Patient engagement as a collaborative process in a large Dutch COVID-19 vaccination study (RECOVAC) - insight into the contribution of patient engagement and learnings for the future.

BACKGROUND: The need for patient engagement in health research has been increasingly acknowledged and accepted in recent years. However, implementation is still limited due to lack of evidence on its value and lack of guidance on how to implement patient engagement. This study aims to provide insight into the contribution of patient engagement in the RECOVAC project, which studied COVID-19 vaccination in kidney patients, and formulate concrete practice-based action perspectives for patient engagement. METHODS: We used a qualitative participatory mixed methods approach, based on the Patient Engagement Monitoring and Evaluation (PEME) framework. Patient engagement and data collection were based on the Reflexive Monitoring in Action (RMA) approach. Data collection included participant observations, open ended questionnaires and interactive reflection sessions. Qualitative analysis was done via a thematic approach. RESULTS: We have described the process of patient engagement systematically, provided insight in its value and found that there is a need for clear aims, expectations and preparations from the start of the engagement process. We have shown that reflection throughout the process is of utmost importance and the same applies to clear communication between researchers and patient representatives. By being part of the consortium patient representatives had direct access to information, straight from the source, on for example the vaccination schedule and medication availability and had indirect influence on decisions made by the National Institute for Public Health and the Environment (RIVM) on preventive measures and treatment against COVID-19. Having experienced patient representatives is important, otherwise training needs to be provided. We also found that patient engagement had impact on conduct and outcomes of research activities itself and may have impact on future research and patient engagement activities in general. CONCLUSION: Patient engagement has changed the course of the project. Concrete practice-based action perspectives have been formulated, which are already being implemented by the Dutch Kidney Patients Association (NVN). Studying patient engagement in a high pace project with high public interest has resulted in lessons learned and will help prepare and implement patient involvement in future research projects. CLINICAL TRIAL REGISTRATION: The RECOVAC studies in which the patient engagement took place are registered at clinicialtrial.gov (NCT04741386 registration date 2021-02-04, NCT04841785 registration date 2021-03-22 and NCT05030974 registration date 2021-08-20).

This article is about the extensive engagement of patients in a scientific research project and what that engagement adds to the project. Although researchers acknowledge the importance of engagement of patients in research projects, it is not happening very often, Because there is not enough scientific evidence on the value of patient engagement and not enough guidance for researcher on how to implement it in their research. We used the Patient Engagement Monitoring and Evaluation (PEME) framework and qualitative participatory mixed methods research to provide insight into patient involvement in the RECOVAC project, which studied COVID-19 vaccination in kidney patients. We also formulated practical guidance for researchers who want to engage patients in their research. We describe the process of patient engagement in the RECOVAC project; what went well and what could be improved. We found that it is important to prepare well, keep reflecting on the engagement process throughout the project with all stakeholders of the project, communicate clearly and have experienced patient representatives involved or have training available for them. Patient engagement had impact on the conduct and outcome of the research activities itself and on activities outside of the project (e.g., doctors changing their conversations with their patients). We can conclude that involving patients changed the project and its outcomes to better fit with the needs of patients. A guideline has been made and is already implemented by the Dutch Kidney Patients Association. The lessons learned from this project will help researchers involve patients in their future projects.

Passive accumulation of alkaloids in non-toxic frogs challenges paradigms of the origins of acquired chemical defenses.

Understanding the origins of novel, complex phenotypes is a major goal in evolutionary biology. Poison frogs of the family Dendrobatidae have evolved the novel ability to acquire alkaloids from their diet for chemical defense at least three times. However, taxon sampling for alkaloids has been biased towards colorful species, without similar attention paid to inconspicuous ones that are often assumed to be undefended. As a result, our understanding of how chemical defense evolved in this group is incomplete. Here we provide new data showing that, in contrast to previous studies, species from each undefended poison frog clade have measurable yet low amounts of alkaloids. We confirm that undefended dendrobatids regularly consume mites and ants, which are known sources of alkaloids. Further, we confirm the presence of alkaloids in two putatively non-toxic frogs from other families. Our data suggest the existence of a phenotypic intermediate between toxin consumption and sequestration-passive accumulation-that differs from active sequestration in that it involves no derived forms of transport and storage mechanisms yet results in low levels of toxin accumulation. We discuss the concept of passive accumulation and its potential role in the origin of chemical defenses in poison frogs and other toxin-sequestering organisms.

Tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade.

Tumor-infiltrating lymphocytes (TILs) have been associated with outcomes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and trastuzumab. However, it remains unclear if TILs could be a prognostic and/or predictive biomarker in the context of dual HER2-targeting treatment. In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial. Although no significant association was seen between TILs and pCR, patients with TIL scores ≥60% demonstrated an excellent 3-year IDFS of 100% (95% CI 100-100), regardless of hormone receptor status, nodal stage and attainment of pCR. Additionally, in patients with hormone receptor positive disease, TILs as a continuous variable showed a trend to a positive association with pCR (adjusted Odds Ratio per 10% increase in TILs 1.15, 95% CI 0.99-1.34, p = 0.070) and IDFS (adjusted Hazard Ratio per 10% increase in TILs 0.71, 95% CI 0.50-1.01, p = 0.058). We found no interactions between TILs and anthracycline treatment. Our results suggest that high TIL scores might be able to identify stage II-III HER2-positive breast cancer patients with a favorable prognosis.

UK student midwives' theoretical knowledge, confidence, and experience of intermittent auscultation of the fetal heart rate during labour: An online cross-sectional survey.

AIM: This study aimed to explore student midwives' theoretical knowledge of intrapartum intermittent auscultation, their confidence in, and their experience of this mode of fetal monitoring. DESIGN AND SETTING: An online cross-section survey with closed and open questions. Descriptive statistics were used to analyse participants' intermittent auscultation knowledge, confidence, and experience. Reflexive thematic analysis was used to identify patterns within the free text about participants' experiences. PARTICIPANTS: Undergraduate midwifery students (n = 303) from Nursing and Midwifery Council-approved educational institutions within the United Kingdom. FINDINGS: Most participants demonstrated good theoretical knowledge. They had witnessed the technique being used in clinical practice, and when performed, the practice was reported to be in line with national guidance. In closed questions, participants reported feeling confident in their intermittent auscultation skills; however, these data contrasted with free-text responses. CONCLUSION: This cross-sectional survey found that student midwives possess adequate knowledge of intermittent auscultation. However, reflecting individual clinical experiences, their confidence in their ability to perform intermittent auscultation varied. A lack of opportunity to practice intermittent auscultation, organisational culture, and midwives' preferences have caused student midwives to question their capabilities with this essential clinical skill, leaving some with doubt about their competency close to registration.

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Tumor characteristics of dissociated response to immune checkpoint inhibition in advanced melanoma.

INTRODUCTION: Immune checkpoint inhibition (ICI) has improved patients' outcomes in advanced melanoma, often resulting in durable response. However, not all patients have durable responses and the patients with dissociated response are a valuable subgroup to identify mechanisms of ICI resistance. METHODS: Stage IV melanoma patients treated with ICI and dissociated response were retrospectively screened for available samples containing sufficient tumor at least at two time-points. Included were one patient with metachronous regressive and progressive lesions at the same site, two patients with regressive and novel lesion at different sites, and three patients with regressive and progressive lesions at different sites. In addition, four patients with acquired resistant tumor samples without a matched second sample were included. RESULTS: In the majority of patients, the progressive tumor lesion contained higher CD8+ T cell counts/mm2 and interferon-gamma (IFNγ) signature level, but similar tumor PD-L1 expression. The tumor mutational burden levels were in 2 out 3 lesions higher compared to the corresponding regressive tumors lesion. In the acquired tumor lesions, high CD8+/mm2 and relatively high IFNγ signature levels were observed. In one patient in both the B2M and PTEN gene a stop gaining mutation and in another patient a pathogenic POLE mutation were found. CONCLUSION: Intrapatient comparison of progressive versus regressive lesions indicates no defect in tumor T cell infiltration, and in general no tumor immune exclusion were observed.

Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats.

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.

BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer.

BACKGROUND: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab. METHODS: From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups. RESULTS: BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes. CONCLUSIONS: In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

Incidence and sociodemographic, living environment and maternal health associations with stillbirth in a tertiary healthcare setting in Kano, Northern Nigeria.

BACKGROUND: Almost two million stillbirths occur annually, most occurring in low- and middle-income countries. Nigeria is reported to have one of the highest stillbirth rates on the African continent. The aim was to identify sociodemographic, living environment, and health status factors associated with stillbirth and determine the associations between pregnancy and birth factors and stillbirth in the Murtala Mohammed Specialist Hospital, Kano, Nigeria. METHODS: A three-month single-site prospective observational feasibility study. Demographic and clinical data were collected. We fitted bivariable and multivariable models for stillbirth (yes/no) and three-category livebirth/macerated stillbirth/non-macerated stillbirth outcomes to explore their association with demographic and clinical factors. FINDINGS: 1,998 neonates and 1,926 mothers were enrolled. Higher odds of stillbirth were associated with low-levels of maternal education, a further distance to travel to the hospital, living in a shack, maternal hypertension, previous stillbirth, birthing complications, increased duration of labour, antepartum haemorrhage, prolonged or obstructed labour, vaginal breech delivery, emergency caesarean-section, and signs of trauma to the neonate following birth. INTERPRETATION: This work has obtained data on some factors influencing stillbirth. This in turn will facilitate the development of improved public health interventions to reduce preventable deaths and to progress maternal health within this site.

A Simplified Approach for Classifying Physical Resilience among Community-Dwelling Older Adults: The Health, Aging, and Body Composition Study.

BACKGROUND: Physical resilience is an emerging concept within the context of aging and geriatric medicine, and we previously developed and validated one such indicator based on the mismatch between persons' frailty level and multimorbidity burden. We sought to develop a simplified version for classifying physical resilience. We also examined the agreement between the simplified version and the original approach and evaluated its predictive validity. METHODS: Participants were 2,457 older adults from the Health, Aging, and Body Composition Study. We constructed a simplified version for quantifying physical resilience based on the multimorbidity burden and level of frailty (score: 0-10). Participants were grouped by the number of diseases and classified into three groups-adapters, expected agers, and premature frailers-based on the mean and SD of frailty score (less than, within, or above one standard deviation of the mean). RESULTS: The Cohen's kappa between the novel resilience classification and the original approach was 0.70, and the percentage of absolute agreement was 85.4%. We observed a steep increase in years of healthy and able life from premature frailers to adapters in the simplified resilience classifications. CONCLUSIONS: We developed a simplified version for quantifying physical resilience in a cohort of initially well-functioning older Black and White adults. The agreement between the simplified version and the original approach is high. Adapters had a longer healthy lifespan than expected agers and premature frailers. This user-friendly indicator could help assess patients' physical resilience in clinical settings.

Identification of potential biomarkers and novel therapeutic targets through genomic analysis of small cell bladder carcinoma and associated clinical outcomes.

OBJECTIVES: Small cell bladder carcinoma (SCBC) represents a rare histologic variant with a poor prognosis and for which no routine biomarkers exist. Limited reports of genomic sequencing in SCBC have demonstrated a high prevalence of TP53 and RB1 gene mutations, though the prognostic value of these and other gene variants in SCBC remains undefined. In this study, we performed targeted genomic sequencing on a cohort of SCBC patients and correlated genomic findings with clinical outcomes to identify potential novel biomarkers. MATERIALS AND METHODS: Thirty-one patients with SCBC and available treatment-naïve tumor specimens were identified from an institutional database (23 limited stage [LS], 8 extensive stage [ES]). Small cell carcinoma specimens were microdissected and subjected to tumor next-generation whole-exon sequencing with a 592 gene panel. Kaplan-Meier techniques and Cox proportional hazards models were used to evaluate genomic aberration association with relapse-free survival (RFS) and overall survival (OS) in the limited stage cohort. RESULTS: The most common pathogenic gene variants included ARID1A (48%), TP53 (48%) and RB1 (48%). Mutations in genes with potential therapeutic targets not routinely evaluated in SCBC included BRCA1/2 (16%), POLE (13%), JAK2 (13%), PDGFB (13%) and FGFR3 (3%). Multiple novel biomarker candidates showed trends for improvements in OS in the LS subset including ERCC2 (HR 0.322, P = 0.122) and RB1 (HR 0.481, P = 0.182), while LS patients with TP53 mutations (HR 2.730, P = 0.056), and MCL1 gene amplification (HR 4.183, P = 0.018) suggested inferior OS. Additionally, gene or copy number variants with potential prognostic benefit included UBR5 and DAXX (P = 0.02, [hazard ratios nonestimable due to zero events in biomarker positive groups]). CONCLUSIONS: These results support the role for tumor genomic profiling in SCBC and identify multiple potential novel biomarkers and therapeutic targets in this rare disease. Efforts to validate these findings should lead to improved decision-making and treatment outcomes in SCBC.

Knowing the entire story - a focus group study on patient experiences with chronic Lyme-associated symptoms (chronic Lyme disease).

BACKGROUND: Healthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients' experiences with CLD & CLD-related care, identify themes and repertories in these patients' narrations, and provide potential ways to improve communication with them. METHODS: Informed by the principles of 'clean language', we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes. RESULTS: Participants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as 'invisible' to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal 'you' and other forms of presupposition). CONCLUSION: Central themes found in CLD patients' communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID.

Midwives' experiences of supporting women's mental health: A mixed-method study.

OBJECTIVE: To explore midwives' skills, knowledge and experiences of supporting women's mental health. RESEARCH DESIGN AND SETTING: This paper reports the second phase of a larger project, the 'Mothers' Mood Study', which recruited women and midwives to explore their experiences of perinatal mental health and service provision and focuses on midwives' experiences of supporting women with perinatal mental health problems. This paper reports on midwives' experiences through self-administered questionnaires and focus groups. Descriptive statistics were used to analyse questionnaire data and focus group data were thematically analysed. PARTICIPANTS: All midwives employed at one Health Board in South Wales UK, were eligible to participate. Recruitment took place between February and October 2018. Questionnaires were completed by 145 midwives and 15 attended one of three focus groups. FINDINGS: Questionnaire data showed the majority of midwives had cared for women with mental health problems, most commonly anxiety (95.0%, n = 138) and depression (87.0%, n = 127). Midwives assessed women's mental health informally by observing or asking questions about mood (99.3%, n = 144), anxiety levels (94.5%, n = 137), levels of support (91.0%, n = 132) and mental health history (95.9%, n = 139). The majority of midwives (82.8%, n = 120) indicated they would make some sort of mental health assessment at least 50% of the time. Around a third of midwives 31.7% (n = 46) reported receiving training relating to perinatal mental health in the previous two years, however only 21.4% (n = 31) of these suggested this had helped them in their practice. Three themes were generated from the focus groups, 1) Conversations 2) Support 3) Knowledge and skills. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: A lack of time and continuity at appointments and a focus on physical health of mother and baby reduced the opportunity for conversations around mental health. In addition a lack of experience reduced midwives' confidence resulting in a low threshold for referring women to other services for support. Midwives' main concerns were a need for training on aspects of day-to-day practice and referral options to support women's mental health. A package of training to improved skills and confidence as well as a clear pathway of care will enable midwives to be better placed to support women's mental health.

Women's experience of mild to moderate mental health problems during pregnancy, and barriers to receiving support.

OBJECTIVE: To explore the experiences of women during pregnancy with mild to moderate mental health problems and describe the barriers to receiving support in relation to their mental health. RESEARCH DESIGN AND PARTICIPANTS: This paper reports part of a larger project which recruited women and midwives in one hospital in Wales. Participants completed questionnaires in early pregnancy in an antenatal clinic, and the characteristics of women with and without symptoms of anxiety and depression compared. All women were invited to express interest in a follow up interview in late pregnancy. Women identified to have depression and anxiety in early pregnancy, but not under the care of perinatal mental health services, were eligible for interview. Interviews were conducted with 20 women using a visual timeline to aid discussion and were thematically analysed. FINDINGS: In late pregnancy mental health disorders were reported by nine women, of which five were diagnosed during adulthood. EPDS scores found 15 women had symptoms of mild to moderate depression and GAD-7 scores indicating 15 women with mild to moderate anxiety. Three themes were identified: moods and emotions - past, present and future; expectations and control; knowledge and conversations. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Due to limited access to specialist perinatal mental health services women relied on support networks and self-care to maintain their mental health. More time and better continuity at antenatal appointments along with improved mental health literacy may increase discussions regarding women's mental health during pregnancy. In addition investment is required to develop strategies and improve access to mental health services for women with mild to moderate mental health problems.

Views of the public about Snacktivity™: a small changes approach to promoting physical activity and reducing sedentary behaviour.

BACKGROUND: Many people do not meet the recommended health guidance of participation in a minimum of 150-300 min of moderate intensity physical activity per week, often promoted as at least 30 min of physical activity on 5 days of the week. This is concerning and highlights the importance of finding innovative ways to help people to be physically active each day. Snacktivity™ is a novel approach that aims to encourage people to do small, 2-5 min bouts of physical activity 'snacks' throughout the whole day, such that they achieve at least 150 min of moderate intensity activity per week. However, before it can be recommended, there is a need to explore whether the concept is acceptable to the public. METHODS: A survey to assess the views of the public about Snacktivity™ was distributed to adult patients registered at six general practices in the West Midlands, UK and to health care employees in the same region. RESULTS: A total of 5989 surveys were sent to patients, of which 558 were returned (9.3%). A further 166 surveys were completed by health care employees. A total of 85% of respondents liked the Snacktivity™ concept. The flexibility of the approach was highly rated. A high proportion of participants (61%) reported that the ability to self-monitor their behaviour would help them to do Snacktivity™ throughout their day. Physically inactive participants perceived that Snacktivity™ would help to increase their physical activity, more than those who were physically active (OR = 0.41, 95% CI: 0.25-0.67). Approximately 90% of respondents perceived that Snacktivity™ was easy to do on a non-working day compared to 60% on a working day. Aerobic activity 'snacks' were preferred to those which were strength based. CONCLUSIONS: The Snacktivity™ approach to promoting physical activity was viewed positively by the public and interventions to test the merits of such an approach now need to be developed and tested in a variety of everyday contexts.

Long-term efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease, on dialysis or after kidney transplantation: a national prospective observational cohort study.

BACKGROUND: COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT. METHODS: In this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection. RESULTS: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events. CONCLUSION: This study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT. TRIAL REGISTRATION: The study protocol has been registered in clinicaltrials.gov ( NCT04841785 ). Current knowledge about this subject COVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation. Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups. Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints. Contribution of this study Assessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5. Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group. Monitoring of (serious) adverse events and development of anti-HLA antibodies. Impact on practice or policy Publication of the study design contributes to harmonization of SARS-CoV-2 vaccine study methodology in kidney patients at high-risk for severe COVID-19. Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy.

Fasting before living-kidney donation: effect on donor well-being and postoperative recovery: study protocol of a multicenter randomized controlled trial.

BACKGROUND: One of the main effectors on the quality of life of living-kidney donors is postoperative fatigue. Caloric restriction (CR) and short-term fasting (STF) are associated with improved fitness and increased resistance to acute stress. CR/STF increases the expression of cytoprotective genes, increases immunomodulation via increased anti-inflammatory cytokine production, and decreases the expression of pro-inflammatory markers. As such, nutritional preconditioning by CR or STF represents a non-invasive and cost-effective method that could mitigate the effects of acute surgery-induced stress and postoperative fatigue. To investigate whether preoperative STF contributes to a reduction in fatigue after living-kidney donation, a randomized clinical trial is indicated. METHODS: We aim to determine whether 2.5 days of fasting reduces postoperative fatigue score in subjects undergoing living-kidney donation. In this randomized study, the intervention group will follow a preoperative fasting regime for 2.5 days with a low-dose laxative, while the control group will receive standard care. The main study endpoint is postoperative fatigue, 4 weeks after living-kidney donation. Secondary endpoints include the effect of preoperative fasting on postoperative hospital admission time, the feasibility of STF, and the postoperative recovery of donor and recipient kidney function. This study will provide us with knowledge of the feasibility of STF and confirm its effect on postoperative recovery. DISCUSSION: Our study will provide clinically relevant information on the merits of caloric restriction for living-kidney donors and recipients. We expect to reduce the postoperative fatigue in living-kidney donors and improve the postoperative recovery of living-kidney recipients. It will provide evidence on the clinical merits and potential caveats of preoperative dietary interventions. TRIAL REGISTRATION: Netherlands Trial Register NL9262 . EudraCT 2020-005445-16 . MEC Erasmus MC MEC-2020-0778. CCMO NL74623.078.21.

A novel use for routine CBCT imaging during radiotherapy to detect COVID-19.

INTRODUCTION: Thoracic CT is a useful tool in the early diagnosis of patients with COVID-19. Typical appearances include patchy ground glass shadowing. Thoracic radiotherapy uses daily cone beam CT imaging (CBCT) to check for changes in patient positioning and anatomy prior to treatment through a qualitative assessment of lung appearance by radiographers. Observation of changes related to COVID-19 infection during this process may facilitate earlier testing improving patient management and staff protection. METHODS: A tool was developed to create overview reports for all CBCTs for each patient throughout their treatment. Reports contain coronal maximum intensity projection (MIP's) of all CBCTs and plots of lung density over time. A single therapeutic radiographer undertook a blinded off-line audit that reviewed 150 patient datasets for tool optimisation in which medical notes were compared to image findings. This cohort included 75 patients treated during the pandemic and 75 patients treated between 2014 and 2017. The process was repeated retrospectively on a subset of the 285 thoracic radiotherapy patients treated between January-June 2020 to assess the efficiency of the tool and process. RESULTS: Three patients in the n = 150 optimisation cohort had confirmed COVID-19 infections during their radiotherapy. Two of these were detected by the reported image assessment process. The third case was not detected on CBCT due to minimal density changes in the visible part of the lungs. Within the retrospective cohort four patients had confirmed COVID-19 based on RT-PCR tests, three of which were retrospectively detected by the reported process. CONCLUSION: The preliminary results indicate that the presence of COVID-19 can be detected on CBCT by therapeutic radiographers. IMPLICATIONS FOR PRACTICE: This process has now been extended to clinical service with daily assessments of all thoracic CBCTs. Changes noted are referred for oncologist review.

Should I stay or should I go? An exploration of the decision-making behavior of acute cardiac patients during the COVID-19 pandemic.

BACKGROUND: During the SARS-COV-2 (COVID-19) pandemic efforts to reduce virus transmission resulted in non-emergency patients being deterred from seeking help. The number of patients presenting with acute cardiac conditions reduced, significantly OBJECTIVES: To explore the decision-making process, and influential factors in that process, of patients and their family during an acute cardiac event. METHODS: A qualitative research design was employed using purposive sampling of patients who experienced an acute cardiac event during the social containment mandates. Semi-structured interviews were conducted, with thematic analysis of interview transcripts. RESULTS: Twenty-five participants were recruited from three UK hospitals. Themes identified were reliance on informal support network, lack of awareness of cardiac symptoms leading to delayed help-seeking, and an indirect COVID-19 effect (e.g. avoiding treatment). CONCLUSIONS: These results highlight the need for informed public health messages, targeting patients and their support networks, that allow those in need of treatment to access care.