5366 research outputs found
Sort by
Congenital adrenal hyperplasia - current insights in pathophysiology, diagnostics and management.
No full textCongenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21- hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000 there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in congenital adrenal hyperplasia with special attention to these new developments
Intracranial haemorrhage in immune thrombotic thrombocytopenic purpura treated with caplacizumab.
No full textImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening condition resulting from IgG autoantibodies to 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13). Severe ADAMTS13 deficiency causes accumulation of ultra-large von Willebrand factor (VWF) multimers which bind platelets, leading to widespread microvascular thrombosis, compromise of critical organs and profound thrombocytopenia . In the absence of treatment, TTP is usually fatal
Reply to Trey Durdin, Alvin Goh, and Eugene Pietzak. Can an Imaging-guided Pathway Replace the Current Paradigm for Muscle-invasive Bladder Cancer? Eur Urol. In press. https://doi.org/10.1016/j.eururo.2021.03.018.
No full textThe Volunteers in Research programme: supporting COVID-19 research and improving medical training in parallel.
No full textCOVID-19 has had an unprecedented impact on society, global healthcare and daily life. The redeployment of research staff to patient-facing roles in the NHS left a depleted workforce to deliver critical urgent public health research (UPHR). We aimed to support UPHR studies and medical student training by developing and implementing a medical student Volunteers in Research programme. We further sought to gain insights about medical students' perceptions of this programme. We collected prospective data and conducted a retrospective survey as part of a service evaluation to assess the value of this clinical research experience to students, as well as motivators and barriers to taking part. The Volunteers in Research programme successfully supported UPHR studies during the COVID-19 pandemic. We generated important insights to help aid the wider implementation of this programme nationally to support essential research and medical student education
Systematic review of the stability of antimicrobial agents in elastomeric devices for outpatient parenteral antimicrobial therapy services based on NHS Yellow Cover Document standards.
No full textBACKGROUND
In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial agents to assign a product shelf-life. In the UK, the relevant standards for stability testing and shelf-life assignment are published in 'A Standard Protocol for Deriving and Assessment of Stability-Part 1 (Aseptic Preparations-Small Molecules), commonly called the Yellow Covered Document (YCD). A previous systematic review published in 2017 failed to identify data on the stability of antimicrobials in elastomeric devices for OPAT services that met YCD requirements in force at the time. The aim of this review was to update that search, following a subsequent change to YCD requirements in 2017 and 2019 and expand that dataset to identify progress made in providing assurance about the stability of antimicrobial agents for OPAT services.
METHODS
Searches were undertaken for papers relating to extended stability of antimicrobials. Citations were included when antimicrobial shelf-life was assessed using a stability-indicating method and considered a period of storage, either refrigerated or at room temperature, followed by in-use testing at a temperature at or above 32°C.
RESULTS
Of 267 initial citations, six met the inclusion criteria and underwent full text review for data extraction. Included antimicrobials were cefazolin, ceftazidime, piperacillin/tazobactam, flucloxacillin and ceftolozane/tazobactam. Of these, only flucloxacillin and piperacillin demonstrated YCD compliant stability over the 24-hour infusion period while cefazolin, ceftazidime and ceftolozane/tazobactam could be infused over 12-hour period.
CONCLUSIONS
Contrary to the position found in 2017 review, high-quality data are now available to support the use of a number of antimicrobial agents in extended infusion in elastomeric devices for OPAT services. There is a need to expand the dataset, as well as developing international consensus on the ideal parameters for stability assessment of such infusions in elastomeric devices
Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.
No full textOBJECTIVE
Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE.
STUDY DESIGN
COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition.
SETTING
Stakeholders from the United Kingdom.
SUBJECTS AND METHODS
Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition.
RESULTS
Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'.
CONCLUSION
The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life
Home phototherapy for neonatal jaundice in the UK: a single-centre retrospective service evaluation and parental survey.
No full textBackground
In the UK setting, where neonatal jaundice treatment is required, it is largely carried out in hospitals. However, it is possible to safely administer home phototherapy (HPT).
Objective
To report on our centre's experience of HPT and its potential benefits.
Design
Retrospective observational study performed as a service evaluation.
Patients
Infants ≥35 weeks corrected gestational age with a weight of 2 kg and serum bilirubin ≤50 µmol/L above treatment thresholds. Controls were a matched group of infants who received inpatient phototherapy (IPT).
Setting
The catchment area of two neonatal intensive care units, one special care unit and a birth centre at four different hospitals that is covered by a single neonatal community outreach nursing team in Birmingham, UK.
Intervention
HPT was started either in the community or as a continuation of IPT. Controls received IPT.
Main outcome measures
The rate of bilirubin reduction, hospital readmission rates and parental satisfaction.
Results
100 infants received HPT while 50 received IPT. No infant showed a progressive rise of serum bilirubin level while receiving HPT. The rate of bilirubin reduction was similar in both HPT and IPT groups (2.4±1.9 and 2.5±1.6 µmol/L/hour, respectively, MD=-0.1, 95% CI -0.74 to 0.53, p=0.74). Readmission rate was 3% in the HPT group. 97% of parents stated that the overall experience was good and 98% would choose HPT if they had their time all over again.
Conclusion
Our programme suggests that HPT for neonatal jaundice can be carried out in a select group of infants. It helps in providing holistic family-centred care and is viewed positively by families
Evaluating clinician compliance of the clinical frailty score tool for patients admitted with suspected or confirmed COVID-19: a quality improvement project.
No full textDoes powered stapler improve the mechanical integrity of gastrojejunal anastomosis compared to the current techniques? Experimental study in porcine models.
No full textBackground
Numerous techniques have been described for fashioning gastrojejunostomy (GJ) in a Roux-en-Y gastric bypass. These include hand-sewn anastomosis (HSA) and mechanical anastomosis; the latter includes circular stapled anastomosis (CSA) or manual linear stapled anastomosis (mLSA). More recently, this list also includes powered linear stapled anastomosis (pLSA). The aim of this study was to analyse if addition of power to stapling would improve the integrity of GJ anastomosis in ex vivo porcine models.
Subjects and Methods
The present study included five groups - mLSA1, mLSA2, HSA, CSA, and pLSA. Sequential infusions of methylene blue-coloured saline were performed into the GJ models. Pressure readings were recorded till the point of leak denoting burst pressure (BP). Total volume (TV) and site of leak were recorded. Compliance was calculated from the equation ΔTV/ΔBP.
Results
Differences in pouch and intestinal thickness were not statistically significant between the models. BPs were higher in the mechanical anastomosis groups, i.e., pLSA 21 ± 9.85 mmHg, CSA 20.33 ± 5.78 mmHg, mLSA1 18 ± 4.69 mmHg and mLSA2 11 ± 2.94 mmHg, when compared to HSA 9.67 ± 3.79 mm Hg, which was found to be statistically significant (Kruskal-Wallis test, P = 0.03). Overall, the highest BP was recorded for powered stapling followed by circular, and then, linear stapling; however, this difference was not statistically significant (P = 0.86). There was no statistically significant difference among groups with regard to compliance (Kruskal-Wallis test, P = 0.082).
Conclusion
Despite the limited number of samples, mechanical anastomosis showed a statistically higher BP when compared to HSA, suggesting better anastomotic integrity. The pLSA group showed promising results with the highest BP recorded among all groups; however, this did not reach statistical significance
The Effectiveness and Safety of Intrathecal Fluorescein in the Management of Cerebrospinal Fluid Leaks.
No full textBACKGROUND
Cerebrospinal fluid (CSF) leaks can be associated with significant morbidity such as meningitis. Surgical management has proven effective, with endoscopic approaches having become the gold standard due to success rates >90%. Inability to localise the leak site prior to surgery is associated with surgical failure. The use of intrathecal fluorescein (IF) to localise CSF fistulae sites was first demonstrated in 1960. Despite this, its use in this context is unlicensed.
OBJECTIVE
Evaluate the safety and efficacy of IF use in the management of CSF leak repairs in our centre.
METHODS
All patients who underwent endoscopic repair of CSF fistula by a single surgeon where IF was used between January 2010 - September 2019 at a single-centre (tertiary skull base referral unit in the United Kingdom) were retrospectively analysed. Primary outcome measures were localisation of CSF fistula with IF (efficacy) and peri-operative complications likely to be attributable to IF (safety).
RESULTS
There were 55 patients included (60 procedures) with a positive localisation rate of 90.0% with IF. The overall peri-operative complication rate was 8.3% (n = 5). It is likely that none were related to IF use. However, three complications may be linked giving a complication rate potentially related to IF of 5.0%. There were no peri-operative mortalities.
CONCLUSION
Many studies have demonstrated IF to be safe at low doses (<50mg) with a high sensitivity, specificity and positive predicative value. Our results demonstrate that the use of IF in our centre is safe and effective at identifying CSF fistulae. While we have reported some complications in our cohort, these were unlikely to be directly attributable IF use. We have described no serious complications such as seizures, limb weakness or death. We believe this study adds to the growing body of evidence that IF use in the management CSF fistula repairs is safe and effective