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BACKGROUND: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. METHODS: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. RESULTS: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. CONCLUSIONS: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. TRIAL REGISTRATION: National Institute of Health Research (NIHR) [IRAS 275992].
Subject(s)
State Medicine , Tissue and Organ Procurement , Adult , Humans , Decision Making , Tissue Donors , EnglandABSTRACT
Introduction: People with long-term health conditions often attend clinics for kidney function tests. The Self-Testing Own Kidneys (STOK) study assessed feasibility of kidney transplant recipients using hand-held devices to self-test kidney function at home and investigated agreement between home self-test and standard clinic test results. Methods: A prospective, observational, single-center, clinical feasibility study (TRN: ISRCTN68116915), with N = 15 stable kidney transplant recipients, investigated blood potassium and creatinine results agreement between index self-tests at home (patient self-testing of capillary blood, using Abbott i-STAT Alinity analyzers [i-STAT]) and reference tests in clinic (staff sampled venous blood, analyzed with laboratory Siemens Advia Chemistry XPT analyzer) using Bland-Altman and error grid analysis. Results: The mean within-patient difference between index and reference test in creatinine was 2.25 µmol/l (95% confidence interval [CI]: -12.13, 16.81 µmol/l) and in potassium was 0.66 mmol/l (95% CI: -1.47, 2.79 mmol/l). All creatinine pairs and 27 of 40 (67.5%) potassium pairs were judged clinically equivalent. Planned follow-up analysis suggests that biochemical variables associated with potassium measurement in capillary blood were predominant sources of paired test result differences. Paired patient and nurse i-STAT capillary blood test potassium results were not statistically significantly different. Conclusions: This small feasibility study observed that training selected patients to competently use hand-held devices to self-test kidney function at home is possible. Self-test creatinine results showed good analytical and clinical agreement with standard clinic test results. Self-test potassium results showed poorer agreement with standard clinic test results; however, patient self-use of i-STATs at home was not a statistically significant source of difference between paired potassium test results.
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BACKGROUND: In Spring 2020 there was a change in organ donation legislation in England (UK). Much is known about public opinions to organ donation and the change in legislation, however, there is little evidence about the opinions of the NHS workforce. This study set out to understand the levels of awareness, support and action of NHS staff to this change and explore the impact of respondent demographics, place and type of work on awareness, support and action. METHODS: An online survey was offered to all NHS organisations in North Thames and the North East and North Cumbria through the NIHR Clinical Research Network between July and December 2020. Participating organisations were provided with an information package and promoted the survey via email and internal staff communications. Associations were compared univariately using chi-square tests and logistic regression was used for multivariable analysis to compare findings with NHS Blood and Transplant public Kantar survey data. RESULTS: A total of 5789 staff participated in the survey. They were more aware, more supportive, more likely to have discussed their organ donation choices with family and more likely to be on the organ donor register than the public. This increased awareness and support was found across minority ethnic and religious groups. Those working in a transplanting centre were most aware and supportive and those working in the ambulance service were most likely to 'opt-in' following the change in legislation. CONCLUSIONS: NHS staff in England were well informed about the change in organ donation legislation and levels of support were high. NHS staff were six times more likely than the public to have a conversation with their family about their organ donation choices. The size and ethnic diversity of the NHS workforce offers an opportunity to enable and support NHS staff to be advocates for organ donation and raise awareness of the change in legislation amongst their communities.
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BACKGROUND: In early 2020, little was known about treatments for COVID-19. The UK responded by initiating a call for research, leading to the formation of the National Institute for Health Research (NIHR) Urgent Public Health (UPH) group. Fast-track approvals were initiated and support was offered to research sites via the NIHR. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial was designated UPH. High recruitment rates were required for timely results. Recruitment rates were inconsistent across different hospitals and places. PURPOSE: The Factors Affecting Recruitment to the RECOVERY trial study was designed to seek out the facilitators and barriers to recruitment across a population of 3 million served by eight different hospitals and suggest recommendations for recruitment to UPH research during a pandemic situation. METHODS: A qualitative grounded theory study using situational analysis was used. This included a contextualisation of each recruitment site containing prepandemic operational status, prior research activity, COVID-19 admission rates and UPH activity. Additionally, one-to-one interviews using topic guides were completed with NHS staff involved in the RECOVERY trial. Analysis sought out the narratives that shaped recruitment activity. RESULTS: An ideal recruitment situation was identified. The closer sites were able to move towards that ideal situation, the easier they found it to implement the most significant factor on recruitment: embedding research recruitment into standard care. The ability to move to the ideal recruitment situation was mediated by five significant elements: uncertainty, prioritisation, leadership, engagement and communication. CONCLUSION: Embedding recruitment into routine clinical care was the most influential factor on recruitment to the RECOVERY trial. To enable this, sites needed to attain the ideal recruitment situation. Prior research activity, size of site and regulator grading did not correlate with high recruitment rates. Research should be at the forefront of prioritisation during future pandemics.
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COVID-19 , Humans , COVID-19/epidemiology , Pandemics , England/epidemiology , Qualitative Research , Research DesignABSTRACT
OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Azathioprine , Humans , Azathioprine/therapeutic use , Rituximab/therapeutic use , Immunosuppressive Agents/therapeutic use , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Recurrence , Remission Induction , Treatment Outcome , Cyclophosphamide/therapeutic use , Antibodies, Antineutrophil CytoplasmicABSTRACT
Background: There is a known lack of diversity in research participant populations. This impacts on the generalisability of findings and affects clinician prescribing. In the United Kingdom the research community defines those who are underrepresented as under-served. They are commonly those affected by health inequality and disparity. The notion of under-served is complex, with numerous papers identifying multiple factors that contribute to being under-served and in turn suggesting many strategies to improve engagement. Methods: Research professionals in the UK were invited to complete an online survey. The broad aim was to explore their views on under-served groups. The findings were analysed using statistical and qualitative methods to identify enablers and barriers to engaging the under-served. Descriptive statistics were utilised with associations compared univariately by chi-square test and logistic regression for multivariable analysis. Results: A total of 945 completed responses were received. Those identified as under-served in this study reflected the previous body of works with a broader descriptor of ethnic and cultural minorities and the addition of adolescents and young adults. Language and literacy skills had the most impact on being under-served. Only 13% of respondents said they felt equipped to meet the needs of the under-served. The main strategy to increase diversity was community engagement and movement of research delivery into the community. The barriers were funding and time. Training needs identified were linked to community engagement, cultural competence and consent processes. Conclusions: The UK findings from research professionals reflected the previous literature. Adolescents and young people were added to those identified as under-served. Enablers included community outreach and improvement to communication. Barriers were time, funding, organisational processes and lack of focus. Issues were identified with translation and interpretation services. Training requirements focus on methodologies and methods to engage and the consent processes of those from under-served groups.
Research study participants do not reflect the general population. This means that findings from research cannot be reliably transferred to the general population. The people missing are termed under-served or underrepresented. These people come from groups who have unequal access to health care and have poorer health. There are different reasons why people may not take part in research and many ways to support them to take part. This project asked the people who work in research who they thought were missing from research studies. It asked, what would make it easier for people to take part and what got in the way. Those who work in research were invited to write their thoughts in an online survey. Answers were then looked at using tests to find out the number of people who said the same or different things. Other answers were looked at to find out their views and opinions. A total of 945 people filled in the questionnaire. Those who responded thought the biggest group of people who were missing from research populations were from minority social and cultural groups. They also thought teenagers and young adults were missing from research. When asked why people didn't take part the biggest problem was with making research easy to understand. Only 13% of the people who filled in the survey thought they were able to help those who were missing. It was suggested the best way to improve the number of different people taking part in research was to move research from hospitals to the places where the under-served live. The biggest thing that stopped those working in research helping was funding and time. They also wanted to find out how to carry out research in the community, how to help different cultural groups and aid those with certain medical conditions.
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BACKGROUND: Primary care plays an important role in the conception and delivery of transformational research but GP engagement is lacking, prompting calls for the promotion of academic opportunities in primary care. AIM: To identify potential barriers and facilitators among GP trainees and trainers in primary care research to inform support given by Local Clinical Research Networks (LCRNs). DESIGN & SETTING: A cross-sectional online survey was developed and distributed by the CRN to GP trainees and trainers in the North East and North West. METHOD: The survey covered areas including demographics, career intentions, current and potential engagement with research, as well as their general understanding of research in primary care, which included barriers and facilitators to primary care research. RESULTS: Trainees had low intentionality to pursue research and half of trainees did not engage with any research activity. Despite one in five trainees reporting intentions to include research in their career, only 1% would undertake a solely academic career. Medical school region was the only strongly associated factor with academic career intention. Just under 30% of trainers reported engagement in research, but far fewer (8.6%) were interested in contributing to research, and only 10% felt prepared to mentor in research. CONCLUSION: Among trainees, there is limited engagement in and intentionality to pursue research, and this was crucially reflected by responses from trainers. This study identified the need for LCRNs to assist with training in research mentoring and skills, funding opportunities, and to develop resources to promote research in primary care.
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The BNT162b2/Pfizer SARS-CoV-2 vaccine has been widely used in the UK, particularly amongst healthcare workers (HCWs). To establish whether previous COVID-19 influenced vaccine-associated Adverse Events (AEs), we conducted a survey-based study of HCWs in Northeast England. Out of 1238 HCWs, 32% self-reported prior positive PCR and/or antibody test for SARS-CoV-2. Post-dose AEs were worse in those with prior COVID-19 after the first, but not the second dose of vaccine. Second dose AEs were greater in frequency/severity, regardless of COVID-19 history, and they were more systemic in nature. Women and younger HCW were more likely to report AEs after both doses, while dosing interval had no effect on AEs. Ongoing Symptomatic COVID-19 was associated with greater frequency/severity of AEs after dose 2, but not dose one. Overall, AEs were self-limiting and short-lived (i.e.,<48 h) in nature. These findings have implications for vaccine hesitancy and informing guidelines for recommended dosing protocols.
Subject(s)
BNT162 Vaccine , COVID-19 , COVID-19 Vaccines , Female , Humans , SARS-CoV-2 , Vaccination HesitancyABSTRACT
BACKGROUND: A living-donor kidney transplant is the best treatment for most people with kidney failure. Population cohort studies have shown that lifetime living kidney donor risk is modified by sex, age, ethnicity, body mass index (BMI), comorbidity and relationship to the recipient. OBJECTIVES: We investigated whether the UK population of living kidney donors has changed over time, investigating changes in donor demographics. DESIGN: We undertook a cross-sectional analysis of the UK living kidney donor registry between January 2006 to December 2017. Data were available on living donor sex, age, ethnicity, BMI, hypertension and relationship to recipient. SETTING: UK living donor registry. PARTICIPANTS: 11 651 consecutive living kidney donors from January 2006 to December 2017. OUTCOME MEASURES: Living kidney donor demographic characteristics (sex, age, ethnicity, BMI and relationship to the transplant recipient) were compared across years of donation activity. Donor characteristics were also compared across different ethnic groups. RESULTS: Over the study period, the mean age of donors increased (from 45.8 to 48.7 years, p<0.001), but this change appears to have been limited to the White population of donors. Black donors were younger than White donors, and a greater proportion were siblings of their intended recipient and male. The proportion of non-genetically related non-partner donations increased over the 12-year period of analysis (p value for linear trend=0.002). CONCLUSIONS: The increasing age of white living kidney donors in the UK has implications for recipient and donor outcomes. Despite an increase in the number of black, Asian and minority ethnic individuals waitlisted for a kidney transplant, there has been no increase in the ethnic diversity of UK living kidney donors. Black donors in the UK may be at a much greater risk of developing kidney failure due to accumulated risks: whether these risks are being communicated needs to be investigated.
Subject(s)
Kidney Transplantation , Living Donors/statistics & numerical data , Registries , Cross-Sectional Studies , Demography , Ethnicity/statistics & numerical data , Female , Humans , Male , Middle Aged , United KingdomABSTRACT
OBJECTIVES: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. METHODS: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. RESULTS: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19-89), prior disease duration 5.0 years (range 0.4-34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. CONCLUSIONS: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antirheumatic Agents/administration & dosage , Glucocorticoids/administration & dosage , Rituximab/administration & dosage , Adult , Aged , Aged, 80 and over , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Drug Therapy, Combination , Female , Humans , Induction Chemotherapy , Male , Middle Aged , Prospective Studies , Recurrence , Treatment Outcome , Young AdultABSTRACT
Denys-Drash syndrome (DDS) is caused by heterozygous mutations of the Wilms' tumour suppressor gene, WT1, characterised by early-onset diffuse mesangial sclerosis often associated with male pseudohermaphroditism and/or Wilms' tumourigenesis. Previously, we reported that the Wt1tmT396 allele induces DDS kidney disease in mice. In the present study heterozygotes (Wt1tmT396/+) were generated on inbred (129/Ola), crossbred (B6/129) and MF1 second backcross (MF1-N2) backgrounds. Whereas male heterozygotes on each background were fertile, inbred heterozygous females were infertile. Kidney disease (proteinuria and sclerosis) was not congenital and developed significantly earlier in inbred mice, although with variable onset. Disease onset in MF1-N2 stocks occurred later in Wt1tmT396/+ mice than reported previously for Wt1R394W/+ mice, and while no kidney disease has been reported in B6/129 Wt1+/- mice, B6/129 Wt1tmT396/+ mice were affected. Offspring of both male and female B6/129 and MF1-N2 Wt1tmT396/+ mice developed kidney disease, but its incidence was significantly higher in offspring of female heterozygotes. Wt1tmT396/tmT396 embryos exhibited identical developmental abnormalities to those reported for Wt1-/- embryos. The results indicate that the Wt1 (tmT396) allele does not predispose to Wilms' tumourigenesis or male pseudohermaphroditism, its effect on kidney disease and female fertility depends on genetic background, stochastic factors may affect disease onset, and disease transmission is subject to a partial parent-of-origin effect. Since the Wt1tmT396 allele has no detectable intrinsic functional activity in vivo, and kidney disease progression is affected by the type of Wt1 mutation, the data support the view that DDS nephropathy results from a dominant-negative action rather than WT1 haploinsufficiency or gain-of-function.