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    5366 research outputs found

    Systemic and adipocyte transcriptional and metabolic dysregulation in Idiopathic Intracranial Hypertension.

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    BACKGROUND Idiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess and an increased risk of cardiovascular morbidity. Here we evaluate systemic and adipose specific metabolic determinants of the IIH phenotype. METHODS In fasted, matched IIH (N=97) and control (N=43) patients, we assessed: glucose and insulin homeostasis and leptin levels. Body composition was assessed along with an interrogation of adipose tissue function via nuclear magnetic resonance metabolomics and RNA sequencing in paired omental and subcutaneous biopsies in a case control study. RESULTS We demonstrate an insulin and leptin resistant phenotype in IIH in excess to that driven by obesity. Adiposity in IIH is preferentially centripetal and is associated with increased disease activity and insulin resistance. IIH adipocytes appear transcriptionally and metabolically primed towards depot-specific lipogenesis. CONCLUSIONS These data show that IIH is a metabolic disorder in which adipose tissue dysfunction is a feature of the disease. Managing IIH as a metabolic disease could reduce disease morbidity and improving cardiovascular outcomes. FUNDING This study was supported by the National Institute of Health Research UK (NIHR-CS-011-028), the Medical Research Council UK (MR/K015184/1) and the Midlands Neuroscience Teaching and Research Fund

    The impact of the COVID-19 pandemic on application of European Society of Cardiology (ESC) guidelines for exercise in adults with congenital heart disease: a data-based questionnaire.

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    INTRODUCTION Regular physical activity is safe and effective therapy for adults with congenital heart disease (ACHD) and is recommended by European Society of Cardiology (ESC) guidelines. The COVID-19 pandemic poses enormous challenges to healthcare teams and patients when ensuring guideline compliance. We explored the implications of COVID-19 on physical activity levels in ACHD patients. MATERIALS AND METHODS A data-based questionnaire was distributed to ACHD patients at a regional tertiary centre from October to November 2020. RESULTS Prior to the COVID-19 pandemic, 96 (79.3%) of 125 respondents reported participating in regular physical activity, with 66 (52.8%) meeting target levels (moderate physical activity for at least 150 minutes per week). Commonest motivations for physical activity were general fitness (53.6%), weight loss (36.0%) and mental health benefits (30.4%). During the pandemic, the proportion that met target levels significantly decreased from 52.8% to 40.8% (p=0.03). The commonest reason was fear of COVID-19 (28.0%), followed by loss of motivation (23.2%) and gym/fitness centre closure (15.2%). DISCUSSION The COVID-19 pandemic has negatively impacted exercise levels of ACHD patients. Most do not meet recommended physical activity levels, mainly attributable to fear of COVID-19. Even before the pandemic, only half of respondents met physical activity guidelines. Availability of online classes can positively impact exercise levels so could enhance guideline compliance. This insight into health perceptions and behaviors of ACHD patients may help develop quality improvement initiatives to improve physical activity levels in this population

    Achieving 'Marginal Gains' to Optimise Outcomes in Resectable Pancreatic Cancer.

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    Improving outcomes among patients with resectable pancreatic cancer is one of the greatest challenges of modern medicine. Major improvements in survival will result from the development of novel therapies. However, optimising existing pathways, so that patients realise benefits of already proven treatments, presents a clear opportunity to improve outcomes in the short term. This narrative review will focus on treatments and interventions where there is a clear evidence base to improve outcomes in pancreatic cancer, and where there is also evidence of variation and under-treatment. Avoidance of preoperative biliary drainage, treatment of pancreatic exocrine insufficiency, prehabiliation and enhanced recovery after surgery, reducing perioperative complications, optimising opportunities for elderly patients to receive therapy, optimising adjuvant chemotherapy and regular surveillance after surgery are some of the strategies discussed. Each treatment or pathway change represents an opportunity for marginal gain. Accumulation of marginal gains can result in considerable benefit to patients. Given that these interventions already have evidence base, they can be realised quickly and economically

    Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation-Reply.

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    Management of surgery, menorrhagia and child-birth for patients with unclassified bleeding disorders: a systematic review of cohort studies.

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    Unclassified bleeding disorders account for 2.6% of all new bleeding disorder registrations in the UK. The management of the bleeding phenotype associated with these disorders is poorly described. Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid, desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII, for patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia. We searched for randomized controlled trials in MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science and the Transfusion Evidence Library from inception to 24 February 2020. Wherever appropriate, data were pooled using the metaprop function of STATA. Two studies with 157 participants with unclassified bleeding disorders were identified. The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative tranexamic acid was 11% (95% confidence interval 3--20%; n = 52; I2 = 0%); the risk for desmopressin and tranexamic acid in combination was 3% (95% confidence interval 0--7%; n = 71; I2 = 0%). There were no instances of major bleeding. In one procedure, 1 of 71 (1.4%), treated with a combination of desmopressin and tranexamic acid, the patient had a line-related deep vein thrombosis. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia to draw conclusions. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both tranexamic acid, and the combination of tranexamic and desmopressin have high rates of haemostatic efficacy and have few adverse events. PROTOCOL REGISTRATION PROSPERO CRD42020169727

    Patient perspectives of target weight management and ultrafiltration in haemodialysis: a multi-center survey.

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    BACKGROUND Decisions around planned ultrafiltration volumes are the only part of the haemodialysis prescription decided upon at every session. Removing too much fluid or too little is associated with both acute symptoms and long-term outcomes. The degree to which patients engage with or influence decision-making is not clear. We explored patient perspectives of prescribing ultrafiltration volumes, their understanding of the process and engagement with it. METHODS A questionnaire developed for this study was administered to 1077 patients across 10 UK Renal Units. Factor analysis reduced the dataset into factors representing common themes. Relationships between survey results and factors were investigated using regression models. ANCOVA was used to explore differences between Renal Units. RESULTS Patients generally felt in control of their fluid management and that they were given the final say on planned ultrafiltration volumes. Around half of the respondents reported they take an active role in their treatment. However, respondents were largely unable to relate signs and symptoms to fluid management practice and a third said they would not report common signs and symptoms to clinicians. A fifth of patients reported not to know how ultrafiltration volumes were calculated. Patients responded positively to questions relating to healthcare staff, though with significant variation between units, highlighting differences in perception of care. CONCLUSIONS Despite a lack of formal acknowledgement in fluid management protocols, patients have significant involvement in decisions regarding fluid removal during dialysis. Furthermore, substantial gaps remain in patient knowledge and engagement. Formalizing the role of patients in these decisions, including patient education, may improve prescription and achievement of target weights

    Forewarned is Forearmed: chronic spontaneous urticaria as a potential risk to effective SARS-COV-2 vaccine uptake and global public health.

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    Chronic spontaneous urticaria and angioedema (CSU/A) is a common condition with an estimated global point prevalence of 0.7% (95% C.I, 0.2-1.4)(1), higher in non-White populations. Symptoms present as an 'allergy mimic' but are underpinned by non-specific, non-IgE-mediated mast cell histamine release. The combination of common population prevalence and likelihood of vaccines precipitating symptoms in those with CSU/A presents an immediate risk to the SARS-COV-2 global vaccine program

    Correlation Between Thyroid Fine Needle Aspiration Cytology and Postoperative Histology: A 10-Year Single-Centre Experience.

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    Introduction Fine needle aspiration cytology (FNAC) forms part of the routine workup for suspicious thyroid nodules. Whilst cytological analysis is less precise than histological assessment, it is quick and easy to perform and may avoid the need for invasive and potentially risky surgery. Methods This retrospective study spanned a 10-year period comparing preoperative FNAC with postoperative histology results to establish the accuracy of diagnosis and malignancy rates within our population. These results were then compared to the published figures in the literature. Results The histological reports of 659 consecutive cases of thyroid surgery between 2006 and 2015 were retrieved from our hospital database. Among the 471 patients (71.5%) who underwent preoperative FNAC, the postoperative histology was reported as benign in 352 (74.7%) and malignant in 119 cases (25.3%). Papillary thyroid cancer (PTC) was the commonest histological diagnosis. Thy1 grade was reported in 165 (30%) cases, with 19.4% having a final histological diagnosis of malignancy. In the Thy2 group, 85.3% of patients had a benign final histological diagnosis, while 14.7% had malignancy (false-negative results). Malignancy was found in 89% of Thy4 and 100% of Thy5 group patients.  Conclusions Rates of malignancy varied considerably from those in the published literature. Each centre should be able to quote a local malignancy rate during patient counselling. It is also prudent for all units performing thyroid diagnostics to investigate the factors that might lead to inaccuracies in reporting

    Absence of monitoring in withdrawal of clinically-assisted nutrition and hydration (CANH) and other treatments: a cause for concern?

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    Since 2018, there has been no requirement to bring decisions about the withdrawal of clinically-assisted nutrition and hydration (CANH) in patients with persistent disorders of consciousness before the courts, providing that the requirements of the Mental Capacity Act 2005 (MCA) are fulfilled. Subsequent British Medical Association and Royal College of Physicians guidance on CANH withdrawal recommended standards of record keeping and internal and external audit to ensure local decision making was compliant with the MCA to safeguard patients. The scope of the guidance also included patients with stroke and neurodegenerative disorders.Freedom of Information requests made 2 years after the introduction of this guidance have shown that none of the NHS trusts or clinical commissioning groups who responded were undertaking any systematic monitoring of these decisions. Neither is the Care Quality Commission reviewing these decisions, as there is 'no statutory requirement' to do so. It appears there is a lack of organised scrutiny of these highly complex life-ending treatment decisions. This omission must surely be a cause for concern

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