5366 research outputs found
Sort by
Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation.
No full textOBJECTIVE
To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved.
BACKGROUND
Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need.
METHODS
A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months.
RESULTS
Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients).
CONCLUSIONS
This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target
British Society for Haematology guidelines for the management of adult myelodysplastic syndromes.
No full textRadiomics Analysis Derived From LGE-MRI Predict Sudden Cardiac Death in Participants With Hypertrophic Cardiomyopathy.
No full textTo identify significant radiomics features derived from late gadolinium enhancement (LGE) images in participants with hypertrophic cardiomyopathy (HCM) and assess their prognostic value in predicting sudden cardiac death (SCD) endpoint. The 157 radiomic features of 379 sequential participants with HCM who underwent cardiovascular magnetic resonance imaging (MRI) were extracted. CoxNet (Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net) and Random Forest models were applied to optimize feature selection for the SCD risk prediction and cross-validation was performed. During a median follow-up of 29 months (interquartile range, 20-42 months), 27 participants with HCM experienced SCD events. Cox analysis revealed that two selected features, local binary patterns (LBP) (19) (hazard ratio (HR), 1.028, 95% CI: 1.032-1.134; = 0.001) and Moment (1) (HR, 1.212, 95%CI: 1.032-1.423; = 0.02) provided significant prognostic value to predict the SCD endpoints after adjustment for the clinical risk predictors and late gadolinium enhancement. Furthermore, the univariately significant risk predictor was improved by the addition of the selected radiomics features, LBP (19) and Moment (1), to predict SCD events ( < 0.05). The radiomics features of LBP (19) and Moment (1) extracted from LGE images, reflecting scar heterogeneity, have independent prognostic value in identifying high SCD risk patients with HCM
Experience of orbital floor fractures in a UK level one trauma centre: a focus on the surgical approach and lid-related complications.
No full textThe two surgical approaches to access orbital fractures are transconjunctival and transcutaneous. The aim of this study was to assess the outcomes of orbital repairs with a focus on lid-related complications and their management. A retrospective analysis was carried out over a five-year period (January 2015 to January 2020) to assess all consecutive orbital repairs in our unit. Data were collected for variables including demographics, fracture pattern, surgical approach, and details of postoperative complications. A total of 111 patients were included in the study, 94 were male (85%), the majority being between 16 and 45 years of age. A total of 46 (41%) had isolated orbital floor fractures, 31 (28%) zygomaticomaxillary complex, and 18 (16%) Le Fort pattern fractures. Eighty per cent (n = 91) received a transconjunctival approach as first choice. In the transconjunctival group, six (6.6%) had entropion and increased scleral show, four (4.4%) had ectropion, and none had canthal malposition. In the transcutaneous group (n = 20) there was a higher rate of ectropion (25%, n = 5), a lower rate of entropion (n = 1, 5%) and higher rate of increased scleral show (n = 2, 10%). Factors associated with a higher rate of complications included complex fractures, use of conjunctival sutures, and increased length of time to surgery. Seventy-two per cent of patients who suffered entropion required further surgical treatment. The most common complication of the transconjunctival approach was entropion, and clinicians should have a low threshold for early surgical management. We feel that this should be part of the consenting process, especially in high-risk cases
The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality.
No full textHost Immune-Metabolic Adaptations Upon Mycobacterial Infections and Associated Co-Morbidities.
No full textMycobacterial diseases are a major public health challenge. Their causative agents include, in order of impact, members of the complex (causing tuberculosis), (causing leprosy), and non-tuberculous mycobacterial pathogens including Macrophages are mycobacterial targets and they play an essential role in the host immune response to mycobacteria. This review aims to provide a comprehensive understanding of the immune-metabolic adaptations of the macrophage to mycobacterial infections. This metabolic rewiring involves changes in glycolysis and oxidative metabolism, as well as in the use of fatty acids and that of metals such as iron, zinc and copper. The macrophage metabolic adaptations result in changes in intracellular metabolites, which can post-translationally modify proteins including histones, with potential for shaping the epigenetic landscape. This review will also cover how critical tuberculosis co-morbidities such as smoking, diabetes and HIV infection shape host metabolic responses and impact disease outcome. Finally, we will explore how the immune-metabolic knowledge gained in the last decades can be harnessed towards the design of novel diagnostic and therapeutic tools, as well as vaccines
COVID-19: Effect on gastroenterology and hepatology service provision and training: Lessons learnt and planning for the future.
No full textIn late 2019, reports arose of a new respiratory disease in China, identified as a novel coronavirus, severe acute respiratory syndrome coronavirus 2. The World Health Organisation named the disease caused by the virus 'coronavirus disease 2019 (COVID-19)'. It was declared a pandemic in early 2020, after the disease rapidly spread across the world. COVID-19 has not only resulted in substantial morbidity and mortality but also significantly impacted healthcare service provision and training across all medical specialties with gastroenterology and Hepatology services being no exception. Internationally, most, if not all 'non-urgent' services have been placed on hold during surges of infections. As a result there have been delayed diagnoses, procedures, and surgeries which will undoubtedly result in increased morbidity and mortality. Outpatient services have been converted to remote consultations where possible in many countries. Trainees have been redeployed to help care for COVID-19 patients in other settings, resulting in disruption to their training - particularly endoscopy and outpatient clinics. This has led to significant anxiety amongst trainees, and risks prolongation of training. It is of the utmost importance to develop strategies that continue to support COVID-19-related service provision, whilst also supporting existing and future gastroenterology and Hepatology services and training. Changes to healthcare provision during the pandemic have generated new and improved frameworks of service and training delivery, which can be adopted in the post-COVID-19 world, leading to enhanced patient care
The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study.
No full textProthrombin induced by vitamin K absence II (PIVKA-II) has recently been validated internationally as a diagnostic biomarker for hepatocellular carcinoma (HCC), as part of the GALAD model. However, its role as a treatment response biomarker has been less well explored. We, therefore, undertook a prospective study at a tertiary centre in the UK to evaluate the role of PIVKA-II as a treatment response biomarker in patients with early, intermediate and advanced stage HCC. In a cohort of 141 patients, we found that PIVKA-II levels tracked concordantly with treatment response in the majority of patients, across a range of different treatment modalities. We also found that rises in PIVKA-II levels almost always predated radiological progression. Among AFP non-secretors, PIVKA-II was found to be informative in 60% of cases. In a small cohort of patients undergoing liver transplantation, pre-transplant PIVKA-II levels predicted for microvascular invasion and poorer differentiation. Our results demonstrate the potential utility of PIVKA-II as a treatment response biomarker and in predicting microvascular invasion, in a Western population. PIVKA-II demonstrated improved performance over AFP but, as a single biomarker, its performance was still limited. Further larger prospective studies are recommended to evaluate PIVKA-II as a treatment response biomarker, within the GALAD model
The impact of COVID-19 on the wellbeing of the UK nursing and midwifery workforce during the first pandemic wave: A longitudinal survey study.
No full textBACKGROUND
The specific challenges experienced by the nursing and midwifery workforce in previous pandemics have exacerbated pre-existing professional and personal challenges, and triggered new issues. We aimed to determine the psychological impact of the COVID-19 pandemic on the UK nursing and midwifery workforce and identify potential factors associated with signs of post-traumatic stress disorder.
METHODS
A United Kingdom national online survey was conducted at three time-points during the first wave of the COVID-19 pandemic between April and August 2020 (T1 and T2 during initial wave; T3 at three-months following the first wave). All members of the UK registered and unregistered nursing and midwifery workforce were eligible to participate. The survey was promoted via social media and through organisational email and newsletters. The primary outcome was an Impact of Events Scale-Revised score indicative of a post-traumatic stress disorder diagnosis (defined using the cut-off score ≥33). Multivariable logistic regression modelling was used to assess the association between explanatory variables and post-traumatic stress disorder.
RESULTS
We received 7840 eligible responses (T1- 2040; T2- 3638; T3- 2162). Overall, 91.6% participants were female, 77.2% were adult registered nurses, and 28.7% were redeployed during the pandemic. An Impact of Events Scale-Revised score ≥33 (probable post-traumatic stress disorder) was observed in 44.6%, 37.1%, and 29.3% participants at T1, T2, and T3 respectively. At all three time-points, both personal and workplace factors were associated with probable post-traumatic stress disorder, although some specific associations changed over the course of the pandemic. Increased age was associated with reduced probable post-traumatic stress disorder at T1 and T2 (e.g. 41-50 years at T1 odds ratio (OR) 0.60, 95% confidence interval (CI) 0.42-0.86), but not at T3. Similarly, redeployment with inadequate/ no training was associated with increased probable post-traumatic stress disorder at T1 and T2, but not at T3 (T1 OR 1.37, 95% CI 1.06-1.77; T3 OR 1.17, 95% CI 0.89-1.55). A lack of confidence in infection prevention and control training was associated with increased probable post-traumatic stress disorder at all three time-points (e.g. T1 OR 1.48, 95% CI 1.11-1.97).
CONCLUSION
A negative psychological impact was evident 3-months following the first wave of the pandemic. Both personal and workplace are associated with adverse psychological effects linked to the COVID-19 pandemic. These findings will inform how healthcare organisations should respond to staff wellbeing needs both during the current pandemic, and in planning for future pandemics
Quantification of Flualprazolam in Blood by LC-MS-MS: A Case Series of Nine Deaths.
No full textThe emergence of novel designer benzodiazepines continues to be a public health concern. Flualprazolam is one of these drugs. It was initially identified in 2017. User forums suggest it is slightly more potent than alprazolam and has longer-lasting central nervous system depressant effects. Here we report a simple, sensitive liquid chromatography-tandem mass spectrometry method for flualprazolam and report a series of nine cases in which flualprazolam was quantified. As is typical of forensic toxicology in the twenty-first century, all the cases had more than one drug present. None of the deaths could be directly attributed to flualprazolam alone, but all were likely due to a combination of sedative drugs. However, this paper still adds to the data available to allow interpretation of postmortem flualprazolam concentrations