (PPE) and lack of routine testing created anxiety and distress and had a tangible impact on the workforce. When PPE was available, incorrect size and overheating complicated routine work. Lack of training for redeployed staff and the failure to consider the skills of redeployed staff for new areas were identified as problems. Positive aspects of daily work reported by HCWs included solidarity between colleagues, the establishment of well-being support structures and feeling valued by society.ConclusionOur study highlighted the importance of taking into consideration the experiences and concerns of front-line staff during a pandemic. Staff working in the UK during the COVID-19 pandemic advocated clear and consistent guidelines, streamlined testing of HCWs, administration of PPE and acknowledgement of the effects of PPE on routine practice.
Substantial evidence has highlighted the importance of considering the mental health of healthcare workers during the COVID-19 pandemic, and several organisations have issued guidelines with ...recommendations. However, the definition of well-being and the evidence base behind such guidelines remain unclear.
The aims of the study are to assess the applicability of well-being guidelines in practice, identify unaddressed healthcare workers' needs and provide recommendations for supporting front-line staff during the current and future pandemics.
This paper discusses the findings of a qualitative study based on interviews with front-line healthcare workers in the UK (n = 33), and examines them in relation to a rapid review of well-being guidelines developed in response to the COVID-19 pandemic (n = 14).
The guidelines placed greater emphasis on individual mental health and psychological support, whereas healthcare workers placed greater emphasis on structural conditions at work, responsibilities outside the hospital and the invaluable support of the community. The well-being support interventions proposed in the guidelines did not always respond to the lived experiences of staff, as some reported not being able to participate in these interventions because of understaffing, exhaustion or clashing schedules.
Healthcare workers expressed well-being needs that aligned with socio-ecological conceptualisations of well-being related to quality of life. This approach to well-being has been highlighted in literature on support of healthcare workers in previous health emergencies, but it has not been monitored during this pandemic. Well-being guidelines should explore the needs of healthcare workers, and contextual characteristics affecting the implementation of recommendations.
This paper examines the impact of disruptions to the organisation and delivery of healthcare services and efforts to re‐order care through emotion management during the COVID‐19 pandemic in the UK. ...Framing care as an affective practice, studying healthcare workers' (HCWs) experiences enables better understanding of how interactions between staff, patients and families changed as a result of the pandemic. Using a rapid qualitative research methodology, we conducted interviews with frontline HCWs in two London hospitals during the peak of the first wave of the pandemic and sourced public accounts of HCWs' experiences of the pandemic from social media (YouTube and Twitter). We conducted framework analysis to identify key factors disrupting caring interactions. Fear of infection and the barriers of physical distancing acted to separate staff from patients and families, requiring new affective practices to repair connections. Witnessing suffering was distressing for staff, and providing a ‘good death’ for patients and communicating care to families was harder. In addition to caring for patients and families, HCWs cared for each other. Infection control measures were important for limiting the spread of COVID‐19 but disrupted connections that were integral to care, generating new work to re‐order interactions.
Background
The COVID-19 pandemic has shed light on fractures in health care systems worldwide and continues to have a significant impact, particularly in relation to the health care workforce. ...Frontline staff have been exposed to unprecedented strain, and delivering care during the pandemic has affected their safety, mental health, and well-being.
Objective
This study aimed to explore the experiences of health care workers (HCWs) delivering care in the United Kingdom during the COVID-19 pandemic to understand their well-being needs, experiences, and strategies used to maintain well-being (at individual and organizational levels).
Methods
We analyzed 94 telephone interviews with HCWs and 2000 tweets about HCWs’ mental health during the first year of the COVID-19 pandemic.
Results
The results were grouped under 6 themes: redeployment, clinical work, and sense of duty; well-being support and HCW’s coping strategies; negative mental health effects; organizational support; social network and support; and public and government support.
Conclusions
These findings demonstrate the need for open conversations, where staff’s well-being needs and the strategies they adopted can be shared and encouraged, rather than implementing top-down psychological interventions alone. At the macro level, the findings also highlighted the impact on HCW’s well-being of public and government support as well as the need to ensure protection through personal protective equipment, testing, and vaccines for frontline workers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Autophagy inhibition improves the effectiveness and overcomes RAF pathway inhibition (RAFi) resistance across multiple CNS tumors and molecularly distinct resistance mechanisms. Mechanistic ...links between autophagy and apoptotic cell death may explain this ability to improve RAFi response and reverse resistance. RAFi sensitive (MAF 794, AM38) and resistant (MAF 794R, MAF 905-3, AM38R, B76) BRAFV600E CNS tumor cell lines were analyzed at baseline, following RAFi (vemurafenib), autophagy inhibition (chloroquine or shRNAs), and combination therapy. Growth assays and caspase activation were monitored by Incucyte Zoom. qRT-PCR evaluated key pro-apoptotic BH3-only members of the BCL-2 family. Broad BH-3 profiling was completed using the Letai JC-1 Plate-Based protocol. Western blot analysis assessed protein levels. Combination pharmacologic treatment caused alterations in key pro-apoptotic BH3-only proteins including an increase in BNIP3L and PUMA. Genetically inhibiting autophagy with shRNAs for ATG5 and ATG7 (proteins required for formation of the autophagosome) produced similar results with increases in both protein and mRNA levels of BNIP3L and PUMA following RAFi treatment. This suggested autophagy-mediated regulation of BH3 proteins functions to determine cellular apoptotic threshold. Caspase activation demonstrated increased effectiveness of combined RAFi and autophagy inhibition overcoming the apoptotic threshold compared to single drug treatment. BH3 profiling demonstrated a dependence on BCL-2 to inhibit apoptosis. BH3 mimetics competitively bind to pro-survival BCL-2 family members, blocking their protective effects and pushing tumor cells towards apoptosis. Autophagy inhibition can also improve treatment response by overcoming the apoptotic threshold in RAFi resistant cells and magnifying the apoptotic response in sensitive cells. BH3 profiling reveals CNS BRAFV600E are BCL-2 dependent cells, unprimed for apoptosis, which may be good candidates for additional treatment with BH3 mimetics such as venetoclax. This presents an attractive treatment for MAPK activated CNS tumors by enhancing apoptotic cell death by targeting the MAPK pathway, autophagy and BH3.
Abstract BACKGROUND Autophagy inhibition improves the effectiveness of RAF pathway inhibition (RAFi) and overcomes resistance mechanisms. Mechanistic links between autophagy and apoptotic cell death ...may explain this ability. BH3 mimetics with autophagy and RAFi further improves this response. METHODS RAFi sensitive (MAF 794, AM38) and resistant (MAF 794R, MAF 905-3, AM38R, B76) BRAFV600E tumor cell lines were analyzed at baseline, following RAFi (vemurafenib), autophagy inhibition (chloroquine or shRNAs), BH3 protein inhibition (navitoclax or shRNAs), and combination therapy. Growth assays and caspase activation were monitored by Incucyte Zoom. qRT-PCR evaluated key pro-apoptotic BH3-only members of the BCL-2 family. BH3 profiling was completed using the Letai JC-1 plate-based protocol. Western blot analysis assessed protein levels. Cell Titer Glo determined cell viability. RESULTS Combination therapy increased key pro-apoptotic BH3-only proteins including PUMA. shRNAs targeting ATG5 and ATG7 (proteins required for autophagosome formation) also increased PUMA protein and mRNA levels following RAFi. This suggests autophagy-mediated regulation of BH3 proteins helps determine cellular apoptotic thresholds. Combined autophagy and RAFi increased caspase activation and cell death compared to single drug treatment. BH3 profiling demonstrated BCL-2 dependence to inhibit apoptosis. Inhibition of pro-survival BCL-2 family members BCL-2 and BCL-XL (pharmacologically and genetically) with RAFi, MEKi, and autophagy inhibition further increased caspase activation and reduced cell viability. CONCLUSIONS BH3 mimetics competitively bind pro-survival BCL-2 family members, increasing apoptosis. Autophagy inhibition improves treatment response by overcoming the apoptotic threshold in RAFi resistant cells and magnifying the apoptotic response in sensitive cells. BH3 profiling reveals CNS BRAFV600E are BCL-2 and BCL-XL dependent, making them good candidates for additional treatment with BH3 mimetics. The addition of navitoclax increased caspase activation and reduced cell viability. Autophagy inhibition can magnify this response even more. This presents an attractive treatment for MAPK activated CNS tumors by enhancing apoptotic cell death by targeting the MAPK pathway, autophagy and BH3.
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