Upskilling haematological services for WGS and germline assessments through a regional skin biopsy training programme

NHS England Genomics introduced whole genome sequencing (WGS) with standard-of- care (SoC) genetic testing for haemato-oncology patients who meet eligibility criteria, including patients with acute leukaemia across all ages, and exhausted SoC testing. Alongside, the role of germline mutations in haematological cancers is becoming increasingly recognised. DNA samples are required from the malignant cells (somatic sample) via a bone marrow aspirate, and from non-malignant cells (germline sample) for comparator analysis. Skin biopsy is considered the gold-standard tissue to provide a source of fibroblast DNA for germline analysis. Performing skin punch biopsies is not within the traditional skillset for haematology teams and upskilling is necessary to deliver WGS/germline testing safely, independently and sustainably. A teaching programme was designed and piloted by the dermatology and haematology teams in Sheffield and delivered throughout the NHS trusts in North East & Yorkshire Genomic Laboratory Hub. The training programme consisted of a 90-min session, slides, video and practical biopsy on pork belly or synthetic skin, designed to teach up to six students at one time. To disseminate best practice, the standard operating procedure and patient information used routinely in Sheffield were shared, to be adapted for local service delivery. From January 2021 to December 2022, 136 haematology staff from 11 hospitals, including 34 consultants, 41 registrars, 34 nurses and 8 physician associates, across the NEY GLH region completed the skin biopsy training programme. Feedback from the course was outstanding, with consistently high scores in all categories. Practical components of the course were especially valued;98.6% (71/72) trainees scored the practical element of the programme a top score of 5 out of 5, highlighting that despite the challenges of delivering face-to- face teaching due to COVID-19, teaching of practical skills was highly valued;training in this way could not have been replicated virtually. Costs of the programme have been approximately 16 000, including consultant input and teaching/educational materials. Recent support has been provided by a separately funded Genomic Nurse Practitioner (GNP), with succession planning for the GNP to take over leadership from the consultant dermatologist. Plans are in place to use the remaining budget to disseminate the programme nationally. Our training programme has shown that skin biopsy can be formally embedded into training for haematology consultants, trainees, nursing team, and physician associates. Delivery of training can be effective and affordable across regional GLHs with appropriate leadership and inter-speciality coordination, and ultimately sustainable with specialist nursing staff, including GNPs.

Isometric thumb extension exercise as part of a multimodal intervention for de Quervain's syndrome: A randomised feasibility trial

Introduction: de Quervain's syndrome is a painful condition commonly presented to hand therapists. Exercise is utilised as an intervention, but isometric exercise has not been investigated. We aimed to assess the feasibility and safety of isometric thumb extension exercise for de Quervain's syndrome and to explore differences between high-load and low-load isometric exercise. Method(s): This parallel-group randomised clinical feasibility trial included individuals with de Quervain's syndrome. All participants underwent a 2 week washout period where they received an orthosis, education, and range of motion exercises. Eligible participants were then randomised to receive high or low-load isometric thumb extension exercises, performed daily for 4 weeks. Feasibility and safety were assessed by recruitment and drop-out rates, adherence, adverse events, and participant feedback via semi-structured interviews. Secondary outcomes included patient-reported outcomes for pain and function, and blinded assessment of range of motion and strength. Result(s): Twenty-eight participants were randomised. There were no drop-outs after randomisation, and no serious adverse events. Adherence to exercise was 86.7%, with 84% of participants stating they would choose to participate again. There were clinically and statistically significant improvements in pain and function over time (p < 0.001) but not in range of motion or strength. There were no statistically significant between-group differences. Conclusion(s): Isometric thumb extension exercise within a multimodal approach appears a safe and feasible intervention for people with de Quervain's syndrome. A large multi-centre trial would be required to compare high- and low-load isometric exercises. Further research investigating exercise and multimodal interventions in this population is warranted.Copyright © The Author(s) 2023.

Stereotactic Radiotherapy for the Treatment of Recurrent Refractory Vt in Chagas Disease Patients

Background: Stereotactic radiotherapy (SBRT) is a new therapeutic option for patients with scar related ventricular tachycardia (VT). Objective(s): To describe our experience with the use of SBRT for the treatment of recurrent VT in patients with Chagas Cardiomyopathy (CCM) in whom catheter ablation is not an option. Method(s): We selected patients with Chagas Disease that underwent SBRT for recurrent VT treatment. The target sites of SBRT were planned based on CMR and CT reconstruction on ADAS software, bipolar voltage maps from previous CA procedures and VT morphology induced on a electrophysiologic study performed SBRT planning. Target sites were decided together by electrophysiology and radiation oncology group. Result(s): We performed SBRT in six CCM patients July 2021 to July 2022. Most patients were male (66.7%), mean age 62.3+/-5.7 years-old and EF 28.5% (Q1: 20 Q3:42.7). One patient (16.7%) had two prior catheter ablation, four (66.7%) had one and one patient had no prior ablation, but had severe pulmonary fibrosis after COVID and was O2 dependent. The mean PTV (planning target volume) was 85+/-14 mL and the ITV (internal target volume) was 29+/-4 ml, with safe constraints regarding the esophagus and stomach. In a mean FU of 244+/-173days, 3 (50%) patients presented VT recurrence after blanking period. Two patients died 86 and 50 days after SBRT. The median number of VT episodes reduced from 13 (6.25;44.75) to 7.5 (3;7.5) (P = 0.093). All alive patients stop presenting VT in a median period of 174 (Q1: 44.75: Q3: 199) days, being at the end of the follow-up in a median of 196 (Q1: 137;Q3: 246) days without new VT episodes. Conclusion(s): SBRT presents a high rate of early recurrence in Chagas disease patients that improves during timeCopyright © 2023

No Longer 'Waiting for the Great Leap Forwards'? Advances in Local State-Voluntary and Community Sector Relationships During Covid-19

Despite the significant influence of localism on policy discourses in the UK in recent decades, there has been limited evidence of any fundamental changes in state-civil society relationships. The outbreak of the Covid-19 pandemic in 2020 created a new context for cross-sectoral collaboration, as the local Voluntary and Community Sector (VCS) and local communities moved to the forefront of the crisis response. This paper draws upon 49 semi-structured interviews with local authorities (LAs) and VCS organisations across England, Scotland and Wales, to explore how the pandemic has reshaped LA-VCS collaboration. Examining the evolution of a range of local collaborative frameworks during the Covid-19 crisis, the article examines what enabled these collaborations to develop, how they operated and what insights can be derived regarding both the conditions for collaboration to flourish and the capacity to sustain this going forward. The findings offer insights into what more progressive forms of collaboration might look like during the transition from crisis and into recovery. It contributes to broader debates about whether the models deployed during Covid-19 represent a pathway to more consensus-based collaboration after a decade of antagonism between civil society and the state.

Telehealth development of virtual environmental home visits to facilitate stroke patients discharges from Hospital

Introduction: The Covid-19 pandemic has progressed the use of digital technology in the NHS to enable remote working and reduce the risk of infection transmission in NHS settings (Hutchings 2020) Telehealth is the use of electronic information and telecommunications technologies to enable and support clinical health care, patient and professionals to provide care virtually (Clipper 2020). A research study published by BJOT (2020) identified that remote home visits were feasible depending on visitor abilities, training and visit standardisation (BJOT 2020). Environmental Home visits (EHV) are fundamental to the discharge process to enable identification of appropriate equipment for the safe and timely discharge of stroke survivors. According to the National Clinical Guidelines for Stroke, stroke survivors should be offered assessment and provision of equipment and adaptations (National Clinical Guidelines for Stroke, 2016). In response to the Covid-19 pandemic to ensure safe discharge and reduced direct face-to-face contact virtual environmental home visits (VEHV) on a stroke ward was developed. Method(s): Microsoft Teams was the technology platform used to facilitate VEHV. Visits were arranged with families and caregivers who had access to the technology and were able to understand the technology. Therapists directed the patient's home environment and asked the individuals completing the VEHV for appropriate dimensions and measurements and an environmental home visit document was completed. Result(s): VEHV were completed by both qualified occupational therapists and therapy assistants were then trained to be able to implement VEHV. The use of Microsoft Teams was found to be a suitable technology platform with families and care givers who were technology competent. However where patients families and care givers did not have access to the appropriate technology or were not sufficiently computer literate VEHV's were not appropriate. Conclusion(s): The VEHV were found to be time efficient, improved patient flow, enabled a number of VEHV to be completed in a day and reduced direct face-to-face contact during Covid-19 while still maintaining communication with patient families and care givers.

Atomic spectrometry update - a review of advances in environmental analysis

In the field of air analysis, highlights within this review period included: a new in situ method for measuring resuspended road dust arising from vehicular movements;new ink-printed filter reference materials for black- and elemental-carbon measurements;coupling of a scanning mobility particle sizer to a single-particle-ICP-MS instrument for improved nanoparticle characterisation;developments in total-reflection XRF spectrometry for trace analysis and evaluation of vibrational spectroscopic techniques for measuring respirable crystalline silica in the workplace. The increasing availability of ICP-MS/MS instruments is revolutionising the analysis of environmental samples such as waters for trace elements. The advent of the mass shift mode makes some elements such as P and S much easier to quantify and allows the REEs and some radioisotopes to be determined at much lower concentrations than previously possible. Advances in vapour generation methods are mostly limited to photochemical and chemical vapour generation as reflected in the new table listing the main advances. Solid or liquid phase extraction prior to analysis remains of great interest, although a notable trend is the synthesis of new materials rather than optimisation of commercially available chelating agents and columns. The analytical effort presented in a paper is sometimes much less than the effort put into the synthesis of the materials so one wonders about the likelihood of methods actually being used and results replicated. Notable in the analysis of soils and plants was the unusually large number of review articles - possibly because practical research was hampered by the Covid-19 epidemic. Areas of continued growth were research on nanoparticles, the application of high-resolution continuum source AAS for multielement analysis, the development of miniaturised AES instruments that may ultimately be field-portable and application of LIBS to the analysis of plant materials. A concerted effort to characterise natural minerals that are sufficiently homogeneous to act as reference materials in the microanalysis of geological materials has resulted in the availability of new materials for isotope ratio determinations. Tied to this has been research into U-Pb dating of zircon and a variety of other accessory minerals by LA-ICP-MS and SIMS. New chemometric models have been developed to handle the complex LIBS data arising from the analysis of geological matrices in the field and during ore processing. Studies on the use of ICP-MS/MS to reduce polyatomic interferences in geological applications were widespread, reflecting the availability of such instruments. In contrast, the potential offered by integrating LIBS data with those from LA-ICP-MS has only just started to be explored but is likely to increase with the development of commercial instruments. © 2022 The Royal Society of Chemistry.

Disorganised patellar tendon structure remains inert despite continued exposure to high loading environments

Introduction: Ultrasound tissue characterisation (UTC) is a unique imaging modality used to investigate structural changes of the patellar tendon. Adolescent athletes who load their knees may be susceptible to patellar tendon abnormality(s) (PTA), characterised by areas of structural disorganisation. Presence of a PTA is a risk factor for the development of pain and dysfunction. This longitudinal study aimed to investigate patellar tendon structural changes in adolescent athletes with PTA. Method(s): Adolescent basketball, volleyball and Australian Rules football athletes aged 11-14 years were recruited between March and November 2017. Data collection occurred biannually over a 2.5-year period or until ceased with the covid-19 pandemic. Bilateral UTC scans of the patellar tendon were collected at each time point. Tendon structure was quantified into four echotypes (echotype I to IV), with echotype I representing the highest structural integrity and echotype IV representing the least amount of structural integrity. The proportion of each echotype was calculated using UTC software for a region of interest (2cm distal from the disappearance of the inferior patella pole). Statistical analysis was conducted for athletes who presented at the initial data collection session with a PTA(s). Maturity status was defined by Mirwald et al. (2002). Generalised additive modelling and generalised additive mixed modelling were used to investigate the relationship between tendon structure and maturity status. Result(s): Of the 173 adolescent athletes recruited for this longitudinal study, nine athletes presented with a PTA at the initial testing session (n=9/173 = 5.2%). When measured against maturity offset (years away from the peak growth spurt of adolescence) echotype 1 (healthy aligned tendon structure) increased in proportions (df=2.25, f=4.43, p=<0.05) while echotype II decreased (df =2.59, f=3.80, p=<0.05). Echotypes III and IV (representing disorganised tendon structure) remained stable in proportions throughout the duration of this longitudinal study (df =1.0, f=0.24 p=0.6 and df=1.0, f =0.27, p=0.6 respectively). Discussion(s): This longitudinal study demonstrates that despite adolescent athletes having the presence of areas of disorganised tendon structure, the proximal patellar tendon structure improves as seen via an increase in echotype I and decrease in echotype II. Areas of disorganised tendon structure (echotypes III and IV) appear inert during the adolescent growth spurt, that is, proportions of echotypes neither increase nor decrease despite continued exposure to high loading environments. Impact and application to the field * Imaging of the patellar tendon for adolescent athletes after the initial identification of tendon abnormality may not be useful given these areas of structural disorganisation appear inert. * Management and intervention strategies for adolescent athletes experiencing tendon problems should focus on clinical outcomes rather than imaging as areas of disorganisation are unlikely to change post development of PTA. * Adolescent athletes may continue to train and compete in high loading environments without further increases to areas of structural disorganisation of the tendon. Conflict of Interest Statement: The authors of this were financially supported with an Australian Government Research Training Program (PhD) scholarship and the General Electric and National Basketball Association Orthopaedics and Sports Medicine Collaboration. The authors certify that they have no affiliations or financial involvement with any entity that has a direct financial interest in the subject matter of this research. Copyright © 2022

Male and female adolescent athletes develop patellar tendon abnormalities at different maturity stages: a longitudinal study of 173 athletes

Introduction: Patellar tendon abnormalities have been reported to occur in adolescent athletes who load the patellar tendon. The adolescent growth spurt has been suggested as a critical time-point for the formation of a healthy patellar tendon. Presence of a patellar tendon abnormality has been identified as a risk factor for the development of pain and dysfunction in later life. This longitudinal study aims to investigate factors associated with the development of patellar tendon abnormality during the critical time period of adolescence. Method(s): 173 athletes were recruited from the specialised sporting programs of basketball, volleyball, and Australian Rules football. Athletes were tested biannually for up to 2.5 years or until data collection ceased due to the covid-19 pandemic. To be eligible for inclusion, athletes had to be active in a selected sporting program and be between the ages of 11-14 at the initial data collection. Bilateral patellar tendon ultrasound tissue characterisation scans were conducted at each data collection point for each athlete to identify patellar tendon abnormality. Descriptive analysis was conducted for any athlete that had or went to develop a patellar tendon abnormality during the longitudinal study period. Maturity status of each athlete was calculated via the maturity offset equations (Mirwald et al (2002). Result(s): Seventeen of the 173 (9.8%) athletes developed a patellar tendon abnormality during this longitudinal study. Nine out of 10 male athletes were post-peak height velocity (PHV) when a patellar tendon abnormality developed. All female athletes (n=7) were peri-PHV (one year either side of the peak growth spurt) when they developed a patellar tendon abnormality. Male athletes who developed abnormality reached PHV at 14.5+/-0.5 vs. normative data of 13.7+/-1.4 years. Female athletes who developed abnormality reached PHV at 15.5+/-0.5 vs. normative data of 12.1+/-1.4 years. Discussion(s): The development of patellar tendon abnormalities appears to differ between male and female athletes with female athletes developing abnormality peri-PHV and male athletes developing abnormalities post-PHV. This raises the important question of sex differences in the development of patellar tendon abnormality during the adolescent growth spurt and suggests that adolescent athletes who develop patellar tendon abnormality achieve their peak growth spurt at a later chronological age as opposed to athletes that do not develop patellar tendon abnormality. Impact and application to the field * This longitudinal study is the first to highlight sex differences in the development of patellar tendon abnormality in adolescent athletes, suggesting that aetiology of this condition may differ by sex. * Adolescent athletes who achieve PHV at a later chronological age may be more susceptible to development of patellar tendon abnormalities and thus risk of future knee pain and dysfunction. * Clinicians should consider and monitor maturity status of adolescent athletes identified as being at risk of developing patellar tendon problems, paying particular attention to athletes who experience a delayed peak growth spurt so that early identification of tendon problems and effective management strategies can be implemented. Conflict of Interest Statement: The authors of this were financially supported with an Australian Government Research Training Program (PhD) scholarship and the General Electric and National Basketball Association Orthopaedics and Sports Medicine Collaboration. The authors certify that they have no affiliations or financial involvement with any entity that has a direct financial interest in the subject matter of this research. Copyright © 2022

Communicating the Science of COVID-19 to Children: Meet the Helpers

This chapter describes and evaluates WUCF’s efforts to adapt their Meet the Helpers program to address the long-standing threat of a global pandemic. It offers a more detailed review of the IDEA (internalization, distribution, explanation, and action) model and introduce the concept of collective efficacy as the ultimate behavioral learning outcome desired in response to COVID’19. The IDEA model has demonstrated its utility as a viable framework for designing and distributing effective instructional messages for mitigating harm and taking protective actions, thereby, providing the theoretical grounding for this analysis. The chapter describes the adaptations made in the Meet the Helpers program to meet the challenge of collective efficacy. Meet the Helpers was distributed through a variety of channels with a consistent message about what the coronavirus is and how to stay safe and healthy. The chapter provides conclusions and recommendations for communicating collective efficacy to children in healthrelated crises such as pandemics. © 2021 John Wiley and Sons Inc.

The impact of COVID-19 lockdown measures on rates of febrile neutropenia in a cohort of Irish patients receiving chemotherapy

Background: Febrile neutropenia in patients receiving chemotherapy is a life-threatening condition requiring prompt attention. This condition may also result in dose reductions, delays, or discontinuations of chemotherapy which compromise patient outcomes. This study seeks to evaluate the impact of COVID19 “lockdown” public health measures in Ireland on the incidence of febrile neutropenia in patients who were receiving cytotoxic chemotherapy regimens. Methods: All patients receiving chemotherapy at the Bon Secours Hospital Cork who were admitted with neutropenia and fever during two separate time periods were included in the study: 1st April 2018 to 31st March 2019 (“pre-pandemic year”) and 1st April 2020 to 31st March 2021 (“pandemic year”). The pandemic year selected equates to a period of heightened infection control measures in Irish society, featuring public health advice re social distancing, routine mask wearing in public and successive lockdown waves. Retrospective chart review was performed on all patients admitted to the oncology inpatient ward who had blood cultures on admission to determine the number of these patients who were neutropenic at the time of blood culture draw. Similarly, pharmacy records were accessed to determine the number of unique chemotherapy items dispensed in each year in order to establish a rate of febrile neutropenia episodes per 100 chemotherapy items dispensed for each period. The incident rate ratio was calculated using the Exact Poisson Test. Results: During the pre-pandemic year there were 57 individual admissions with febrile neutropenia compared with 32 admissions during the pandemic year. There were 4581 chemotherapy units dispensed during the pre-pandemic year compared to 4628 during the pandemic year. The rate of febrile neutropenia episodes per 100 chemotherapy units dispensed was 1.24 (95% CI 0.94, 1.61) in the pre-pandemic year and 0.69 (95% CI 0.47, 0.98) in the pandemic year. The incident rate ratio is 1.80 (95% CI 1.14, 2.87, two-sided P = 0.007). 9 of 57 (16%) admissions in the pre-pandemic year were associated with positive blood cultures compared with 4 of 32 (13%) in the pandemic year (not significant by Fisher's exact test). Conclusions: Increased precautionary infection control measures during the COVID19 pandemic public health restrictions correlated with a significant reduction in the rate of febrile neutropenia amongst patients receiving cytotoxic chemotherapy. This suggests that there may be a role for similar measures for this patient cohort in the post-pandemic period. Options which patients may consider to employ include social distancing, wearing face-coverings and restricting social contacts while at risk of neutropenia from cytotoxic chemotherapy regimens.

Interim Results of a Phase I Study Investigating a Cord Blood-Derived Natural Killer Cell Therapy for Patients Hospitalized with COVID-19

Introduction: In the setting of viral infections, including infection with SARS-CoV-2, lymphocyte exhaustion and lymphopenia are common. Patients with COVID-19 who develop lymphopenia, particularly low numbers of circulating natural killer (NK) cells, are at high risk for disease progression. Thus, strategies that overcome profound lymphopenia and restore innate immune function may reduce the severity of COVID-19. One approach is the direct infusion of an exogenous source of healthy, functional NK cells intended to boost the patient’s immune system during the viral infection, enabling elimination of infected cells. “DVX201” is a cord blood-derived allogeneic NK cell therapy that is cryopreserved and intended for “off-the-shelf use” without HLA-matching. Objective: The primary objective of this study is to investigate the safety and to identify the recommended phase II dose and/or the maximum tolerated dose (MTD) of DVX201 in patients hospitalized with COVID-19. Methods: We are conducting an open-label, nonrandomized phase I safety and dose-finding (modified 3+3) study of DVX201 at three dose levels in patients hospitalized with COVID-19. Adult patients with documented SARS-CoV-2 infection were eligible if they were admitted to the hospital, were receiving ≤6 L supplemental oxygen by low flow delivery, and did not have other evidence of cytokine storm based on levels of serum IL-6, C-reactive protein, and ferritin. Results: To date, 9 patients have been enrolled: 3 subjects at each dose level. All dose levels have been well tolerated, with no dose-limiting toxicities, infusion toxicities, or cytokine release syndrome observed. All patients were discharged from the hospital at an average of 5 days post infusion. Blood samples were drawn for correlative studies including persistence of DVX201, pre- and post-infusion immune system characterization, and cytokine panels. Accrual is continuing at the MTD. Discussion: This trial will serve as the proof of concept for the use of DVX201 as an anti-viral treatment for COVID-19. These results will inform the potential role of DVX201 for treatment of other life-threatening viral infections by harnessing NK cells’ innate function to kill virally infected cells, regardless of the etiology of the infection.

Recovery and resilience: how can innovation policy support the response

The coronavirus pandemic has affected many of the factors shaping the R & D and innovation landscape. Innovative businesses, including early stage companies, face running out of cash due to a lack of availability of external finance or funding, and parts of sectors face being wiped out by economic contraction. R & D projects have hit the buffers due to operational restrictions. At the same time, however, there have been some potential positive effects. Businesses have had to innovate rapidly to adapt to new circumstances, resulting in business model changes and investment in new technologies, especially digital solutions. With digitally-enabled solutions becoming in demand, technology companies have made their products freely available. This chapter reviews these changes and discusses the potential impacts of COVID-19 going forward. In this context, the chapter looks at how policies and programmes could be used to best respond to the crisis in ways that may assist with longer-term competitiveness, and the challenges and opportunities that could shape a recovery that places innovation at its centre. It does this through the lens of priorities related to the 2.4% R & D target, supporting innovative companies, and improving innovation diffusion. © Philip McCann and Tim Vorley 2021.

Spatial and Temporal Monitoring of SARS-CoV-2 in a Sewershed

In response to the global pandemic, Clean Water Services (Washington County, Oregon) monitored 4 wastewater treatment plants (WWTPs) and 16 manholes over a period of 15 months to determine whether spatial and temporal trends in SARS-CoV-2 concentrations corresponded with reported COVID-19 cases. A total of 738 samples were analyzed for SARS-CoV-2 using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). SARS-CoV-2 concentrations at WWTPs appeared to be a leading indicator, with increases in wastewater observed two to three weeks before cases rose. Neighborhoods with high LatinX and high poverty populations also had higher SARS-CoV-2 concentrations. Additionally, outbreaks at local food processing plants corresponded with viral peaks in their associated manhole. Surprisingly, SARS-CoV-2 was rarely detected in hospital effluent despite the presence of known cases, and experiments revealed hospital disinfectants can destroy the RNA signal. Collectively, these findings demonstrate the value of wastewater-based epidemiology for monitoring the local burden of COVID-19. Copyright © 2021 Water Environment Federation

Routinized performances of belonging: Everyday practices and relationships in rural and regional areas during the pandemic

The concentration of COVID-19 cases and restrictions in metropolitan areas in 2020 resulted in a re-emergence of the concept of the 'rural idyll' in Australia, with rural and regional areas coming to be associated with a safe and uninterrupted way of life. Implicit in this notion is the assumption that those living in rural and regional areas found their routines and experiences of belonging uninterrupted. We critique this narrative by drawing on qualitative longitudinal data collected from 2006 to 2020, which allows us to examine our participants' experiences of belonging in rural and regional areas both before and during the pandemic. We find that although our participants' experiences of belonging were largely undisturbed by the pandemic, this was not because their lives were not affected more broadly, but because their sense of belonging was established through everyday routines and practices that were maintained during the pandemic.