Cheshire Wirral Partnership - Research Conference

The presentation, experiential workshop and exhibition for 100 health practitioners took place at an annual event which shares good practice across the Cheshire Wirral Partnership (CWP) NHS Trust. The highly innovative ComMA research programme was nominated by CWP for a recognition award and shortlisted for the Outstanding Contribution to Research Development and Innovation. The presentation and experiential workshop explained how patients and artists together explored sexual problems encountered following cancer treatment. This novel and highly collaborative approach empowered patients to use art and new forms of artistic expression as an alternative language to express and communicate their feelings of emotional and physical trauma using visual metaphors. ComMA enabled patients to explore and express their feelings through the use of collage and drawing on items such as gowns, which had a deep meaning in the context of their treatment, to enable them to express their feelings and to seek appropriate support. Work co-produced by the artists and patients was shared at the workshop to allow health professionals to understand these issues from a patient’s perspective

FARMACOTERAPIA DO PACIENTE IDOSO.

RESUMO  O envelhecimento populacional está relacionado ao maior adoecimento e consequente uso de medicamentos. Ao acumular diagnósticos e doenças, por vezes o idoso está sujeito à polifarmácia, que aumenta o risco em até sete vezes do uso de medicamento potencialmente inapropriado ao idoso. Essa população devido ao processo natural de envelhecimento tem suas funções biológicas alteradas, afetando sua farmacocinética e farmacodinâmica. As diversas alterações aumentam o risco de reações adversas, que aliadas às interações medicamentosas aumentam o risco de internações hospitalares e da morbimortalidade. Para diminuição destes eventos, foram criados diversas ferramentas para avaliação dos medicamentos potencialmente inapropriados ao idoso, dentre eles o Critério de Beers, sendo a ferramenta mais utilizada no Brasil. Descritores: Idoso, Medicamento potencialmente inapropriado ao idoso e Polifarmácia   PHARMACOTHERAPY IN ELDERLY   ABSTRACT Population aging is related to greater illness and consequent use of medicines. By accumulating diagnoses and diseases, sometimes the elderly are subject to polypharmacy, which increases the risk of up to seven times the use of potentially inappropriate medication for the elderly. This population due to the natural aging process has its biological functions altered, affecting its pharmacokinetics and pharmacodynamics. The various changes increase the risk of adverse reactions, which combined with drug interactions increase the risk of hospitalizations and morbidity and mortality. To reduce these events, several tools were created to evaluate potentially inappropriate drugs for the elderly, including the Beers Criterion, being the most used tool in Brazil. Key-words: Elderly AND potentially inappropriate medications AND AND polypharmacy

Delineation of Cohen Syndrome Following a Large-Scale Genotype-Phenotype Screen

Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The pleiotropic phenotype, combined with insufficient clinical data, often leads to an erroneous diagnosis and has led to confusion in the literature. Here, we report the results of a comprehensive genotype-phenotype study on the largest cohort of patients with Cohen syndrome assembled to date. We found 22 different COH1 mutations, of which 19 are novel, in probands identified by our diagnostic criteria. In addition, we identified another three novel mutations in patients with incomplete clinical data. By contrast, no COH1 mutations were found in patients with a provisional diagnosis of Cohen syndrome who did not fulfill the diagnostic criteria (“Cohen-like” syndrome). This study provides a molecular confirmation of the clinical phenotype associated with Cohen syndrome and provides a basis for laboratory screening that will be valuable in its diagnosis

Perfil cognitivo e associações entre idosos longevos em contexto ambulatorial no Distrito Federal

Objetivou investigar associações entre o declínio cognitivo de idosos longevos em contexto ambulatorial e variáveis sociodemográficas, desempenho funcional, doenças crônicas, número de hospitalizações e acesso aos serviços de saúde. Foram entrevistados idosos longevos (80 anos e mais) residentes no Distrito Federal, avaliados em contexto ambulatorial por questionários padronizados e pelo Miniexame do Estado Mental (MEEM). Nas análises bivariadas, o declínio cognitivo esteve associado à faixa etária (85 anos e mais), possuir uma ou mais limitações nas atividades básicas de vida diária (ABVD), residir em arranjos domiciliares bi e trigeracionais e ter maior número de hospitalizações no último ano. No modelo logístico múltiplo, permaneceram associados ao declínio cognitivo em longevos as ABVD e as hospitalizações no último ano. Por tratar-se de uma população com maior demanda assistencial de saúde, torna-se necessário delinear medidas de prevenção e a promoção de cuidados de longa duração

Evidence for a Causal Role for \u3ci\u3eEscherichia coli\u3c/i\u3e Strains Identified as Adherent-Invasive (AIEC) in Intestinal Inflammation

Enrichment of adherent-invasive Escherichia coli (AIEC) has been consistently detected in subsets of inflammatory bowel disease (IBD) patients. Although some AIEC strains cause colitis in animal models, these studies did not systematically compare AIEC with non-AIEC strains, and causal links between AIEC and disease are still disputed. Specifically, it remains unclear whether AIEC shows enhanced pathogenicity compared to that of commensal E. coli found in the same ecological microhabitat and if the in vitro phenotypes used to classify strains as AIEC are pathologically relevant. Here, we utilized in vitro phenotyping and a murine model of intestinal inflammation to systematically compare strains identified as AIEC with those identified as non-AIEC and relate AIEC phenotypes to pathogenicity. Strains identified as AIEC caused, on average, more severe intestinal inflammation. Intracellular survival/replication phenotypes routinely used to classify AIEC positively correlated with disease, while adherence to epithelial cells and tumor necrosis factor alpha production by macrophages did not. This knowledge was then applied to design and test a strategy to prevent inflammation by selecting E. coli strains that adhered to epithelial cells but poorly survived/replicated intracellularly. Two E. coli strains that ameliorated AIEC-mediated disease were subsequently identified. In summary, our results show a relationship between intracellular survival/replication in E. coli and pathology in murine colitis, suggesting that strains possessing these phenotypes might not only become enriched in human IBD but also contribute to disease. We provide new evidence that specific AIEC phenotypes are pathologically relevant and proof of principle that such mechanistic information can be therapeutically exploited to alleviate intestinal inflammation

Bristol advisory committee on climate change: One City climate strategy progress review - February 2023

This report from the Bristol Advisory Committee on Climate Change (BACCC) reviews citywide progress on tackling the climate crisis and concludes that, although there is some positive progress, the city is still way off meeting its 2030 carbon neutral and climate resilient targets.BACCC is an independent committee which provides expert advice on reducing greenhouse gas emissions and adapting to the impacts of a changing climate. Their latest report is an assessment of progress against the One City Climate Strategy which was launched by the Environment Board in March 2020, setting out the pathway for the city to reduce carbon emissions and build resilience to a changing climate by 2030

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract: Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Workshop: Guided Exercises and Sharing

A series of guided exercises and sharing