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1.
Blood ; 139(16): 2471-2482, 2022 04 21.
Article in English | MEDLINE | ID: mdl-35134130

ABSTRACT

The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins of a primary cancer. We used a novel approach to prioritize immunotherapy targets and identified a cell surface protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down by short-hairpin RNA and CRISPR/nuclease-dead Cas9 (dCas9), we show that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody-drug conjugate in vitro and in vivo.


Subject(s)
Multiple Myeloma , Semaphorins , Cell Membrane/metabolism , Humans , Immunologic Factors , Immunotherapy , Membrane Proteins , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Proteomics , Semaphorins/genetics , Semaphorins/metabolism
2.
J Hepatol ; 78(5): 1028-1036, 2023 05.
Article in English | MEDLINE | ID: mdl-36702176

ABSTRACT

BACKGROUND & AIMS: Mouse models of lineage tracing have helped to describe the important subpopulations of hepatocytes responsible for liver regeneration. However, conflicting results have been obtained from different models. Herein, we aimed to reconcile these conflicting reports by repeating a key lineage-tracing study from pericentral hepatocytes and characterising this Axin2CreERT2 model in detail. METHODS: We performed detailed characterisation of the labelled population in the Axin2CreERT2 model. We lineage traced this cell population, quantifying the labelled population over 1 year and performed in-depth phenotypic comparisons, including transcriptomics, metabolomics and analysis of proteins through immunohistochemistry, of Axin2CreERT2 mice to WT counterparts. RESULTS: We found that after careful definition of a baseline population, there are marked differences in labelling between male and female mice. Upon induced lineage tracing there was no expansion of the labelled hepatocyte population in Axin2CreERT2 mice. We found substantial evidence of disrupted homeostasis in Axin2CreERT2 mice. Offspring are born with sub-Mendelian ratios and adult mice have perturbations of hepatic Wnt/ß-catenin signalling and related metabolomic disturbance. CONCLUSIONS: We find no evidence of predominant expansion of the pericentral hepatocyte population during liver homeostatic regeneration. Our data highlight the importance of detailed preclinical model characterisation and the pitfalls which may occur when comparing across sexes and backgrounds of mice and the effects of genetic insertion into native loci. IMPACT AND IMPLICATIONS: Understanding the source of cells which regenerate the liver is crucial to harness their potential to regrow injured livers. Herein, we show that cells which were previously thought to repopulate the liver play only a limited role in physiological regeneration. Our data helps to reconcile differing conclusions drawn from results from a number of prior studies and highlights methodological challenges which are relevant to preclinical models more generally.


Subject(s)
Focal Nodular Hyperplasia , Liver Regeneration , Male , Female , Humans , Liver Regeneration/physiology , Hepatocytes/metabolism , Liver/metabolism , Homeostasis , Cell Proliferation , Axin Protein/genetics
3.
J Med Internet Res ; 25: e38404, 2023 03 29.
Article in English | MEDLINE | ID: mdl-36812390

ABSTRACT

BACKGROUND: COVID-19 vaccines remain central to the UK government's plan for tackling the COVID-19 pandemic. Average uptake of 3 doses in the United Kingdom stood at 66.7% as of March 2022; however, this rate varies across localities. Understanding the views of groups who have low vaccine uptake is crucial to guide efforts to improve vaccine uptake. OBJECTIVE: This study aims to understand the public's attitudes toward COVID-19 vaccines in Nottinghamshire, United Kingdom. METHODS: A qualitative thematic analysis of social media posts from Nottinghamshire-based profiles and data sources was conducted. A manual search strategy was used to search the Nottingham Post website and local Facebook and Twitter accounts from September 2021 to October 2021. Only comments in the public domain and in English were included in the analysis. RESULTS: A total of 3508 comments from 1238 users on COVID-19 vaccine posts by 10 different local organizations were analyzed, and 6 overarching themes were identified: trust in the vaccines, often characterized by a lack of trust in vaccine information, information sources including the media, and the government; beliefs about safety including doubts about the speed of development and approval process, the severity of side effects, and belief that the ingredients are harmful; belief that the vaccines are not effective as people can still become infected and spread the virus and that the vaccines may increase transmission through shedding; belief that the vaccines are not necessary due to low perceived risk of death and severe outcomes and use of other protective measures such as natural immunity, ventilation, testing, face coverings, and self-isolation; individual rights and freedoms to be able to choose to be vaccinated or not without judgement or discrimination; and barriers to physical access. CONCLUSIONS: The findings revealed a wide range of beliefs and attitudes toward COVID-19 vaccination. Implications for the vaccine program in Nottinghamshire include communication strategies delivered by trusted sources to address the gaps in knowledge identified while acknowledging some negatives such as side effects alongside emphasizing the benefits. These strategies should avoid perpetuating myths and avoid using scare tactics when addressing risk perceptions. Accessibility should also be considered with a review of current vaccination site locations, opening hours, and transport links. Additional research may benefit from using qualitative interviews or focus groups to further probe on the themes identified and explore the acceptability of the recommended interventions.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Social Media , Vaccines , Humans , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Pandemics , United Kingdom , Vaccination
4.
J Antimicrob Chemother ; 73(5): 1423-1432, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29514268

ABSTRACT

Objectives: To determine whether local trainer-led TARGET antibiotic interactive workshops improve antibiotic dispensing in general practice. Methods: Using a McNulty-Zelen-design randomized controlled trial within three regions of England, 152 general practices were stratified by clinical commissioning group, antibiotic dispensing rate and practice patient list size, then randomly allocated to intervention (offered TARGET workshop that incorporated a presentation, reflection on antibiotic data, promotion of patient and general practice (GP) staff resources, clinical scenarios and action planning, 73 practices) or control (usual practice, 79 practices). The primary outcome measure was total oral antibiotic items dispensed/1000 patients for the year after the workshop (or pseudo-workshop date for controls), adjusted for the previous year's dispensing. Results: Thirty-six (51%) intervention practices (166 GPs, 51 nurses and 101 other staff) accepted a TARGET workshop invitation. In the ITT analysis total antibiotic dispensing was 2.7% lower in intervention practices (95% CI -5.5% to 1%, P = 0.06) compared with controls. Dispensing in intervention practices was 4.4% lower for amoxicillin/ampicillin (95% CI 0.6%-8%, P = 0.02); 5.6% lower for trimethoprim (95% CI 0.7%-10.2%, P = 0.03); and a non-significant 7.1% higher for nitrofurantoin (95% CI -0.03 to 15%, P = 0.06). The Complier Average Causal Effect (CACE) analysis, which estimates impact in those that comply with assigned intervention, indicated 6.1% (95% CI 0.2%-11.7%, P = 0.04) lower total antibiotic dispensing in intervention practices and 11% (95% CI 1.6%-19.5%, P = 0.02) lower trimethoprim dispensing. Conclusions: This study within usual service provision found that TARGET antibiotic workshops can help improve antibiotic use, and therefore should be considered as part of any national antimicrobial stewardship initiatives. Additional local facilitation will be needed to encourage all general practices to participate.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/methods , Drug Utilization/statistics & numerical data , Education, Medical, Continuing/methods , Education/methods , General Practice/methods , Primary Health Care/methods , England , Female , Humans , Male
6.
Fam Pract ; 35(4): 461-467, 2018 07 23.
Article in English | MEDLINE | ID: mdl-29300965

ABSTRACT

Background: The TARGET (Treat Antibiotics Responsibly; Guidance, Education, Tools) Antibiotics Toolkit aims to improve antimicrobial prescribing in primary care through guidance, interactive workshops with action planning, patient facing educational and audit materials. Objective: To explore GPs', nurses' and other stakeholders' views of TARGET. Design: Mixed methods. Method: In 2014, 40 UK GP staff and 13 stakeholders participated in interviews or focus groups. We analysed data using a thematic framework and normalization process theory (NPT). Results: Two hundred and sixty-nine workshop participants completed evaluation forms, and 40 GP staff, 4 trainers and 9 relevant stakeholders participated in interviews (29) or focus groups (24). GP staffs were aware of the issues around antimicrobial resistance (AMR) and how it related to their prescribing. Most participants stated that TARGET as a whole was useful. Participants suggested the workshop needed less background on AMR, be centred around clinical cases and allow more action planning time. Participants particularly valued comparison of their practice antibiotic prescribing with others and the TARGET Treating Your Infection leaflet. The leaflet needed greater accessibility via GP computer systems. Due to time, cost, accessibility and competing priorities, many GP staff had not fully utilized all resources, especially the audit and educational materials. Conclusions: We found evidence that the workshop is likely to be more acceptable and engaging if based around clinical scenarios, with less on AMR and more time on action planning. Greater promotion of TARGET, through Clinical Commissioning Group's (CCG's) and professional bodies, may improve uptake. Patient facing resources should be made accessible through computer shortcuts built into general practice software.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/methods , Attitude of Health Personnel , Health Personnel/education , Primary Health Care , Focus Groups , Health Promotion , Humans , Interviews as Topic , Practice Patterns, Physicians' , Qualitative Research
7.
J Aging Phys Act ; 24(3): 384-92, 2016 07.
Article in English | MEDLINE | ID: mdl-26583695

ABSTRACT

The purpose of this feasibility study was to evaluate the 3-Step Workout for Life program, a 10-week exercise program that included moderate-intensity muscle strength training followed by task-oriented training. Fourteen participants completed the program (mean age = 73 years; SD = 6.83). The Box and Block test (Z = -2.24, p = .03) and the 30-s chair stand test (Z = -2.21, p = .03) indicate improved physical functioning of the upper and lower extremities. More importantly, results of the function component from the Late-Life Function and Disability Instrument (Z = -2.04, p = .04) and motor skills scale from the Assessment of Motor and Process Skills (Z = -2.97, p = .003) indicate subjective and objective improvements on performing activities of daily living. Supplementing moderate-intensity muscle strength exercise with task-oriented training components is feasible. Preliminary data support the effectiveness of 3-Step Workout for Life in reducing late-life disability.


Subject(s)
Activities of Daily Living , Disabled Persons/rehabilitation , Exercise Therapy/methods , Task Performance and Analysis , Aged , Feasibility Studies , Female , Humans , Male , Motor Skills , Muscle Strength/physiology , Treatment Outcome , Vulnerable Populations
8.
Aust J Gen Pract ; 53(8): 554-557, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39099119

ABSTRACT

BACKGROUND AND OBJECTIVES: Climate change is one of the biggest threats to the healthcare sector. In addition, healthcare contributes significantly to greenhouse gas emissions. Virtual consultations are a growing tool to assess patients. The carbon emissions from virtual consultations have the potential to be much smaller than in-person consultations, predominantly through reduced transportation. This study assesses the carbon footprint of general practitioner referrals for skin lesions evaluated by a store-and-forward teledermatology service compared to an estimated equivalent in-person review. METHOD: The carbon footprint of virtual consultations for skin lesions was compared to estimated equivalent in-person reviews based on the average transportation modalities in New Zealand. RESULTS: Virtual consultations for 484 patients resulted in an average saving of 48 km and 11.17 kg carbon dioxide equivalent per consultation compared to equivalent in-person review. DISCUSSION: This study encourages the use of store-and-forward skin lesion assessment as a way of reducing carbon emissions in the healthcare sector.


Subject(s)
Carbon Footprint , Humans , Carbon Footprint/statistics & numerical data , New Zealand , Male , Female , Skin Diseases/diagnosis , Referral and Consultation/statistics & numerical data , Referral and Consultation/standards , Telemedicine/statistics & numerical data , Middle Aged , Adult , Remote Consultation/statistics & numerical data
9.
Soc Sci Med ; 355: 117112, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39029443

ABSTRACT

Risk communication is a key legal and ethical component of shared decision-making. Decisions about total knee replacement, a common surgery, must contend with the fact that a minority of cases result in unintended outcomes, some of which have devastating effects. To understand how risks are communicated during decision-making, we audio-recorded and analysed 62 consultations between surgeons and patients. Various communication methods were evident, including listing risks without elaboration, discussing them in a conversational manner, abrogating discussion of risk, or using decision-tools. Discussion of risks was often brief in nature, and risk communication was sometimes curtailed or deferred by both patients and surgeons. Risks could also be observed to play a part in reinforcing policy norms of the doctor-patient relationship that highlighted patient responsibility. Nevertheless, patients and surgeons in the observed consultations appeared more interested in developing trusting relationships than in discussing risks. Because patients had sometimes experienced considerable deterioration in their knee function before their consultation, were in pain and struggled with mobility, the realities of clinical practice clashed with the policy norms of choice and patient responsibility. Rather, decisions could appear coerced by the disease process rather than being clear-cut examples of self-determination. While policy norms putatively use risk disclosure to frame communication between patients and clinicians as a transaction between customer and technician, the lack of conformity to these norms in the consultations may indicate resistance to this framing. A greater emphasis on determining positive roles for trust and care would help policy to present a nuanced understanding of decision-making. Risk communication could be seen as a factor in the formation of trusting relationships, improving its role in decision-making processes while recognising its inherent tensions with practice.


Subject(s)
Arthroplasty, Replacement, Knee , Physician-Patient Relations , Trust , Humans , Arthroplasty, Replacement, Knee/psychology , Trust/psychology , Male , Female , Middle Aged , Aged , Decision Making , Communication , Decision Making, Shared , Aged, 80 and over
10.
Hosp Pediatr ; 14(10): e426-e431, 2024 10 01.
Article in English | MEDLINE | ID: mdl-39308304

ABSTRACT

OBJECTIVE: Health literacy is the ability to find, understand, and use information and services to inform health-related decisions and actions. Inadequate health literacy is associated with health disparities, poor health outcomes, and increased emergency department (ED) visits and hospitalizations. Children with medical complexity (CMC) have high rates of acute health care utilization. We examined the association of parental health literacy with acute care utilization and costs in CMC. METHODS: This cross-sectional study included parents of CMC receiving primary care at a free-standing children's hospital. We measured parental health literacy using the Single Item Literacy Screener, which measures the assistance needed to read health care materials. Our main predictor was parental health literacy, categorized as adequate versus inadequate. In a sensitivity analysis, we categorized health literacy as never needing assistance versus needing any assistance. Main outcomes were annual ED visits, hospitalizations, and associated costs. RESULTS: Of the 236 parents of CMC, 5.5% had inadequate health literacy. Health literacy was not associated with acute care utilization or associated costs. In our sensitivity analysis, CMC whose parents need any assistance to read health care materials had 188% higher ED costs (adjusted rate ratio 2.88 [95% confidence interval: 1.63-5.07]) and 126% higher hospitalization costs (adjusted rate ratio 2.26 [95% confidence interval: 1.49-3.44]), compared with CMC whose parents never need assistance. CONCLUSIONS: Inadequate parental health literacy was not associated with acute care utilization. However, CMC of parents needing any assistance to read health materials had higher ED and hospitalization costs. Further multicenter studies are needed.


Subject(s)
Emergency Service, Hospital , Health Literacy , Parents , Humans , Health Literacy/statistics & numerical data , Cross-Sectional Studies , Parents/psychology , Female , Male , Emergency Service, Hospital/statistics & numerical data , Child , Hospitalization/statistics & numerical data , Child, Preschool , Adult , Hospitals, Pediatric , Patient Acceptance of Health Care/statistics & numerical data , Adolescent
11.
Chronic Obstr Pulm Dis ; 11(1): 95-100, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-37676641

ABSTRACT

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment option for patients with severe emphysema and hyperinflation refractory to optimal medical care. This therapy is effective in improving functional status and quality of life, underscoring the importance of identifying potential procedure candidates. To our knowledge, scalable strategies to improve the referral of advanced lung disease patients are lacking. This quality improvement project aimed to increase identification and referral for BLVR in a large Veterans Affairs academic medical center. We show implementing case identification within a pulmonary function testing report, in conjunction with provider education, increased referral rates for BLVR. Because of the ubiquity of lung function testing, other advanced lung disease programs may consider adopting this strategy to improve patients' access to timely clinical evaluation and therapy.

12.
Life Sci Alliance ; 7(11)2024 Nov.
Article in English | MEDLINE | ID: mdl-39209534

ABSTRACT

Mitochondrial gene expression is a compartmentalised process essential for metabolic function. The replication and transcription of mitochondrial DNA (mtDNA) take place at nucleoids, whereas the subsequent processing and maturation of mitochondrial RNA (mtRNA) and mitoribosome assembly are localised to mitochondrial RNA granules. The bidirectional transcription of circular mtDNA can lead to the hybridisation of polycistronic transcripts and the formation of immunogenic mitochondrial double-stranded RNA (mt-dsRNA). However, the mechanisms that regulate mt-dsRNA localisation and homeostasis are largely unknown. With super-resolution microscopy, we show that mt-dsRNA overlaps with the RNA core and associated proteins of mitochondrial RNA granules but not nucleoids. Mt-dsRNA foci accumulate upon the stimulation of cell proliferation and their abundance depends on mitochondrial ribonucleotide supply by the nucleoside diphosphate kinase, NME6. Consequently, mt-dsRNA foci are profuse in cultured cancer cells and malignant cells of human tumour biopsies. Our results establish a new link between cell proliferation and mitochondrial nucleic acid homeostasis.


Subject(s)
Cell Cycle , Cell Proliferation , Homeostasis , Mitochondria , RNA, Double-Stranded , RNA, Mitochondrial , Humans , Homeostasis/genetics , RNA, Mitochondrial/metabolism , RNA, Mitochondrial/genetics , RNA, Double-Stranded/metabolism , RNA, Double-Stranded/genetics , Mitochondria/metabolism , Mitochondria/genetics , Cell Cycle/genetics , Cell Proliferation/genetics , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Cell Line, Tumor , Nucleoside-Diphosphate Kinase/metabolism , Nucleoside-Diphosphate Kinase/genetics , Transcription, Genetic
13.
JMIR Dermatol ; 6: e43395, 2023 May 17.
Article in English | MEDLINE | ID: mdl-37632914

ABSTRACT

BACKGROUND: The role of teledermatology for skin lesion assessment has been a recent development, particularly, since the COVID-19 pandemic has impacted the ability to assess patients in person. The growing number of studies relating to this area reflects the evolving interest. OBJECTIVE: This literature review aims to analyze the available research on store-and-forward teledermatology for skin lesion assessment. METHODS: MEDLINE was searched for papers from January 2010 to November 2021. Papers were searched for assessment of time management, effectiveness, and image quality. RESULTS: The reported effectiveness of store-and-forward teledermatology for skin lesion assessment produces heterogeneous results likely due to significant procedure variations. Most studies show high accuracy and diagnostic concordance of teledermatology compared to in-person dermatologist assessment and histopathology. This is improved through the use of teledermoscopy. Most literature shows that teledermatology reduces time to advice and definitive treatment compared to outpatient clinic assessment. CONCLUSIONS: Overall, teledermatology offers a comparable standard of effectiveness to in-person assessment. It can save significant time in expediting advice and management. Image quality and inclusion of dermoscopy have a considerable bearing on the overall effectiveness.

14.
Implement Res Pract ; 4: 26334895231159428, 2023.
Article in English | MEDLINE | ID: mdl-37091538

ABSTRACT

Background: Tobacco-Free Teachers, Tobacco-Free Society (TFT-TFS) is an evidence-based intervention that promotes tobacco use cessation among teachers and tobacco control policies among schools in India. This study tested an implementation model to build Bihar Department of Education (DOE) capacity to support and deliver TFT-TFS within schools, leveraging DOE training infrastructure. Method: We used a training-of-trainers (TOT) "cascade" implementation strategy to embed the TFT-TFS program into the Bihar DOE infrastructure. We trained 46 Cluster Coordinators to train and support Headmasters to implement TFT-TFS in their schools over one academic year. We selected three school districts, representing approximately 46 clusters and 219 schools. We used the RE-AIM framework to assess program adoption (Headmaster participation in at least one of six TFT-TFS trainings), implementation (of four core program components), and reach (teachers' participation in three or more group discussions). Using a non-inferiority design, we hypothesized that program adoption, implementation, and reach would not be inferior to the high standards demonstrated when TFT-TFS was originally tested in the Bihar School Teachers Study. We used self-reported checklists to measure outcomes and SPSS Version 25 to analyze data. Results: For adoption, 94% of Headmasters attended the first training, although participation declined by the sixth training. Among the 112 schools out of 219 with complete Headmaster checklist data, all met our minimum criteria for implementing TFT-TFS. Over 99% of schools posted a school tobacco control policy and distributed quit booklets. However, only 69% of schools met our criteria for program reach. Conclusions: This study outlines the processes for taking a tobacco control intervention to scale and implementing it through the Bihar DOE infrastructure. These findings provide a foundation for other Indian states and low- and middle-income countries to implement tobacco control and other health programs for schoolteachers. Trial registration: NCT05346991. Plain Language Summary: Each year in India, more than 1.2 million people die from tobacco-related causes, and India has the world's highest oral cancer burden. The world needs more evidence on how to bring cost-effective tobacco control interventions to scale, especially in low- and middle-income countries (LMICs). To address this gap, from 2017 to 2021, we examined the process of scaling up Tobacco-Free Teachers, Tobacco-Free Society (TFT-TFS), an evidence-based intervention promoting tobacco use cessation among teachers and tobacco control policies in schools. Our study tested an implementation model aimed at building the Bihar State Department of Education (DOE) capacity to support and deliver TFT-TFS. We used a training-of-trainers model to embed TFT-TFS into Bihar DOE infrastructure, training 46 Cluster Coordinators to in turn train and support Headmasters to implement TFT-TFS over one academic year. We hypothesized that program adoption, implementation, and reach would not be inferior to the high standards demonstrated when we originally tested TFT-TFS through the Bihar School Teachers Study (2013-2017). For adoption, 94% of Headmasters attended the first training, although participation declined by the sixth training. Of 112 schools (out of 219 with complete Headmaster checklist data), all met our minimum criteria for implementing TFT-TFS. Over 99% of schools posted a school tobacco control policy and distributed quit booklets. However, only 69% of schools met our criteria for program reach. Study findings offer other Indian states and LMICs lessons to implement tobacco control and other health programs for schoolteachers within educational systems.

15.
J Cancer ; 14(10): 1837-1847, 2023.
Article in English | MEDLINE | ID: mdl-37476187

ABSTRACT

PURPOSE: Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Despite a well-established knowledge of tumour development, biomarkers to predict patient outcomes are still required. S100 calcium-binding protein A2 (S100A2) has been purposed as a potential marker in many types of cancer, however, the prognostic value of S100A2 in CRC is rarely reported. MATERIAL AND METHODS: In this study, immunohistochemistry (IHC) was performed to identify the prognostic role of S100A2 protein expression in the tumour core of the tissue microarrays (TMAs) in colorectal cancer patients (n=787). Bulk RNA transcriptomic data was used to identify significant genes compared between low and high cytoplasmic S100A2 groups. Multiplex immunofluorescence (mIF) was performed to further study and confirm the immune infiltration in tumours with low and high cytoplasmic S100A2. RESULTS: Low cytoplasmic protein expression of S100A2 in the tumour core was associated with poor survival (HR 0.539, 95%CI 0.394-0.737, P<0.001) and other adverse tumour phenotypes. RNA transcriptomic analysis showed a gene significantly associated with the low cytoplasmic S100A2 group (AKT3, TAGLN, MYLK, FGD6 and ETFDH), which correlated with tumour development and progression. GSEA analysis identifies the enriched anti-tumour and immune activity group of genes in high cytoplasmic S100A2. Additionally, mIF staining showed that high CD3+FOXP3+ and CD163+ inversely associated with low cytoplasmic S100A2 (P<0.001, P=0.009 respectively). CONCLUSION: Our finding demonstrates a prognostic value of S100A2 together with the correlation with immune infiltration in CRC.

16.
BMJ Open ; 12(5): e055239, 2022 05 02.
Article in English | MEDLINE | ID: mdl-35501075

ABSTRACT

OBJECTIVES: Care homes have experienced a high number of COVID-19 outbreaks, and it is therefore important for care home employees to receive the COVID-19 vaccine. However, there is high vaccine hesitancy among this group. We aimed to understand barriers and facilitators to getting the COVID-19 vaccine, as well as views on potential mandatory vaccination policies. DESIGN: Semi-structured interviews. SETTING: Care home employees in North West England. Interviews conducted in April 2021. PARTICIPANTS: 10 care home employees (aged 25-61 years) in the North West, who had been invited to have, but not received the COVID-19 vaccine. RESULTS: We analysed the interviews using a framework analysis. Our analysis identified eight themes: perceived risk of COVID-19, effectiveness of the vaccine, concerns about the vaccine, mistrust in authorities, facilitators to getting the vaccine, views on mandatory vaccinations, negative experiences of care work during the COVID-19 pandemic, and communication challenges. CONCLUSIONS: Making COVID-19 vaccination a condition of deployment may not result in increased willingness to get the COVID-19 vaccination, with most care home employees in this study favouring leaving their job rather than getting vaccinated. At a time when many care workers already had negative experiences during the pandemic due to perceived negative judgement from others and a perceived lack of support facing care home employees, policies that require vaccination as a condition of deployment were not positively received.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Health Personnel , Humans , Pandemics , Vaccination Hesitancy
17.
Vaccines (Basel) ; 10(3)2022 Mar 03.
Article in English | MEDLINE | ID: mdl-35335020

ABSTRACT

Vaccination is vital to protect the public against COVID-19. The aim of this systematic review is to identify and evaluate the effectiveness of interventions to increase COVID-19 vaccine uptake. We searched a range of databases (Embase, Medline, Psychology & Behavioral Science, PsycInfo, Web of Science and NIH Preprints Portfolio) from March 2020 to July 2021 for studies which reported primary quantitative or qualitative research on interventions to increase COVID-19 vaccine uptake. Outcome measures included vaccination uptake and reported intention to vaccinate. Reviews, position papers, conference abstracts, protocol papers and papers not in English were excluded. The NHLBI quality assessment was used to assess risk of bias. In total, 39 studies across 33 papers met the inclusion criteria. A total of 28 were assessed as good quality. They included interventions relating to communication content, communication delivery, communication presentation, policy or vaccination delivery, with 7 measuring vaccination uptake and 32 measuring vaccination intention. A narrative synthesis was conducted, which highlighted that there is reasonable evidence from studies investigating real behaviour suggesting that personalising communications and sending booking reminders via text message increases vaccine uptake. Findings on vaccination intention are mixed but suggest that communicating uncertainty about the vaccine does not decrease intention, whereas making vaccination mandatory could have a negative impact. Although much of the research used experimental designs, very few measured real behavioural outcomes. Understanding which interventions are most effective amongst vaccine-hesitant populations and in the context of booster vaccinations will be important as vaccine roll outs continue across the world.

18.
Health Psychol ; 41(11): 853-863, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36107667

ABSTRACT

OBJECTIVE: We examined whether varying information about long COVID would affect expectations about the illness. METHOD: In October 2021, we conducted a 2 (Illness Description: long COVID vs. ongoing COVID-19 recovery) × 2 (Symptom Uncertainty: uncertainty emphasized vs. not emphasized) × 2 (Efficacy of Support: enhanced vs. basic support) between-subjects randomized online experimental study. Participants (N = 1,110) were presented with a scenario describing a positive COVID-19 test result, followed by one of eight scenarios describing a long COVID diagnosis and then completed outcome measures of illness expectations including: symptom severity, symptom duration, quality of life, personal control, treatment control, and illness coherence. RESULTS: We ran a series of 2 × 2 × 2 ANOVAs on the outcome variables. We found a main effect of illness description: individuals reported longer symptom duration and less illness coherence when the illness was described as long COVID (compared to ongoing COVID-19 recovery). There was a main effect of symptom uncertainty: when uncertainty was emphasized, participants reported longer expected symptom duration (p < .001), less treatment control (p = .031), and less illness coherence (p < .001) than when uncertainty was not emphasized. There was a main effect of efficacy of support: participants reported higher personal control (p = .004) and higher treatment control (p = .037) when support was enhanced (compared to basic support). CONCLUSIONS: Communications around long COVID should avoid emphasizing symptom uncertainty and aim to provide people with access to additional support and information on how they can facilitate their recovery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
COVID-19 , COVID-19/complications , Humans , Motivation , Quality of Life , Post-Acute COVID-19 Syndrome
19.
BMJ Open ; 12(3): e056533, 2022 03 16.
Article in English | MEDLINE | ID: mdl-35296483

ABSTRACT

OBJECTIVES: Individuals who receive a negative lateral flow coronavirus test result may misunderstand it as meaning 'no risk of infectiousness', giving false reassurance. This experiment tested the impact of adding information to negative test result messages about residual risk and the need to continue protective behaviours. DESIGN: 4 (residual risk) × 2 (post-test result behaviours) between-subjects design. SETTING: Online. PARTICIPANTS: 1200 adults from a representative UK sample recruited via Prolific (12-15 March 2021). INTERVENTIONS: Participants were randomly allocated to one of eight messages. Residual risk messages were: (1) 'Your coronavirus test result is negative' (control); (2) message 1 plus 'It's likely you were not infectious when the test was done' (current NHS Test & Trace (T&T); (3) message 2 plus 'But there is still a chance you may be infectious' (elaborated NHS T&T); and (4) message 3 plus infographic depicting residual risk (elaborated NHS T&T+infographic). Each message contained either no additional information or information about the need to continue following guidelines and protective behaviours. OUTCOME MEASURES: (1) Proportion understanding residual risk of infectiousness and (2) likelihood of engaging in protective behaviours (scales 1-7). RESULTS: The control message decreased understanding relative to the current NHS T&T message: 54% versus 71% (Adjusted Odds Ratio (AOR)=0.56 95% CI 0.34 to 0.95, p=0.030). Understanding increased with the elaborated NHS T&T (89%; AOR=3.25 95% CI 1.64 to 6.42, p=0.001) and elaborated NHS T&T+infographic (91%; AOR=5.16 95% CI 2.47 to 10.82, p<0.001) compared with current NHS T&T message. Likelihood of engaging in protective behaviours was unaffected by information (AOR=1.11 95% CI 0.69 to 1.80, χ2(1)=0.18, p=0.669), being high (M=6.4, SD=0.9) across the sample. CONCLUSIONS: A considerable proportion of participants misunderstood the residual risk following a negative test result. The addition of a single sentence ('But there is still a chance you may be infectious') to current NHS T&T wording increased understanding of residual risk. TRIAL REGISTRATION NUMBER: OSF: https://osf.io/byfz3/.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/diagnosis , Humans , Negative Results
20.
BMJ Open ; 12(8): e061027, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35977758

ABSTRACT

OBJECTIVES: To explore public reactions to the COVID-19 pandemic across diverse ethnic groups. DESIGN: Remote qualitative interviews and focus groups in English or Punjabi. Data were transcribed and analysed through inductive thematic analysis. SETTING: England and Wales, June to October 2020. PARTICIPANTS: 100 participants from 19 diverse 'self-identified' ethnic groups. RESULTS: Dismay, frustration and altruism were reported across all ethnic groups during the first 6-9 months of the COVID-19 pandemic. Dismay was caused by participants' reported individual, family and community risks, and loss of support networks. Frustration was caused by reported lack of recognition of the efforts of ethnic minority groups (EMGs), inaction by government to address COVID-19 and inequalities, rule breaking by government advisors, changing government rules around: border controls, personal protective equipment, social distancing, eating out, and perceived poor communication around COVID-19 and the Public Health England COVID-19 disparities report (leading to reported increased racism and social isolation). Altruism was felt by all, in the resilience of National Health Service (NHS) staff and their communities and families pulling together. Data, participants' suggested actions and the behaviour change wheel informed suggested interventions and policies to help control COVID-19. CONCLUSION: To improve trust and compliance future reports or guidance should clearly explain any stated differences in health outcomes by ethnicity or other risk group, including specific messages for these groups and concrete actions to minimise any risks. Messaging should reflect the uncertainty in data or advice and how guidance may change going forward as new evidence becomes available. A contingency plan is needed to mitigate the impact of COVID-19 across all communities including EMGs, the vulnerable and socially disadvantaged individuals, in preparation for any rise in cases and for future pandemics. Equality across ethnicities for healthcare is essential, and the NHS and local communities will need to be supported to attain this.


Subject(s)
COVID-19 , COVID-19/epidemiology , Ethnicity , Humans , Minority Groups , Pandemics , State Medicine
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