Understanding general practitioner and pharmacist preferences for pharmacogenetic testing in primary care: a discrete choice experiment.

Pharmacogenetic testing in the United Kingdom's National Health Service (NHS) has historically been reactive in nature, undertaken in the context of single gene-drug relationships in specialist settings. Using a discrete choice experiment we aimed to identify healthcare professional preferences for development of a pharmacogenetic testing service in primary care in the NHS. Respondents, representing two professions groups (general practitioners or pharmacists), completed one of two survey versions, asking them to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or joint pain. Responses from 235 individuals were included. All respondents preferred pharmacogenetic testing over no testing, though preference heterogeneity was identified. Both professional groups, but especially GPs, were highly sensitive to service design, with uptake varying depending on the service offered. This study demonstrates uptake of a pharmacogenetic testing service is impacted by service design and highlights key areas which should be prioritised within future initiatives.

Pharmacogenetics Clinical Decision Support Systems for Primary Care in England: Co-Design Study.

BACKGROUND: Pharmacogenetics can impact patient care and outcomes through personalizing the selection of medicines, resulting in improved efficacy and a reduction in harmful side effects. Despite the existence of compelling clinical evidence and international guidelines highlighting the benefits of pharmacogenetics in clinical practice, implementation within the National Health Service in the United Kingdom is limited. An important barrier to overcome is the development of IT solutions that support the integration of pharmacogenetic data into health care systems. This necessitates a better understanding of the role of electronic health records (EHRs) and the design of clinical decision support systems that are acceptable to clinicians, particularly those in primary care. OBJECTIVE: Explore the needs and requirements of a pharmacogenetic service from the perspective of primary care clinicians with a view to co-design a prototype solution. METHODS: We used ethnographic and think-aloud observations, user research workshops, and prototyping. The participants for this study included general practitioners and pharmacists. In total, we undertook 5 sessions of ethnographic observation to understand current practices and workflows. This was followed by 3 user research workshops, each with its own topic guide starting with personas and early ideation, through to exploring the potential of clinical decision support systems and prototype design. We subsequently analyzed workshop data using affinity diagramming and refined the key requirements for the solution collaboratively as a multidisciplinary project team. RESULTS: User research results identified that pharmacogenetic data must be incorporated within existing EHRs rather than through a stand-alone portal. The information presented through clinical decision support systems must be clear, accessible, and user-friendly as the service will be used by a range of end users. Critically, the information should be displayed within the prescribing workflow, rather than discrete results stored statically in the EHR. Finally, the prescribing recommendations should be authoritative to provide confidence in the validity of the results. Based on these findings we co-designed an interactive prototype, demonstrating pharmacogenetic clinical decision support integrated within the prescribing workflow of an EHR. CONCLUSIONS: This study marks a significant step forward in the design of systems that support pharmacogenetic-guided prescribing in primary care settings. Clinical decision support systems have the potential to enhance the personalization of medicines, provided they are effectively implemented within EHRs and present pharmacogenetic data in a user-friendly, actionable, and standardized format. Achieving this requires the development of a decoupled, standards-based architecture that allows for the separation of data from application, facilitating integration across various EHRs through the use of application programming interfaces (APIs). More globally, this study demonstrates the role of health informatics and user-centered design in realizing the potential of personalized medicine at scale and ensuring that the benefits of genomic innovation reach patients and populations effectively.

Public preferences for pharmacogenetic testing in the NHS: Embedding a discrete choice experiment within service design to better meet user needs.

AIMS: Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines-a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service. METHODS: Members of the UK population were surveyed via an online panel company. Respondents completed 1 of 2 survey versions, asking respondents to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or pain. A conditional logit model was estimated, before the best functional form for the dataset was identified. Preference heterogeneity was identified via latent class analysis. Coefficients from the final selected models were used to estimate uptake in the context of different hypothetical pharmacogenetic services. RESULTS: Responses from 1993 individuals were included in the analysis. There were no differences observed in preference between the 2 clinical scenarios. Conditional logit analysis, using maximum likelihood estimation, indicated that respondents preferred to have noninvasive tests and wanted their data to be shared between different healthcare organizations to guide future prescribing. There was a preference for regional over national data sharing initiatives, and respondents preferred to have access to their data. Predicted uptake varied considerably, ranging from 51% to >99%, depending on design of the service. CONCLUSION: This study identifies public preferences for a pharmacogenetic testing service and demonstrates how predicted uptake can be impacted by relatively minor adaptations. This highlights areas for prioritization during development of future pharmacogenetic services.

The Implementation of Pharmacogenetics in the United Kingdom.

There is considerable inter-individual variability in the effectiveness and safety of pharmaceutical interventions. This phenomenon can be attributed to a multitude of factors; however, it is widely acknowledged that common genetic variation affecting drug absorption or metabolism play a substantial contributory role. This is a concept known as pharmacogenetics. Understanding how common genetic variants influence responses to medications, and using this knowledge to inform prescribing practice, could yield significant advantages for both patients and healthcare systems. Some health services around the world have introduced pharmacogenetics into routine practice, whereas others are less advanced along the implementation pathway. This chapter introduces the field of pharmacogenetics, the existing body of evidence, and discusses barriers to implementation. The chapter will specifically focus on efforts to introduce pharmacogenetics in the NHS, highlighting key challenges related to scale, informatics, and education.

Using Laser Speckle Contrast Imaging to Quantify Perfusion Quality in Kidney and Pancreas Grafts on Vascular Reperfusion: A Proof-of-Principle Study.

The accuracy of intraoperative graft perfusion assessment still remains subjective, with doppler examination being the only objective adjunct. Laser speckle contrast imaging (LSCI) has been used to assess intraoperative blood flow in neurosurgery and in various surgical specialties. Despite its ability to accurately quantify perfusion at the microvascular level, it has not been clinically evaluated in kidney/kidney-pancreas transplantation for perfusion characterization. We aimed to evaluate the utility of LSCI and identify objective parameters that can be quantified at reperfusion. Methods: This study was registered in ClinicalTrials.gov (NCT04202237). The Moor FLPI-2 blood flow imager was used in 4 patients (1 Simultaneous Pancreas and Kidney, 2 deceased, and 1 living donor kidney transplants) during reperfusion to capture reperfusion data. The following parameters were measured: flux (average speed × concentration of moving red blood cells in the sample volume), doppler centroid, total and valid pixels, valid rate, and total and valid area. Flux data were analyzed with Moor FLPI analysis software. Results: The perfusion characteristics and flux images correlated with initial graft function. Conclusions: LSCI is a safe, noncontact imaging modality that provides real-time, accurate, high-resolution, full field blood flow images and a wide range of flux data to objectively quantify organ reperfusion intraoperatively in kidney/kidney-pancreas transplantation. This modality could be used to develop a robust numerical quantification system for the evaluation and reporting of intraoperative organ perfusion, and aid intraoperative decision-making. Perfusion data could be combined with biomarkers and immunological parameters to more accurately predict graft outcomes.

Accuracy of a tool to prioritise patients awaiting elective surgery: an implementation report.

STUDY OBJECTIVE: The objective of this study was to evaluate the accuracy of a new elective surgery clinical decision support system, the 'Patient Tacking List' (PTL) tool (C2-Ai(c)) through receiver operating characteristic (ROC) analysis. METHODS: We constructed ROC curves based on risk predictions produced by the tool and compared these with actual patient outcomes on a retrospective cohort of patients awaiting elective surgery. RESULTS: A total of 11 837 patients were included across three National Health Service (NHS) hospitals in England. ROC analysis revealed an area under the curve of 0.95 (95% CI 0.92 to 0.98) for mortality and 0.8 (95% CI 0.78 to 0.82) for complications. DISCUSSION: The PTL tool was successfully integrated into existing data infrastructures, allowing real-time clinical decision support and a low barrier to implementation. ROC analysis demonstrated a high level of accuracy to predict the risk of mortality and complications after elective surgery. As such, it may be a valuable adjunct in prioritising patients on surgical waiting lists.Health systems, such as the NHS in England, must look at innovative methods to prioritise patients awaiting surgery in order to best use limited resources. Clinical decision support tools, such as the PTL tool, can improve prioritisation and thus positively impact clinical care and patient outcomes. CONCLUSIONS: The high level of accuracy for predicating mortality and complications after elective surgery using the PTL tool indicates the potential for clinical decision support tools to help tackle rising waiting lists and improve surgical planning.

Pathways to interoperable electronic patient records in health and social care, Part 2: introduction for commissioners, chief clinical information officers and senior medical and social care leaders involved in health IT commissioning and strategy.

Since the start of the 2020 Coronavirus 2019 (COVID-19) pandemic, new models of care have rapidly emerged in both health and social care in the UK. The sharing of structured and unstructured data across care organisations has become increasingly important, especially in transfer of care situations and other services, such as hospital at home. At the same time synchronous and asynchronous communication between professionals, patients and their carers, which integrates with patients' records, is optimising care pathways, improving access to care and enhancing self-management of care, particularly for people with long-term conditions. Interoperability and integration of healthcare records is a complex undertaking with various technical, regulatory and organisational challenges. It requires a long-term commitment, collaboration, and investment for all stakeholders to create a comprehensive, interoperable health and social care information ecosystem across the UK. Engaged understanding of these building blocks by clinical and social care leaders will help ensure today's solutions do not become tomorrow's problems.

The altruistic elderly, a valuable but unrecognised kidney donor group. A case report of an 85-year-old unspecified kidney donor.

BACKGROUND: Kidney transplantation is the definitive treatment for end stage renal disease (ESRD), offering improved quality of life and survival benefit over remaining on dialysis. There is, however, a prevailing significant mismatch between patients awaiting transplantation and available donor kidneys. Over time, initial stringent donor criteria have broadened and organs from extended criteria donors (ECDs) and older donors are now being accepted for transplantation. The spectrum of living donors has also undergone a change from close family members to an increasingly non-related, non-directed altruistic donors, newly classified as 'unspecified' donors. Unspecified elderly donors could be a potential untapped resource to expanding the kidney donor pool globally. CASE PRESENTATION: We present a case of an 85 year and 8 months old individual, who donated to an unrelated non-directed matched recipient in the national deceased donor transplant waiting list with excellent donor and recipient outcomes at 7 years. CONCLUSION: To our knowledge she is one of the oldest reported unspecified living kidney donors in the world to date. This case illustrates that elderly donors in good health can come forward to donate, knowing that it is safe and valuable. Once the immediate perioperative challenges after kidney donation are managed, elderly donors rarely encounter long term sequelae. We therefore report this case to increase awareness and refocus attention of transplant teams on elderly donors as a potential untapped group to help address the organ shortage problem in renal transplantation.

Characterizing pharmacogenetic programs using the consolidated framework for implementation research: A structured scoping review.

Several healthcare organizations have developed pre-emptive pharmacogenetic testing programs, where testing is undertaken prior to the prescription of a medicine. This review characterizes the barriers and facilitators which influenced the development of these programs. A bidirectional citation searching strategy identified relevant publications before a standardized data extraction approach was applied. Publications were grouped by program and data synthesis was undertaken using the Consolidated Framework for Implementation Research (CFIR). 104 publications were identified from 40 programs and 4 multi-center initiatives. 26 (66%) of the programs were based in the United States and 95% in high-income countries. The programs were heterogeneous in their design and scale. The Characteristics of the Intervention, Inner Setting, and Process domains were referenced by 92.5, 80, and 77.5% of programs, respectively. A positive institutional culture, leadership engagement, engaging stakeholders, and the use of clinical champions were frequently described as facilitators to implementation. Clinician self-efficacy, lack of stakeholder knowledge, and the cost of the intervention were commonly cited barriers. Despite variation between the programs, there were several similarities in approach which could be categorized via the CFIR. These form a resource for organizations planning the development of pharmacogenetic programs, highlighting key facilitators which can be leveraged to promote successful implementation.

Enhanced recovery after surgery recommendations for renal transplantation: guidelines.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols are now widely practiced in major surgery, improving postsurgical outcomes. Uptake of these programmes have been slow in kidney transplantation due to challenges in evaluating their safety and efficacy in this high-risk cohort. To date, there are no unified guidance and protocols specific to ERAS in kidney transplantation surgery. This paper aims to summarise current evidence in the literature and develop ERAS protocol recommendations for kidney transplantation recipients. METHODS: PubMed, Cochrane, Embase and Medline databases were screened for studies relevant to ERAS protocols in kidney transplantation, up to August 2021. A secondary search was repeated for each ERAS recommendation to explore the specific evidence base available for each section of the protocol. Randomised controlled trials, case-control and cohort studies were included. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used to evaluate the quality of evidence available and recommendations. RESULTS: We identified six eligible studies with a total of 1225 participants. All studies found a reduction in length of hospital stay without affecting readmission rates. The evidence behind specific pre-operative, intra-operative and post-operative interventions included in current ERAS protocols are reviewed and discussed. CONCLUSION: Compared to other surgical specialties, the evidence base for ERAS in kidney transplantation remains lacking, with further room for research and development. However, significant improvements to patient outcomes are already possible with application of the currently available evidence. This has shown that ERAS in kidney transplantation surgery is safe and feasible, with improved postoperative outcomes.

KidneyCloud: A Clinically-Codesigned Solution to Support Kidney Services with Assessing Patients for Transplantation.

There is a need for IT systems that support the complex needs of data management in kidney transplantation. The KidneyCloud project aims to inform a transplant-specific digital solution by exploring patient pathways and data journeys. This paper reports on the early prototyping of the KidneyCloud clinician interface using an iterative codesign methodology. User workshops identified that for making clinical decisions and adding patients to the national waiting list transplant teams relied heavily on manual processes to access data across systems and organisations. Based on the requirements gathered, a prototype interface was designed to provide a unified view on the available patient data, which aligned with clinical workflows. Interactive prototype screens allowed users to gain hands-on experience and provide rich real-time feedback. This informed the necessary functionalities of the interface, but also helped us understand the capabilities required of the back-end solution.

The evaluation of digital transformation in renal transplantation in the United Kingdom: A national interview study.

BACKGROUND: Care pathways in renal transplantation involve multi-speciality coordination and administration of clinical data across organisational boundaries. The potential for information technology (IT) to support the service through data management, communication and national registration has been reported. However, no previous national-level evaluation on the current state of digital transformation has been undertaken. METHODS: We undertook structured phone interviews with transplant coordinators at all 23 transplant centres in the United Kingdom (UK). The interview covered topics including clinical workflows during transplant referral and current data management processes. Based on established frameworks, we elicited IT capabilities, readiness and infrastructure to evaluate the digital maturity at each centre. We analysed interview data thematically and synthesised results across centres to identify common challenges and inform recommendations. RESULTS: Transplant coordinators across centres reported similar care pathways with patients being referred by to transplant centres from regional renal referral centres. Analysis revealed that a key challenge revolved around the inability to access data across organisational boundaries. This resulted in dependence on postal or electronic mail to transfer clinical data, such as blood results or medication lists. Most centres had a hospital-wide electronic medical record, which was unable to meet the specific workflow requirements of transplantation. This was primarily because implemented solutions were unable to provide a single unified view of transplant-related data. As a result, transplant coordinators reported several workarounds to manage clinical data, such as paper folders, Excel© sheets and scanned files on hospital shared drives. CONCLUSIONS: Existing front-line IT solutions and wider infrastructure did not support the requirements of care pathways in renal transplantation. Digital transformation should focus on the need to surface patient data across organisational boundaries and provide specific views of data that complement the clinical workflow. This study highlights how regional interoperability remains a major priority to support multi-centre specialist services.

Modeling Data Journeys to Inform the Digital Transformation of Kidney Transplant Services: Observational Study.

BACKGROUND: Data journey modeling is a methodology used to establish a high-level overview of information technology (IT) infrastructure in health care systems. It allows a better understanding of sociotechnical barriers and thus informs meaningful digital transformation. Kidney transplantation is a complex clinical service involving multiple specialists and providers. The referral pathway for a transplant requires the centralization of patient data across multiple IT solutions and health care organizations. At present, there is a poor understanding of the role of IT in this process, specifically regarding the management of patient data, clinical communication, and workflow support. OBJECTIVE: To apply data journey modeling to better understand interoperability, data access, and workflow requirements of a regional multicenter kidney transplant service. METHODS: An incremental methodology was used to develop the data journey model. This included review of service documents, domain expert interviews, and iterative modeling sessions. Results were analyzed based on the LOAD (landscape, organizations, actors, and data) framework to provide a meaningful assessment of current data management challenges and inform ways for IT to overcome these challenges. RESULTS: Results were presented as a diagram of the organizations (n=4), IT systems (n>9), actors (n>4), and data journeys (n=0) involved in the transplant referral pathway. The diagram revealed that all movement of data was dependent on actor interaction with IT systems and manual transcription of data into Microsoft Word (Microsoft, Inc) documents. Each actor had between 2 and 5 interactions with IT systems to capture all relevant data, a process that was reported to be time consuming and error prone. There was no interoperability within or across organizations, which led to delays as clinical teams manually transferred data, such as medical history and test results, via post or email. CONCLUSIONS: Overall, data journey modeling demonstrated that human actors, rather than IT systems, formed the central focus of data movement. The IT landscape did not complement this workflow and exerted a significant administrative burden on clinical teams. Based on this study, future solutions must consider regional interoperability and specialty-specific views of data to support multi-organizational clinical services such as transplantation.

Robot-assisted kidney transplantation: an update.

Renal transplantation has become the gold-standard treatment for the majority of patients with established renal failure. Recent decades have seen significant progress in immunosuppressive therapies and advances in post-transplant management of recipients, resulting in improved graft and patient outcomes. However, the open technique of allograft implantation has stood the test of time, remaining largely unchanged. In a world where major advances in surgery have been facilitated by innovations in the fields of biotechnology and medical instrumentation, minimally invasive options have been introduced for the recipient undergoing kidney transplantation. In this review we present the evolution of minimally invasive kidney transplantation, with a specific focus on robot-assisted kidney transplant and the benefits it offers to specific patient groups. We also discuss the ethical concerns that must be addressed by transplant teams considering developing or referring to robotic programs.

Laterality in laparoscopic hand assisted donor nephrectomy - Does it matter anymore? Outcomes of a large retrospective series.

This retrospective study was performed to analyse if laterality of the retrieved living donor kidney had any effect on donor and recipient outcomes after hand assisted laparoscopic donor nephrectomy (HALDN). 739 donors who underwent HALDN between January 2006 and January 2018 at a large tertiary transplant centre in the United Kingdom were included. Donor outcomes in individuals undergoing right versus left HALDN were compared with respect to conversion rates, morbidity, warm and cold ischaemia times and recipient failure rates, vascular and ureteric complications. 604 (81.7%) underwent left HALDN and 135 (18.3%) underwent right HALDN, mean age was 47.1 years and 46.8 years respectively with comparable gender distribution. The operative time was shorter for the left side (p = 0.003) and improved during the study for the left but not the right side. In recipients who received left kidneys there were more early technical failures observed (8 versus 1) though not statistically significant. Most centres prefer performing a left nephrectomy and recipient surgeons prefer a left kidney for transplantation primarily because of having a longer vein. This large study provides reassurance that right HALDN nephrectomy is a safe procedure with similar outcomes to left HALDN.

Surgical management of Encapsulating Peritoneal Sclerosis (EPS) in children: international case series and literature review.

BACKGROUND: Encapsulating Peritoneal Sclerosis (EPS) is a rare phenomenon in paediatric patients with kidney failure treated with peritoneal dialysis (PD). This study highlights clinical challenges in the management of EPS, with particular emphasis on peri-operative considerations and surgical technique. METHODS: Retrospective analysis of all paediatric patients with EPS treated at the Manchester Centre for Transplantation. RESULTS: Four patients were included with a median duration of 78 months on PD. All patients had recurrent peritonitis (> 3 episodes), and all had symptoms within three months of a change of dialysis modality from PD to haemodialysis or transplant. In Manchester, care was delivered by a multi-disciplinary team, including surgeons delivering the adult EPS surgical service with a particular focus on nutritional optimisation, sepsis control, and wound management. The surgery involved laparotomy, lavage, and enterolysis of the small bowel + / - stoma formation, depending on intra-abdominal contamination. Two patients had a formal stoma, which were reversed at three and six months, respectively. Two patients underwent primary closure of the abdomen, whereas two patients had re-look procedures at 48 h with secondary closure. One patient had a post-operative wound infection, which was managed medically. One patient's stoma became detached, leading to an intra-abdominal collection requiring re-laparotomy. The median length of stay was 25 days, and patients were discharged once enteral feeding was established. All patients remained free of recurrence with normal gut function and currently two out of four have functioning transplants. CONCLUSIONS: This series demonstrates 100% survival and parenteral feed independence following EPS surgery. Post-operative morbidity was common; however, with individualised experience-based decision-making and relevant additional interventions, patients made full recoveries. Health and development post-surgery continued, allowing the potential for transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Staggered Dual Kidney Transplantation.

We describe a case where a patient received a successful dual kidney transplantation in a staggered fashion. Two kidneys from a deceased donor were accepted for 2 separate primary intended recipients, however, due to unforeseen circumstances, both kidneys were eventually transplanted in a staggered fashion into an alternate single recipient. The intention behind this method was to enhance the patient's renal function and to prevent the wastage of a kidney. Despite the significantly prolonged cold ischemia times, the recipient has excellent dual graft function after 3 years. The positive outcome underpins the effectiveness of donor kidneys even with prolonged cold ischemia times outside established best practice guidelines. It also reinforces the effectiveness of dual kidney transplantation. Transplant professionals encounter complex situations occasionally where an established evidence-base or aids to decision-making are limited. This case reflects challenges in decision-making, patient counselling and consent, especially when the opportunity for the staggered dual kidney transplantation, with potential increased morbidity, came about as another recipient declined a usable kidney. It also highlights the widely differing risk appetites of different patients. Crucially, it optimised the donation process and procurement of 2 kidneys while preventing wastage. To our knowledge, this is the first report of a staggered dual kidney transplantation in a single recipient.

Radiological initial treatment of vascular catastrophes in pancreas transplantation: Review of current literature.

BACKGROUND: Arterio-enteric fistula (AEF) is a rare but potentially devastating complication of solid organ pancreatic transplantation. Traditional management has been to remove the pancreas-duodenum allograft and control the vascular defect. Interventional radiological (IR) techniques present a new method of managing AEF related haemorrhage without re-operation and the potential to preserve graft function. This paper examines the available literature to assess efficacy and safety of this novel approach. METHODS: Aggregate results tables were constructed from 28 cases identified in the English language literature where IR was used in the management of AEF following pancreas transplantation. Outcomes recorded were death, re-bleeding, surgical intervention required and post intervention graft function. These were analysed with respect to technical factors and graft function at time of presentation. RESULTS: 28 cases of AEF managed by IR methods were identified. Mortality was high at 17.9%. 78.6% of all AEFs were present in failed pancreas allografts. Median time from transplant to bleeding event was 29 months. There was a trend of bleeding event occurring within 12 months of allograft failure or rejection. Of the AEFs present in functioning grafts, graft salvage rate was 33% from available data. Coil embolization or use of haemostatic compressed sponge as primary intervention was associated with a higher rate of re-bleeding and death versus arterial stenting. Arterial stenting resulted in a higher rate of distal ischaemia requiring surgical re-vascularisation. All deaths occurred in patients who did not have a transplant pancreatectomy as part of their definitive treatment. CONCLUSION: IR can be an effective way to manage bleeding in the context of AEF associated with pancreas transplantation. If patient condition allows, it should be the first-choice intervention to manage AEF associated bleeding. Use of arterial stenting is more effective in controlling and preventing further bleeding. In a non-functioning graft, transplant pancreatectomy should be strongly considered, possibly in conjunction with or following arterial stenting.