Lymphoedema specialists embedded into community nurse and wound services: impacts and outcomes.

BACKGROUND: Lymphoedema is a progressive condition causing significant alterations to life, exerting pressures on unscheduled care from complications including cellulitis and wounds. An on the ground education programme (OGEP) was implemented to raise knowledge, competence and confidence in lymphoedema management in community clinical services. The aim of this study was to explore the impact and outcomes of the OGEP intervention. METHODS: Data were captured before and after OGEP on 561 lymphoedema patients in the community setting. Data recorded included resource use, costs and outcomes (EQ-5D-5L and LYMPROM). RESULTS: Data demonstrated statistically significant reductions in resource allocations including staff visits (P<0.001), cellulitis admissions (P<0.001), compression consumables and wound dressing costs (P<0.001). Overall, the total mean per patient cost decreased from £1457.10 to £964.40 (including intervention) with outcomes significantly improved in EQ-5D-5L/LYMPROM scores. CONCLUSION: The analysis suggests the OGEP intervention may offer reductions in resource costs and improvements in patient outcomes. OGEP may therefore provide an innovative solution in future care delivery.

Single cell transcriptome analysis of the THY-Tau22 mouse model of Alzheimer's disease reveals sex-dependent dysregulations.

Alzheimer's disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex dependency for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-specific and cell type-agnostic AD-related gene activity changes and their sex-dimorphism for individual genes, pathways and cellular sub-networks, we identified both statistically significant alterations and interpreted the upstream mechanisms controlling them. Our results confirm several significant sex-dependent alterations in gene activity in the THY-Tau22 model mice compared to controls, with more pronounced alterations in females. Both changes shared across multiple cell types and cell type-specific changes were observed. The differential genes showed significant over-representation of known AD-relevant processes, such as pathways associated with neuronal differentiation, programmed cell death and inflammatory responses. Regulatory network analysis of these genes revealed upstream regulators that modulate many of the downstream targets with sex-dependent changes. Most key regulators have been previously implicated in AD, such as Egr1, Klf4, Chchd2, complement system genes, and myelin-associated glycoproteins. Comparing with similar data from the Tg2576 AD mouse model and human AD patients, we identified multiple genes with consistent, cell type-specific and sex-dependent alterations across all three datasets. These shared changes were particularly evident in the expression of myelin-associated genes such as Mbp and Plp1 in oligodendrocytes. In summary, we observed significant cell type-specific transcriptomic changes in the THY-Tau22 mouse model, with a strong over-representation of known AD-associated genes and processes. These include both sex-neutral and sex-specific patterns, characterized by consistent shifts in upstream master regulators and downstream target genes. Collectively, these findings provide insights into mechanisms influencing sex-specific susceptibility to AD and reveal key regulatory proteins that could be targeted for developing treatments addressing sex-dependent AD pathology.

Fiber deprivation and microbiome-borne curli shift gut bacterial populations and accelerate disease in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurological disorder characterized by motor dysfunction, dopaminergic neuron loss, and alpha-synuclein (αSyn) inclusions. Many PD risk factors are known, but those affecting disease progression are not. Lifestyle and microbial dysbiosis are candidates in this context. Diet-driven gut dysbiosis and reduced barrier function may increase exposure of enteric neurons to toxins. Here, we study whether fiber deprivation and exposure to bacterial curli, a protein cross-seeding with αSyn, individually or together, exacerbate disease in the enteric and central nervous systems of a transgenic PD mouse model. We analyze the gut microbiome, motor behavior, and gastrointestinal and brain pathologies. We find that diet and bacterial curli alter the microbiome and exacerbate motor performance, as well as intestinal and brain pathologies, but to different extents. Our results shed important insights on how diet and microbiome-borne insults modulate PD progression via the gut-brain axis and have implications for lifestyle management of PD.

Evaluating the cost of managing patients with cellulitis in Wales, UK: A 20-year population-scale study.

This study aimed to estimate costs associated with managing patients with cellulitis from the UK National Health Service (NHS) perspective. The analysis was undertaken through the Secure Anonymised Information Linkage Databank, which brings together population-scale, individual-level anonymised linked data from a wide range of sources, including 80% of primary care general practices within Wales (population coverage ~3.2 million). The data covered a 20-year period from 1999 to 2019. All patients linked to the relevant codes were tracked through primary care settings, recording the number of general practice visits (number of days with an event recorded) and number of in-patient stays. Resources were valued in monetary terms (£ sterling), with costs determined from national published sources of unit costs. These resources were then extrapolated out to reflect UK NHS costs. This is the first attempt to estimate the financial burden of cellulitis using routine data sources on a national scale. The estimated direct annual costs to the Welsh NHS (£28 554 338) are considerable. In-Patient events and length of stay costs are the main cost drivers, with annual Welsh NHS estimates of £19 664 126 with primary care events costing £8 890 212. Initiatives to support patients and healthcare professionals in identifying early signs/risks of cellulitis, improve the accuracy of initial diagnosis, prevent cellulitis recurrence, and improve evidence-based treatment pathways would result in major financial savings, to both the Welsh and UK NHS. In light of these findings, Wales has developed the innovative National Lymphoedema cellulitis Improvement Programme to address these burdens; providing a proactive model of cellulitis care.

A spotlight on lymphoedema Did Not Attends: Demographics and workforce costs.

This unique evaluation aimed to estimate, the financial impact of non-attendance on a nation-wide hospital lymphoedema service. Along with gaining some understanding of patient characteristics of those who Did Not Attend (DNA) and were subsequently discharged. The evaluation design interrogated existing performance data from 2012 to 2022. This information was used to estimate the costs incurred based on national published sources and pay scales. Staffing costs of over £1.1 m in one decade related to the financial impact of over 23 000 unattended lymphoedema appointments. The characteristics of 870 patients from 2019/2020 were also evaluated suggesting that those with a wound alongside complex lymphoedema were less likely to DNA appointments. Two-thirds of patients were managing two or more comorbidities-obesity, cardiac conditions and diabetes being the most common. It seems likely that some DNAs are avoidable by adapting appointment administrative processes and greater understanding of patients' perception of value. However, the reasons for DNA are likely to be varied and nuanced so potentially a small proportion are unavoidable. Modernising appointment processes and identifying patient value may help minimise DNA costs in the future.

Facilitating Integrated Perinatal Care for Families Affected by Substance Use.

Families of newborns are frequently referred to child protection systems because of parental substance use, yet many families face barriers to accessing prenatal care and substance use treatment services. Although federal legislation requires states to develop Plans of Safe Care to address families' health and substance use treatment needs, few have developed comprehensive and systematic approaches to provide perinatal support to parents and infants. In this commentary, we describe the development and initial testing of a Plan of Safe Care that engages patients and their providers in perinatal care coordination. Developed out of an in-depth analysis of current care workflows at an urban safety net health system, the Plan of Safe Care facilitates conversations with clients around delivery planning and aligns resources to support families with substance use disorders.

Sleeping prone with a left ventricular assist device: Dream or reality?

BACKGROUND: Among many other factors, restrictions on sleeping positions decrease quality of life after durable left ventricular assist device implantation. Specifically, device manufacturers and clinicians typically advise against sleeping in the prone position owing to concerns for driveline disruption, exit site infection, and hemodynamic compromise. Yet, no data exist to inform these recommendations and to the best of our knowledge no studies have examined sleep position in people with left ventricular assist devices. We report the first case of a person with a left ventricular assist device who slept prone, every night, for over one year. CASE: This is a 38-year-old man with a HeartWare™ left ventricular assist device who had previously not disclosed that he was sleeping in the prone position for the 16 months following device implantation. The patient did not suffer any episodes of device-related malfunction, infection, neurologic insult, or hemodynamic compromise. We performed a non-invasive assessment in both supine and prone positions to better understand the hemodynamic effects of the prone position. CONCLUSION: In select recipients of left ventricular assist devices, sleeping in the prone position may be safely tolerated.

Children and young people with lymphoedema: a project to assess the education needs of healthcare professionals.

Healthcare professionals need adequate preparatory education to treat children and young people with lymphoedema confidently and competently. This collaborative international project, based on existing literature and expert focus groups, seeks to identify the nature of that education need and in what format it could be addressed.

Living with lymphoedema: children's and young people's perspectives.

BACKGROUND: Lymphoedema is a chronic condition that requires lifelong, time-consuming and laborious management. It can have significant effects on physical, psychological and social well-being. Children and young people with lymphoedema require access to expert services to aid early diagnosis and referral for assessment and treatment. AIM: To explore the perspectives of children and young people living with lymphoedema and those of their families, as well as their experiences of the national paediatric lymphoedema service in Wales. METHOD: A qualitative approach was adopted using semi-structured interviews with participants who had been referred to the national paediatric lymphoedema service in Wales. FINDINGS: A total of 15 families were interviewed. Five themes were identified: lack of professional awareness of paediatric lymphoedema; a journey to diagnosis as lost in the system; 'being me' - what it feels like to have lymphoedema; managing lymphoedema and feeling supported; and the benefits of a national paediatric lymphoedema service. Two sub-themes were identified within the 'being me' theme - body image and self-esteem, and loss of control. CONCLUSION: Lymphoedema has a profound effect on daily life, body image and self-esteem. Participants tended to be resilient and determined to continue with their lives. Importantly, they valued being under the care of a service that understood their condition.

Single-nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell-type-specific gene regulatory variation.

BACKGROUND: Cell types in ventral midbrain are involved in diseases with variable genetic susceptibility, such as Parkinson's disease and schizophrenia. Many genetic variants affect regulatory regions and alter gene expression in a cell-type-specific manner depending on the chromatin structure and accessibility. RESULTS: We report 20,658 single-nuclei chromatin accessibility profiles of ventral midbrain from two genetically and phenotypically distinct mouse strains. We distinguish ten cell types based on chromatin profiles and analysis of accessible regions controlling cell identity genes highlights cell-type-specific key transcription factors. Regulatory variation segregating the mouse strains manifests more on transcriptome than chromatin level. However, cell-type-level data reveals changes not captured at tissue level. To discover the scope and cell-type specificity of cis-acting variation in midbrain gene expression, we identify putative regulatory variants and show them to be enriched at differentially expressed loci. Finally, we find TCF7L2 to mediate trans-acting variation selectively in midbrain neurons. CONCLUSIONS: Our data set provides an extensive resource to study gene regulation in mesencephalon and provides insights into control of cell identity in the midbrain and identifies cell-type-specific regulatory variation possibly underlying phenotypic and behavioural differences between mouse strains.

Introducing the new Chronic Oedema Wet Leg Pathway.

Reticence to apply compression therapy has been widely observed in clinical practice, compounded by an absence of evidenced-based pathways for application of prompt compression prior to measuring ankle brachial pressure index (ABPI). Importantly, delaying compression therapy for patients with chronic oedema and lymphorrhoea causes many avoidable complications. In 2017, Lymphoedema Network Wales (LNW) developed an evidenced-based pathway to improve the management of chronic oedema and wet legs (lymphorrhoea) for community nurses. During the past 4 years, the Chronic Oedema Wet Leg Pathway has been presented, published and used internationally, as well as being translated into different languages. It is commonly used in community nursing Teams as an evidenced-based document. However, like all documents and guidelines, when more evidence becomes available, the pathway needs updating. Therefore, this clinical focus article will present the new and enhanced Chronic Oedema Wet Leg Pathway, introducing a new level four compression section, which increases the layers of compression bandaging for patients with venous insufficiency or who are morbidly obese.

Quantitative trait locus mapping identifies a locus linked to striatal dopamine and points to collagen IV alpha-6 chain as a novel regulator of striatal axonal branching in mice.

Dopaminergic neurons (DA neurons) are controlled by multiple factors, many involved in neurological disease. Parkinson's disease motor symptoms are caused by the demise of nigral DA neurons, leading to loss of striatal dopamine (DA). Here, we measured DA concentration in the dorsal striatum of 32 members of Collaborative Cross (CC) family and their eight founder strains. Striatal DA varied greatly in founders, and differences were highly heritable in the inbred CC progeny. We identified a locus, containing 164 genes, linked to DA concentration in the dorsal striatum on chromosome X. We used RNAseq profiling of the ventral midbrain of two founders with substantial difference in striatal DA-C56BL/6 J and A/J-to highlight potential protein-coding candidates modulating this trait. Among the five differentially expressed genes within the locus, we found that the gene coding for the collagen IV alpha 6 chain (Col4a6) was expressed nine times less in A/J than in C57BL/6J. Using single cell RNA-seq data from developing human midbrain, we found that COL4A6 is highly expressed in radial glia-like cells and neuronal progenitors, indicating a role in neuronal development. Collagen IV alpha-6 chain (COL4A6) controls axogenesis in simple model organisms. Consistent with these findings, A/J mice had less striatal axonal branching than C57BL/6J mice. We tentatively conclude that DA concentration and axonal branching in dorsal striatum are modulated by COL4A6, possibly during development. Our study shows that genetic mapping based on an easily measured Central Nervous System (CNS) trait, using the CC population, combined with follow-up observations, can parse heritability of such a trait, and nominate novel functions for commonly expressed proteins.

Development of the Lymphoedema Patient Reported Outcome Measure (LYMPROM).

To ensure lymphoedema patients in Wales receive the right care, at the right time, by the right person, patient-reported outcome measures (PROMs) were routinely completed within the All-Wales lymphoedema assessment documentation. This evaluation describes the development of the Lymphoedema Patient Reported Outcome Measure (LYMPROM), which is a tool developed by Lymphoedema Network Wales clinicians and key stakeholders. The tool was explored for face, form and content validity during 3 months in 2019; 128 anonymised completions of LYMPROM were reviewed to establish feasibility, acceptability and internal validity using Cronbach's alpha. LYMPROM was feasible and acceptability was high. Face and content validity were reported (i-CVI [item content validity index] range=0.43 - 1; s-CVI/Ave=0.94) and internal consistency was excellent (0.958). LYMPROM was easily integrated within lymphoedema services in Wales, promoting patient-led care and supporting value-based health care. Further evaluations of reliability and validity of LYMPROM are proceeding along with digital integration.

The education needs of health professionals conservatively managing genital oedema: UK survey findings.

BACKGROUND: Adults and children report genital oedema but prevalence is unknown. Pre-registration nurse training rarely includes genital oedema and postgraduate training opportunities are rare. AIM: To identify the education needs of health professionals regarding management of genital oedema. METHOD: An electronic survey was cascaded to health professionals through relevant professional groups and social media. FINDINGS: Of 149 UK respondents, most manage patients with genital oedema but only 2% felt current training was sufficient. Of 138 responding regarding supplemental training, only a half had completed genital oedema specific education, usually of 1-4 hours' duration. Confidence in knowledge was up to 22.5% higher in those with genital oedema education, even accounting for years of experience. The most common top three individual needs were compression, contemporary surgical and medical management and patient assessment. Educational resources are needed and both offline and online formats were suggested; collaborative events with urology/pelvic health are essential. CONCLUSION: Health professionals working in lymphoedema care have (unmet) specific education needs regarding genital oedema management. The desire for both offline and online resources reflects the necessity of accessing learning at a distance and on an 'as needed' basis.

Breast cancer-related upper limb lymphoedema: an overview.

Breast cancer-related lymphoedema can be commonly encountered within a community nurse's role. The severity of lymphoedema can range considerably, from those who are considered 'at risk' due to breast cancer treatment, to individuals with highly complex oedema from advanced disease. This article provides an overview of breast cancer-related lymphoedema, including the risk factors for developing lymphoedema and the impact lymphoedema has physically, psychologically and socially. The treatments for lymphoedema, including clinical practical advice and skills, are presented to support ongoing personal development. A collaborative approach between community nurses and lymphoedema clinics is recommended to ensure that patients receive the best care possible.

Guidelines for managing people with lymphoedema remotely: a post-COVID-19 response document.

During the COVID-19 pandemic it was initially not possible to see people with lymphoedema face-to-face at lymphoedema services, due to the potential risks of the virus, because they were shielding, because of redeployment of rooms or staff, and due to sporadic restrictions of movement. The pandemic therefore accelerated adjustments in lymphoedema service delivery, while ensuring effective and efficient care was paramount. This document presents a pragmatic guide for lymphoedema services. Although clinical and non-clinical staff need to comply with guidance from their own organisations/commissioners, this document aims to provide specific guidance and share good practice in relation to lymphoedema management. These guidelines are based on analysis of the national response of Lymphoedema Network Wales during the first few months of the COVID-19 pandemic and incorporate supporting contemporary advice. They have been used throughout NHS Wales, providing a standardised approach in supporting care for people with lymphoedema. In light of the enduring nature of COVID-19, it is imperative that lymphoedema services have a means to provide suitable care for patients. Although face-to-face appointments are sometimes deemed necessary, many patients can be suitably supported via telehealth consultations. These guidelines may help lymphoedema services restore and reset in a safe and acceptable manner.

Pituitary Tumor Transforming Gene 1 Orchestrates Gene Regulatory Variation in Mouse Ventral Midbrain During Aging.

Dopaminergic neurons in the midbrain are of particular interest due to their role in diseases such as Parkinson's disease and schizophrenia. Genetic variation between individuals can affect the integrity and function of dopaminergic neurons but the DNA variants and molecular cascades modulating dopaminergic neurons and other cells types of ventral midbrain remain poorly defined. Three genetically diverse inbred mouse strains - C57BL/6J, A/J, and DBA/2J - differ significantly in their genomes (∼7 million variants), motor and cognitive behavior, and susceptibility to neurotoxins. To further dissect the underlying molecular networks responsible for these variable phenotypes, we generated RNA-seq and ChIP-seq data from ventral midbrains of the 3 mouse strains. We defined 1000-1200 transcripts that are differentially expressed among them. These widespread differences may be due to altered activity or expression of upstream transcription factors. Interestingly, transcription factors were significantly underrepresented among the differentially expressed genes, and only one transcription factor, Pttg1, showed significant differences between all three strains. The changes in Pttg1 expression were accompanied by consistent alterations in histone H3 lysine 4 trimethylation at Pttg1 transcription start site. The ventral midbrain transcriptome of 3-month-old C57BL/6J congenic Pttg1-/- mutants was only modestly altered, but shifted toward that of A/J and DBA/2J in 9-month-old mice. Principle component analysis (PCA) identified the genes underlying the transcriptome shift and deconvolution of these bulk RNA-seq changes using midbrain single cell RNA-seq data suggested that the changes were occurring in several different cell types, including neurons, oligodendrocytes, and astrocytes. Taken together, our results show that Pttg1 contributes to gene regulatory variation between mouse strains and influences mouse midbrain transcriptome during aging.

Severe lower limb lymphoedema successfully treated with a two-stage debulking procedure: a case report.

Lymphoedema is a chronic condition that has significant functional and psychosocial morbidity. We report a case of severe lower limb lymphoedema successfully treated with a two-stage debulking procedure, highlighting the significant improvements in function and quality of life this operation can have with the appropriate multidisciplinary support.

The benefits of raising awareness of lymphoedema among care home staff.

BACKGROUND: Patients with lymphoedema referred to a lymphoedema service from care homes in one health board area in Wales were often complex cases, with repeated cellulitis, a history of falls and other complications. A pilot project was initiated to develop education and raise awareness of lymphoedema among care home staff. AIMS: To enable care staff to identify residents with lymphoedema, promote prompt referrals, raise the importance of skin care and exercise in the management of lymphoedema and estimate the likely costs from complications associated with lymphoedema. METHODS: An education tool was developed and 47 care homes were asked to participate. A lymphoedema therapist carried out a scoping review of the residents. RESULTS: Forty-four care homes agreed to participate in the project with 1216 education packs being issued to care home staff. Initial findings suggest that of the 960 residents reviewed, 262 had lymphoedema (27%); 4% suffered with frequent falls, 1% had wounds and 3% had recurrent cellulitis. Only 13% (35/262) of residents with lymphoedema were known to the local lymphoedema service. Of the 31 residents reporting cellulitis, 81% had lymphoedema; of the 11 residents identified with a wound, 100% had lymphoedema and of the 40 residents reporting falls, 70% had lymphoedema. CONCLUSION: This educational project has identified the value of raising awareness of lymphoedema within care homes.

Exploring the impact of lymphoedema on individuals and if lymphatic venous anastomosis surgery effects perceptions on quality of life: A qualitative study.

PURPOSE: Lymphoedema is a chronic condition, a cancer consequence and causes physical, psychological, and social implications. A new super-micro surgical treatment Lymphatic Venous Anastomosis (LVA) may improve the symptoms of lymphoedema. This study aims to explore the impact of lymphoedema on individuals and if LVA Surgery changes perceptions on quality of life. METHOD: Semi-structured interviews were conducted with sixteen individual's pre-LVA surgery and repeated six months later post-LVA with ten of the participants. Transcripts were analysed using thematic analysis. RESULTS: Themes identified pre-LVA included: Impact of Living with Lymphoedema, Being Different, and Future Hopes and Emotions. Participants reported making significant changes to 'normal' life due to living with lymphoedema. Changes included alteration in shopping, cleaning, hobbies, familial roles, employment and sexual intimacy. The wearing of compression garments engendered feelings of being unattractive. Themes found post-LVA were: I am one of the Lucky Ones and Returning to Former Self. Post-LVA, participants described how life had become more normalised with fear and apprehension of developing cellulitis reduced. Positive changes had enabled usual activities of daily living to recommence. Some participants had decreased pain, aching, heaviness, stiffness and were wearing their compression garments less. CONCLUSION: The findings suggest that the real impact of living with lymphoedema is much more challenging than previously identified. The findings suggest that LVA can give a future of greater choice for some of its recipients, but further research should explore longer-term benefits. LVA could offer hope to some people with lymphoedema, but a realistic expectation is essential.