Heart of England: HEFT Repository
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Endoscopic remission assessed with PICaSSO virtual electronic chromendoscopy accurately predicts clinical outcomes in ulcerative colitis.
No full textBACKGROUND AND AIMS
A composite endoscopic-histologic remission is increasingly explored as an important endpoint in ulcerative colitis (UC). We investigated combined endoscopic-histologic remission for predicting clinical outcomes at 12 months compared with endoscopic remission alone using the high definition virtual chromoendoscopy (VCE) Paddington International virtual ChromoendoScopy ScOre (PICaSSO) and histology scores.
METHODS
Ulcerative colitis patients, prospectively enrolled from 11 international centres, underwent VCE with targeted biopsies and followed up for 12 months. Endoscopic activity was assessed by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index Severity (UCEIS) followed by VCE-PICaSSO. Robarts Histopathological Index|Robarts Histological index≤3 without neutrophils in mucosa, and Nancy Histological index (NHI)≤ 1 were used to define histologic remission. Combined endoscopic-histologic remission was compared with endoscopic remission alone by Cox proportional hazards model and by two- and three-proportion analysis using pre-specified clinical outcomes.
RESULTS
307 patients were recruited and 302 analysed. There was no difference in survival without specified clinical outcomes between PICaSSO defined endoscopic remission alone and endoscopic plus histologic remission in the rectum (HR 0.42, 95%CI 0.16-1.11 and HR 1.03, 95%CI 0.42-2.52 for Robarts Histological index and NHI respectively) at 12 months. There was however a significant survival advantage without specified clinical outcome events for UCEIS combined with histology compared with UCEIS alone (HR 0.30, 95%CI 0.12-0.75, p = 0.02) at 12 months (but not combined with NHI). For MES there was no advantage for predicting specified clinical outcomes at 12 months for endoscopy alone versus endoscopy plus histology, but there were differences in two and three proportion analysis at 6 months.
CONCLUSION
Endoscopic remission by VCE-PICaSSO alone was similar to combined endoscopic and histologic remission for predicting specified clinical outcomes at 12 months. Larger studies with specific therapeutic interventions are required to further confirm the findings
Do entrapment, injuries, outcomes and potential for self-extrication vary with age? A pre-specified analysis of the UK trauma registry (TARN).
No full textBACKGROUND
Motor vehicle collisions (MVCs), particularly those associated with entrapment, are a common cause of major trauma. Current extrication methods are focused on spinal movement minimisation and mitigation, but for many patients self-extrication may be an appropriate alternative. Older drivers and passengers are increasingly injured in MVCs and may be at an increased risk of entrapment and its deleterious effects. The aim of this study is to describe the injuries, trapped status, outcomes, and potential for self-extrication for patients following an MVC across a range of age groups.
METHODS
This is a retrospective study using the Trauma Audit and Research Network (TARN) database. Patients were included if they were admitted to an English hospital following an MVC from 2012 to 2019. Patients were excluded when their outcomes were not known or if they were secondary transfers. Simple descriptive analysis was used across the age groups: 16-59, 60-69, 70-79 and 80+ years. Logistic regression was performed to develop a model with known confounders, considering the odds of death by age group, and examining any interaction between age and trapped status with mortality.
RESULTS
70,027 patients met the inclusion criteria. Older patients were more likely to be trapped and to die following an MVC (p < 0.0001). Head, abdominal and limb injuries were more common in the young with thoracic and spinal injuries being more common in older patients (all p < 0.0001). No statistical difference was found between the age groups in relation to ability to self-extricate. After adjustment for confounders, the 80 + age group were more likely to die if they were trapped; adjusted OR trapped 30.2 (19.8-46), not trapped 24.2 (20.1-29.2).
CONCLUSIONS
Patients over the age of 80 are more likely to die when trapped following an MVC. Self-extrication should be considered the primary route of egress for patients of all ages unless it is clearly impracticable or unachievable. For those patients who cannot self-extricate, a minimally invasive extrication approach should be employed to minimise entrapment time
Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.
No full textProgress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p 4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans
Correction: Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.
No full textShorter Treatment for Nonsevere Tuberculosis in African and Indian Children.
No full textBACKGROUND
Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.
METHODS
We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.
RESULTS
From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups).
CONCLUSIONS
Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.)
Concurrent development of encapsulating peritoneal sclerosis and calciphylaxis in a patient with peritoneal dialysis for end-stage renal disease.
No full textBoth encapsulating peritoneal sclerosis (EPS) and calciphylaxis are rare but severe complications involving patients with end-stage renal disease. In this report, we discuss a unique case of a 73-year-old female patient who had undergone 8 years of peritoneal dialysis for IgA nephropathy and concurrently developed these two synchronous complications within 3 months of each other. Diagnosis and management of both conditions were discussed in detail as well as the possible association between the two. With surgical treatment for EPS and measures to minimise bone mineral disorder abnormalities, both complications have been successfully managed to date
UK clinical guideline for the prevention and treatment of osteoporosis.
No full textThe National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management.
INTRODUCTION
The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older.
METHODS
Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence.
RESULTS
Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement.
CONCLUSION
The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases
A retrospective real-world study of the current treatment pathways for myelofibrosis in the United Kingdom: the REALISM UK study.
No full textBackground
Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom.
Methods
The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment.
Discussion
Two hundred patients were included (63% [ = 126/200] with primary MF; 37% [ = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. 'Watch and wait' was the first management strategy for 53.5% ( = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0-350); patients with higher risk disease were prescribed active treatment sooner.
Conclusion
These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients.
Plain Language Summary
Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient's daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently. We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK. The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was 'watch and wait', which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner. The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives