Background: The 2018 Scottish GP contract established GP Clusters and multidisciplinary team (MDT) expansion. Qualitative studies have suggested sub-optimal progress.
Aim: To quantify progress since the introduction of the new contract.
Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mismatch repair proteins (dMMR). Neoplasms with mismatch repair deficiency often have high tumor mutational burden (TMB-High). MSI-High, dMMR, and TMB-High are all histology agnostic biomarkers for potential therapy using immune checkpoint inhibitors (ICI).
View Article and Find Full Text PDFAdvances in myeloma have resulted in improved prognosis for patients. However complications of the disease and treatment, pose a risk of specific long-term consequences. An audit tool was adapted to assess adherence to the British Society for Haematology guidelines for screening and management of long-term myeloma consequences.
View Article and Find Full Text PDFThe availability and integration of electrophysiological and molecular data from the living brain is critical to understand and diagnose complex human disease. Intracranial stereo electroencephalography (SEEG) electrodes used for identifying the seizure focus on epilepsy patients could enable the integration of such multimodal data. Here, we report MoPEDE (Multimodal Profiling of Epileptic Brain Activity via Explanted Depth Electrodes), a method that recovers extensive protein-coding transcripts, including cell-type markers, DNA methylation and short variant profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function.
View Article and Find Full Text PDFPurpose: Psychological safety is critical for fostering well-being. Integral to the mission of academic institutions, trainees are among the most vulnerable to negative workplace experiences, calling for a need to understand factors that contribute to psychological safety in this population. Our objective is to empirically explore trainee psychological safety to inform best practices for training environments.
View Article and Find Full Text PDFIntroduction: Multidisciplinary care (MDC) for late-stage chronic kidney disease (CKD) has been associated with improved patient outcomes compared with traditional nephrology care; however, the optimal MDC model is unknown. In 2015, we implemented a novel MDC model for patients with late-stage CKD informed by the Chronic Care Model conceptual framework, including an expanded MDC team, care plan meetings, clinical risk prediction, and a patient dashboard.
Methods: We conducted a single-center, retrospective cohort study of adults with late-stage CKD (estimated glomerular filtration rate [eGFR] < 30 ml/min per 1.
Introduction: Invasive lobular carcinoma (ILC) contributes significantly to the global cancer burden and is the most common of the histological "special types" of breast cancer. ILC has unique features setting it apart from the more common invasive ductal carcinoma (IDC). Despite differences, treatment algorithms do not consider histological differences.
View Article and Find Full Text PDFBackground: In clinical practice, internal fixation (IF) is a commonly utilized technique for metastatic bone disease (MBD) to the distal femur. Additionally, distal femoral reconstruction (DFR) has shown to be an effective surgical technique for primary tumors and MBD in the distal femur. The existing body of research comparing these methods has not focused on MBD or pathological fractures and thus does not guide surgical approach in the case of distal femoral MBD.
View Article and Find Full Text PDFGene promoters filter transcription factor (TF) localization dynamics and changes in the DNA binding affinity of TFs. Here, we present a protocol to probe how promoters decode TF dynamics in Saccharomyces cerevisiae by combining optogenetic control with microscopy. We describe steps for preparing and characterizing a light delivery platform and light-controlled TF mutants.
View Article and Find Full Text PDFUnlabelled: The purine nucleotides ATP and GTP are made from the common precursor inosine monophosphate (IMP). Maintaining the correct balance of these nucleotides for optimal cell growth is controlled in part by the enzyme IMP dehydrogenase (IMPDH), which catalyzes the first dedicated step of GTP biosynthesis. The regulation of IMPDH mRNA and protein levels in the yeast grown in liquid culture has been studied in some detail, but regulation of IMPDH protein under conditions of cellular crowding on a solid substrate has not been examined.
View Article and Find Full Text PDFObjective: The aims of this scoping review were to summarize the evidence regarding sex, racial, ethnic, geographic, and socioeconomic disparities in post-acute rehabilitation following total hip arthroplasty (THA) and knee arthroplasty (TKA).
Methods: Literature searches were conducted in Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and PEDro. Studies were included if they were original research articles published 1993 or later; used data from the US; included patients after THA and/or TKA; presented results according to relevant sociodemographic variables, including sex, race, ethnicity, geography, or socioeconomic status; and studied the utilization of post-acute rehabilitation as an outcome.
Introduction: Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC.
Methods: PubMed, EMBASE and Web of Science were searched as part of our review.
Background: Expanding primary care multidisciplinary teams (MDTs) was a key component of the 2018 Scottish GP contract, with more than 4700 MDT staff appointed since then.
Aim: To explore patients' views on primary care MDT expansion in Scotland.
Design & Setting: A mixed-methods evaluation, which included a postal survey and semi-structured telephone interviews with patients in Scotland.
Background: Workplace social isolation and loneliness have been found to result in a decline in job satisfaction and an increase in burnout among working individuals. The COVID-19 pandemic exacerbated feelings of loneliness and social isolation among healthcare workers. The majority of research on healthcare worker experiences is conducted in siloes which does not reflect the shared experiences of interprofessional teams.
View Article and Find Full Text PDFWith escape games gaining in popularity, we decided to adapt the concept of an existing medical escape game to the needs of our family medicine residents, by simulating clinical situations and creating puzzles with medical content. This activity was a fun way to integrate theoretical learning while developing a number of CanMEDS roles. Overall, the residents were very satisfied with the topics chosen and the interactive aspect of the experience.
View Article and Find Full Text PDFObjective: The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy.
Methods: Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy.
Objective: Here we report our preclinical, proof-of-concept testing to assess the ability of a novel device to correct mitral regurgitation. The Milwaukee Heart device aims to enable any cardiac surgeon to perform high-quality mitral valve repair using a standard annuloplasty ring with a crosshatch of microporous, monofilament suture.
Methods: Hemodynamic, echocardiographic, and videographic data were collected at baseline, following induction of mitral regurgitation, and after repair using porcine hearts in an ex vivo biosimulator model.
Purpose: The recent findings from the DESTINY-Breast04 trial highlighted the clinical importance of distinguishing between HER2 immunohistochemistry (IHC) scores 0 and 1 + in metastatic breast cancer (BC). However, pathologist interpretation of HER2 IHC scoring is subjective, and standardized methodology is needed. We evaluated the consistency of HER2 IHC scoring among pathologists and the accuracy of digital image analysis (DIA) in interpreting HER2 IHC staining in cases of HER2-low BC.
View Article and Find Full Text PDFBrepocitinib is an oral selective dual TYK2/JAK1 inhibitor and based on its cytokine inhibition profile is expected to provide therapeutic benefit in the treatment of plaque psoriasis. Efficacy data from a completed Phase 2a study in patients with moderate-to-severe plaque psoriasis were utilized to develop a population exposure-response model that can be employed to inform dose selection decisions for further clinical development. A modeling approach that employs the zero-inflated beta distribution was used to account for the bounded nature and distributional characteristics of the Psoriasis Area and Severity Index (PASI) score data.
View Article and Find Full Text PDFThe presence of large protein inclusions is a hallmark of neurodegeneration, and yet the precise molecular factors that contribute to their formation remain poorly understood. Screens using aggregation-prone proteins have commonly relied on downstream toxicity as a readout rather than the direct formation of aggregates. Here, we combined a genome-wide CRISPR knockout screen with Pulse Shape Analysis, a FACS-based method for inclusion detection, to identify direct modifiers of TDP-43 aggregation in human cells.
View Article and Find Full Text PDFHere, we establish a CT-radiomics based method for application in invasive, orthotopic rodent brain tumour models. Twenty four NOD/SCID mice were implanted with U87R-Luc2 GBM cells and longitudinally imaged via contrast enhanced (CE-CT) imaging. Pyradiomics was employed to extract CT-radiomic features from the tumour-implanted hemisphere and non-tumour-implanted hemisphere of acquired CT-scans.
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