5366 research outputs found
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Endocrinology in the time of COVID-19: Management of calcium disorders and osteoporosis.
No full textEndocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to online resources e.g. Society for Endocrinology, Royal Osteoporosis Society, International Osteoporosis Foundation, specific patient groups and the European Reference Networks (ERNs) for Rare Endocrine and Rare Bone disorders. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. A pragmatic, symptom-based approach should be implemented in patients at the end of life. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6-9 months during the pandemic. Patients established on denosumab and teriparatide should continue planned therapy. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath
Testosterone replacement therapy: Pre-treatment sex hormone binding globulin levels and age may identify clinical subgroups.
No full textBACKGROUND
Testosterone replacement therapy (TRT) improves health in some but not all men with type 2 diabetes (T2DM) and adult onset testosterone deficiency (TD). Such heterogeneity is compatible with the concept of patient subgroups that respond differently to therapy.
OBJECTIVES
Use baseline SHBG and age to identify putative subgroups that demonstrate different responses in variables such as waist circumference and HbA1c following TRT.
MATERIALS AND METHODS
A randomised double-blind trial approach was used to recruit and randomise men with T2DM and adult onset TD into placebo and TRT treated groups. Multiple regression was used to study differences between groups.
RESULTS
Baseline SHBG and change in SHBG (∆SHBG) were inversely related in the TRT group. Both median values of SHBG and age mediated the effect of TRT on ∆SHBG depending on whether baseline values were ≤ or >median (28.1nmol/l, 63 years respectively). In men with both SHBG≤28.1 nmol/l and age≤63 years (subgroup 1), TRT was positively associated with ∆SHBG (c = 4.67, 95%CI 1.17 - 8.16, p=0.010) while in those with SHBG>28.1 nmol/l and age>63.1 years (subgroup 4) the association was inverse (c = -7.07, 95%CI -11.64 - -2.49, p=0.003). The association between TRT and change (∆) in waist circumference, HbA1c and International Index of Erectile Function (IIEF) score differed between subgroups; in subgroup 4 but not subgroup 1, the therapy was significantly, associated with ∆waist circumference, ∆HbA1c and ∆IIEF.
DISCUSSION
Though the mechanism remains unclear, our finding of different responses to TRT in terms of change in waist circumference, HbA1c and IIEF score supports the concept of subgroups in men with T2DM and adult onset TD.
CONCLUSION
Our approach may provide a basis for identifying men who will or will not derive benefit from TRT though a larger study is required
Development and in vivo evaluation of Irinotecan-loaded Drug Eluting Seeds (iDES) for the localised treatment of recurrent glioblastoma multiforme.
No full textGlioblastoma multiforme (GBM) is impossible to fully remove surgically and almost always recurs at the borders of the resection cavity, while systemic delivery of therapeutic drug levels to the brain tumour is limited by the blood-brain barrier. This research describes the development of a novel formulation of Irinotecan-loaded Drug Eluting Seeds (iDES) for insertion into the margin of the GBM resection cavity to provide a sustained high local dose with reduced systemic toxicities. We used primary GBM cells from both the tumour core and Brain Around the Tumour tissue from recurrent GBM patients to demonstrate that irinotecan is more effective than temozolomide. Irinotecan had a 75% response rate, while only 50% responded to temozolomide. With temozolomide the cell viability was never below 80% whereas irinotecan achieved cell viabilities of less than 44%. The iDES were manufactured using a hot melt extrusion process with accurate irinotecan drug loadings and the same cytotoxicity as unformulated irinotecan. The iDES released irinotecan in a sustained fashion for up to 7 days. However, only the 30, 40 and 50% w/w loaded iDES formulations released the 300 to 1000 μg of irinotecan needed to be effective in vivo. The 30 and 40% w/w iDES formulations containing 10% plasticizer and either 60 or 50% PLGA prolonged survival from 27 to 70 days in a GBM xenograft mouse resection model with no sign of tumour recurrence. The 30% w/w iDES formulations showed equivalent toxicity to a placebo in non-tumour bearing mice. This innovative drug delivery approach could transform the treatment of recurrent GBM patients by improving survival and reducing toxicity
Photopsia.
No full text'Photopsia' describes the symptom of visual disturbances that are typically flash-like, sudden in onset and brief, and occurring without light entering the eye. Patients reporting photopsia often pose a diagnostic challenge, given the wide range of possible neurological and ophthalmological causes. We review the common causes of photopsia, discuss the assessment and workup of this symptom, and stress the importance of close interdisciplinary liaison to help with its diagnosis and management. We discuss a patient with acute zonal occult outer retinopathy to illustrate these points
How, why, for whom and in what context, do sexual health clinics provide an environment for safe and supported disclosure of sexual violence: protocol for a realist review.
No full textINTRODUCTION
Supporting people subjected to sexual violence includes provision of sexual and reproductive healthcare. There is a need to ensure an environment for safe and supported disclosure of sexual violence in these clinical settings. The purpose of this research is to gain a deeper understanding of how, why, for whom and in what circumstances safe and supported disclosure occurs in sexual health services.
METHODS AND ANALYSIS
To understand how safe and supported disclosure of sexual violence works within sexual health services a realist review will be undertaken with the following steps: (1) Focussing of the review including a scoping literature search and guidance from an advisory group. (2) Developing the initial programme theories and a search strategy using context-mechanism-outcome (CMO) configurations. (3) Selection, data extraction and appraisal based on relevance and rigour. (4) Data analysis and synthesis to further develop and refine programme theory, CMO configurations with consideration of middle-range and substantive theories.
DATA ANALYSIS
A realist logic of analysis will be used to align data from each phase of the review, with CMO configurations being developed. Programme theories will be sought from the review that can be further tested in the field.
ETHICS AND DISSEMINATION
This study has been approved by the ethics committee at University of Birmingham, and has Health Research Authority approval. Findings will be disseminated through knowledge exchange with stakeholders, publications in peer-reviewed journals, conference presentations and formal and informal reports. In addition, as part of a doctoral study, the findings will be tested in multisite case studies.
PROSPERO REGISTRATION DETAILS
CRD4201912998. Dates of the planned realist review, from protocol design to completion, January 2019 to July 2020
Endoscopic resection of colon dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis.
No full textBACKGROUND AND AIMS
Inflammatory bowel disease (IBD) is a well-known risk factor for colorectal cancer (CRC). Current guidelines propose complete endoscopic resection of dysplasia in IBD patients with close endoscopic follow-up. Current data on the risk of neoplasia after endoscopic resection of dysplasia in IBD patients are limited.
METHODS
Multiple databases were searched from inception through August 2019 to identify studies that reported on incidence and/or recurrence of neoplasia after resection of dysplasia in patients with IBD. Outcomes from the included studies were pooled to estimate the risk of neoplasia after dysplasia resection in IBD patients.
RESULTS
From a total of 18 studies, 1037 IBD patients underwent endoscopic resection for a total of 1428 colonic lesions. After lesion resection, the pooled risk (in rate per 1000 person years of follow-up) of CRC was 2 (95% confidence interval [CI], 0-3), the pooled risk of HGD was 2 (95% CI, 1-3) and the pooled risk of any lesion was 43 (95% CI, 30-57). Meta-regression analysis based on lesion location (right, left), lesion size (mean and/or median size in mm), lesion type (Paris-I, Paris-II), endoscopic resection technique (endoscopic mucosal resection, endoscopic submucosal dissection, or polypectomy), and lesion histology (low-grade dysplasia, high-grade dysplasia) did not influence the reported outcomes.
CONCLUSION
Risk of CRC after dysplasia resection in IBD patients appears to be low, supporting the current strategy of resection and surveillance
Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: a systematic review and meta-analysis.
No full textBACKGROUND
Whole blood (WB) is optimal for resuscitation of traumatic haemorrhage. Walking Blood Banks (WBB) provide fresh whole blood (FWB) where conventional blood components or stored, tested WB are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the COVID-19 pandemic. We conducted a systematic review and meta-analysis of the available evidence to inform practice.
METHODS
Standard systematic review methodology was used to obtain studies that reported the delivery of FWB (PROSPERO registry CRD42019153849). Studies that only reported WB from conventional blood banking were excluded. For outcomes, odds ratios (OR) and 95% confidence interval (CI) were calculated using random effects modelling due to high risk of heterogeneity. Quality of evidence was assessed using the GRADE system.
RESULTS
27 studies published from 2006 - 2020 reported >10,000 units of FWB for >3000 patients (precise values not available for all studies). Evidence for studies was "low" or "very low" except for one study which was "moderate" in quality. FWB patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for 8 studies that compared these (OR 1.00 (95% CI 0.65, 1.55); p=0.61). However, the highest quality study (matched groups for physiological and injury characteristics) reported an adjusted OR of 0.27 (95% CI 0.13-0.58) for mortality for the FWB group; p<0.01.
CONCLUSIONS
Thousands of units of FWB from WBBs have been transfused in patients following life-threatening haemorrhage. Survival is equivalent for FWB resuscitation when compared to non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas WBB may be an attractive resilience measure, caution is still advised. WBBs should be subject to prospective evaluation to optimise care and inform policy.
LEVEL OF EVIDENCE
Therapeutic, level 3
Successful penile replantation after complete amputation and 23 hours ischaemia time: the first in reported literature.
No full textComplete penile amputation is a rare and poorly documented injury with severe physical and psychosocial implications. Our institution presents a case of successful penile replantation following 23 hours of ischaemia time in a 34-year-old man with a history of paranoid schizophrenia who sustained a complete penile amputation during an act of deliberate self-harm. To the best of our knowledge, this is the longest documented ischaemia time for a successful penile replant in literature. The patient was able to achieve a full erection as early as 6 weeks postoperatively. Skin necrosis was noted as a common complication and this was successfully managed with debridement and skin grafting. Penile amputation injuries should be managed in a specialist centre with urological and plastic surgeons with expertise in microsurgical reconstruction. Penile replantation should be attempted, even if ischaemia time is prolonged, despite lower success rates given the significance of the injury to an individual