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A holistic view of mouse enhancer architectures reveals analogous pleiotropic effects and correlation with human disease.
No full textBACKGROUND
Efforts to elucidate the function of enhancers in vivo are underway but their vast numbers alongside differing enhancer architectures make it difficult to determine their impact on gene activity. By systematically annotating multiple mouse tissues with super- and typical-enhancers, we have explored their relationship with gene function and phenotype.
RESULTS
Though super-enhancers drive high total- and tissue-specific expression of their associated genes, we find that typical-enhancers also contribute heavily to the tissue-specific expression landscape on account of their large numbers in the genome. Unexpectedly, we demonstrate that both enhancer types are preferentially associated with relevant 'tissue-type' phenotypes and exhibit no difference in phenotype effect size or pleiotropy. Modelling regulatory data alongside molecular data, we built a predictive model to infer gene-phenotype associations and use this model to predict potentially novel disease-associated genes.
CONCLUSION
Overall our findings reveal that differing enhancer architectures have a similar impact on mammalian phenotypes whilst harbouring differing cellular and expression effects. Together, our results systematically characterise enhancers with predicted phenotypic traits endorsing the role for both types of enhancers in human disease and disorders
Dietary Management, Clinical Status and Outcome of Patients with Citrin Deficiency in the UK.
No full textBACKGROUND
Little is known about the optimal dietary treatment for citrin deficiency. Our aim is to describe the management of UK citrin deficiency patients.
METHODS
A longitudinal retrospective review was performed. Data were collected from medical records on presenting signs and symptoms, dietary management and clinical outcome.
RESULTS
data were collected on 32 patients from 21 families. 50% were females (16/32). Median age at diagnosis was 4 y (5 days-35 y) with 12 patients diagnosed in the neonatal period with neonatal intrahepatic cholestasis (NICCD), eight later in childhood (FTTDCD) and 12 by family screening based on index cases from five families. No patient had adult-onset type II citrullinemia. The patient age at the time of data collection was a median of 11 y (1-44 y). 91% (29/32) of patients had normal physical and neurological development, 47% (15/32) experienced recurrent unexplained abdominal pain and 9% (3/32) episodes of hypoglycaemia. Siblings had different phenotypes (5 families had > 1 affected patient). Most patients preferred high protein foods, limiting sugar-containing foods. Only 41% (13/32) were prescribed a low CHO, high protein, high fat diet (restriction varied) and two used medium chain triglyceride (MCT) supplements. No patient was prescribed drug therapy. Twenty-five per cent (8/32) of patients were underweight and 41% (13/32) had height <-1 z-scores.
CONCLUSIONS
patients presented with various phenotypes, symptoms and suboptimal growth. Symptoms and biochemical markers improved with age, but height remained low in some. More research is necessary to assess the effectiveness of dietary approaches in improving clinical outcomes and symptoms in citrin deficiency
Impact of Coronavirus Disease 2019 Pandemic on the Incidence and Management of Out-of-Hospital Cardiac Arrest in Patients Presenting With Acute Myocardial Infarction in England.
No full textBackground Studies have reported significant reduction in acute myocardial infarction-related hospitalizations during the coronavirus disease 2019 (COVID-19) pandemic. However, whether these trends are associated with increased incidence of out-of-hospital cardiac arrest (OHCA) in this population is unknown. Methods and Results Acute myocardial infarction hospitalizations with OHCA during the COVID-19 period (February 1-May 14, 2020) from the Myocardial Ischaemia National Audit Project and British Cardiovascular Intervention Society data sets were analyzed. Temporal trends were assessed using Poisson models with equivalent pre-COVID-19 period (February 1-May 14, 2019) as reference. Acute myocardial infarction hospitalizations during COVID-19 period were reduced by >50% (n=20 310 versus n=9325). OHCA was more prevalent during the COVID-19 period compared with the pre-COVID-19 period (5.6% versus 3.6%), with a 56% increase in the incidence of OHCA (incidence rate ratio, 1.56; 95% CI, 1.39-1.74). Patients experiencing OHCA during COVID-19 period were likely to be older, likely to be women, likely to be of Asian ethnicity, and more likely to present with ST-segment-elevation myocardial infarction. The overall rates of invasive coronary angiography (58.4% versus 71.6%; <0.001) were significantly lower among the OHCA group during COVID-19 period with increased time to reperfusion (mean, 2.1 versus 1.1 hours; =0.05) in those with ST-segment-elevation myocardial infarction. The adjusted in-hospital mortality probability increased from 27.7% in February 2020 to 35.8% in May 2020 in the COVID-19 group (<.001). Conclusions In this national cohort of hospitalized patients with acute myocardial infarction, we observed a significant increase in incidence of OHCA during COVID-19 period paralleled with reduced access to guideline-recommended care and increased in-hospital mortality
A Rare Case of Fungal Rhinosinusitis Caused by Scedosporium apiopermum.
No full textFungal rhinosinusitis (FRS) is inflammation of the paranasal sinus mucosa due to fungal infections, which can be invasive or non-invasive. The occurrence of a sphenoid mucocele with a fungal ball is rare. We report a case of sphenoid sinus mucocele with a fungal ball caused by Scedosporium apiopermum in a 32-year-old female who presented to the Emergency Department with persistent headache not relieved on medications. The radiological images showed a mucocele with clival osteomyelitis. Urgent endoscopic examination and debridement was undertaken which demonstrated a mucocele with fungal ball. Microbiological examination confirmed it to be Scedosporium apiopermum
Optical coherence tomography confirms shunt malfunction and recurrence of raised intracranial pressure in optic atrophy.
No full textBACKGROUND
Investigating potential cerebrospinal fluid (CSF) shunt malfunction can be a challenge. Optical coherence tomography (OCT), a non-invasive imaging technique, is used to monitor changes at the optic nerve head in papilloedema. Conventional teaching suggests that in the presence of optic atrophy the optic nerve head may not re-swell in response to a relapse in raised intracranial pressure (ICP).
METHODS
A retrospective case series of three patients who had prior CSF diversion surgery for idiopathic intracranial cranial hypertension (IIH) is presented demonstrating the benefit of non-invasive OCT imaging confirming raised ICP.
RESULTS
Recurrence of raised ICP, due to malfunctioning CSF shunt, was diagnosed in three patients requiring further surgical intervention. All re-presented acutely with headache and visual disturbances. All had a prior diagnosis of optic atrophy. In all patients, OCT peripapillary retinal nerve fibre layer qualitative image analysis and quantified progression analysis permitted easy detection of the recurrence of papilloedema.
CONCLUSION
OCT imaging supports clinical decision making in shunt malfunction, even in the presence of established optic atrophy secondary to IIH
Staff and Users' Experiences of Pharmacy-Based Sexual and Reproductive Health Services: A Qualitative Interview Study from the UK.
No full textSince August 2015, a large range of sexual health and reproductive health services have been provided in more than 120 pharmacies across Birmingham (England). Our study aimed to explore how pharmacy staff and pharmacy users experience delivering or being provided with sexual health and reproductive health services. Between March and September 2019, semi-structured interviews were conducted with 15 pharmacy staff delivering sexual and reproductive health services and 15 people who had used a sexual and reproductive health service at the pharmacy. Interviews were analysed thematically. Pharmacy users found services convenient to use and were largely satisfied with pharmacy staff consultation skills. Staff were motivated to deliver the services, although some felt that they did not receive sufficient recognition for their work. Barriers to pharmacy-based sexual and reproductive health services were identified, including lack of privacy for users, lack of staff and user awareness of the services, lack of trained staff to deliver services and lack of capacity for copper coil insertions in females presenting for emergency contraception. The identification of barriers to effective service provision can be used to improve the delivery of sexual and reproductive health services in pharmacies and lead to a greater uptake
Venous thromboembolism in patients with COVID-19 and correlation with D-dimers: a single-centre experience.
No full textOBJECTIVE
To study the frequency of venous thromboembolism in hospitalised patients with COVID-19 and correlation with the D-dimers and thromboprophylaxis.
DESIGN
Cross-sectional descriptive study.
PLACE AND DURATION OF STUDY
Queen Elizabeth Hospital, 20 April 2020-13 May 2020.
PATIENTS AND METHODS
One hundred and seven (n=107) patients of PCR-confirmed COVID-19 pneumonia admitted to Queen Elizabeth Hospital, Birmingham, between 20 April 2020 and 13 May 2020 were included in the study using consecutive sampling. Data were collected using the Excel audit tool and included age, gender, weight, estimated eGFR, D-dimer values on admission, intensive care unit admission, presence of respiratory failure, imaging results for evaluation of venous thromboembolism (VTE) and anticoagulation received on admission. The data were entered in the SPSS (V.17) and were analysed. Data were summarised as means±SD, number or percentage as appropriate. A p value of less than 0.05 was considered significant.
RESULTS
The frequency of VTE was found to be 11.2% in patients hospitalised with COVID-19 pneumonia. The mean D-dimers were 3322.24 ng/mL±9603 ng/mL with the values significantly higher for patients with VTE and those requiring intensive care unit admission. All of the seven patients (100%) with D-dimers value above 2000 ng/mL who underwent imaging were found to have VTE.
CONCLUSION
VTE is frequent in patients with COVID-19 pneumonia despite anticoagulation. A higher D-dimers value correlates well with the risk of VTE in these patients and further evaluation of such patients for VTE is necessary especially with D-dimers values above 2000 ng/mL
How I do it…. How infection doctors approach the PJI MDT.
No full textThe management of prosthetic joint infection (PJI) requires discussion between experts working towards the aims and expectations of the patient. Each discipline typically does not offer a single-minded approach, but instead collectively weighs up the strengths and weaknesses of different management options. At a basic level, the infection specialist provides antimicrobial solutions based on laboratory results. During multi-disciplinary team (MDT) discussions however, they can offer additional insights into how the microbiology could influence the surgical decisions, respond to the surgical debate by designing a rational approach to antimicrobials and contribute to an option-appraisal that can be presented to the patient. In this short opinion piece, we describe some of the thoughts we have during MDT discussions to ultimately recommend an optimised treatment plan for the individual patient: is there infection? what is the pathogen? where did it come from? (and where else has it gone), and what is the best treatment strategy
Non-steroidal anti-inflammatory drugs and susceptibility to COVID-19.
No full textOBJECTIVES
To identify whether active use of non-steroidal anti-inflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed COVID-19 compared to the use of other common analgesics.
METHODS
We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. The cohort consisted of adult patients aged ≥18 years with a diagnosis of osteoarthritis and followed up from 30 January to 31 July 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). We identified 13,202 patients prescribed NSAIDs compared to 12,457 prescribed the comparator drugs. The primary outcome was documentation of suspected or confirmed COVID-19 and secondary outcome measure was all-cause mortality.
RESULTS
During follow up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1000 person-years in the NSAID-exposed and comparator groups, respectively. Adjusted hazard ratios in the unmatched and propensity score matched analyses for primary care consultations with suspected/confirmed COVID-19 were 0.82 (95% CI 0.62-1.10) and 0.79 (95% CI 0.57-1.11) respectively, and for subsequent mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20). There was no effect modification by age or sex.
CONCLUSION
We did not observe an increased risk of suspected or confirmed COVID-19 or mortality among patients in primary care with osteoarthritis who were prescribed NSAIDs compared to comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic