Subject(s)
COVID-19 , Dermatology , Humans , COVID-19/epidemiology , Pandemics , Ambulatory Care , PerceptionABSTRACT
Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8-27.1% of patients experiencing a rash of any grade, and 5.2-6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky's sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.
Subject(s)
Plastic Surgery Procedures , Skin Transplantation , Humans , Lip/surgery , Metaplasia/surgery , Surgical FlapsABSTRACT
Dual epidermal neoplasms are rare. There are several different types, including a combined tumour, which is highlighted in this case. Several theories exist to the origin of these tumours. They are best appreciated with immunohistochemistry staining. Treatment is by excision.
Subject(s)
Neoplasms , Humans , ImmunohistochemistryABSTRACT
BACKGROUND: Panniculitis represents a rare and potentially lethal manifestation of alpha-1 antitrypsin deficiency (AATD). Evidence regarding management is limited to case reports and small case series. We sought to clarify typical features and investigation of AATD-associated panniculitis and assess the evidence regarding therapeutic options. SEARCH METHODOLOGY: Articles and abstracts published between 1970 and 2020 were identified by searches of MEDLINE, PubMed, and secondary searches of references from relevant articles using the search terms "panniculitis," "alpha-1," "antitrypsin," "deficiency," and "Weber-Christian." FINDINGS: We identified 117 cases of AATD-associated panniculitis. In 1 series, AATD was present in 15% of all cases of biopsy-proven panniculitis. Failure to achieve clinical response was seen in all instances of systemic steroid use. Dapsone, although effective and accessible, is frequently associated with failure to achieve remission. In these instances, intravenous AAT augmentation therapy generally resulted in response. CONCLUSIONS: AATD may be more prevalent among patients presenting with panniculitis than previously thought. Patients presenting with panniculitis and systemic illness show high mortality risk. Although most cases are associated with the severe ZZ-genotype, moderate genotypes may also predispose to panniculitis. Dapsone remains the most cost-effective therapeutic option, whereas intravenous AAT augmentation remains the most efficacious. Finally, glucocorticoids appear ineffective in this setting.
Subject(s)
Panniculitis , alpha 1-Antitrypsin Deficiency , Dapsone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Panniculitis/complications , Panniculitis/etiology , alpha 1-Antitrypsin/genetics , alpha 1-Antitrypsin/therapeutic use , alpha 1-Antitrypsin Deficiency/complications , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/drug therapyABSTRACT
The deployment of a UK military Role 2 Medical Treatment Facility (MTF) to South Sudan during Operation TRENTON into an isolated location and austere environment with a prolonged hold produced potential medical planning challenges. The MTF was augmented with both specific personnel and equipment in order to meet these challenges. This paper discusses equipment available in this facility not previously used at Role 2 before and how it could be used to supplement medical operational deployments in future.
Subject(s)
Military Medicine , Military Personnel , Health Facilities , Humans , South Sudan , United KingdomABSTRACT
OBJECTIVES: With ever increasingly complex healthcare settings, technology enhanced simulation (TES) is well positioned to explore all perspectives to enhance patient safety and patient outcomes. Analysis from a Safety-II stance requires identification of human adjustments in daily work that are key to maintaining safety. The aim of this paper is to describe an approach to explore the consequences of human variability from a Safety-II perspective and describe the added value of this to TES. METHODS: The reader is guided through a novel application of functional resonance analysis methodology (FRAM), a method to analyse how a system or activity is affected by human variability, to explore human adaptations observed in in situ simulations (ISS). The structured applicability of this novel approach to TES is described by application to empirical data from the standardised ISS management of paediatric time critical head injuries (TCHI). RESULTS: A case series is presented to illustrate the step-wise observation of key timings during ISSs, the construction of FRAM models and the visualisation of the propagation of human adaptations through the FRAM models. The key functions/actions that ensure the propagation are visible, as are the sequelae of the adaptations. CONCLUSIONS: The approach as described in this paper is a first step to illuminating how to explore, analyse and observe the consequences of positive and negative human adaptations within simulated complex systems. This provides TES with a structured methodology to visualise and reflect upon both Safety-I and Safety-II perspectives to enhance patient safety and patient outcomes.
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BACKGROUND: Adult and paediatric basic life support (BLS) training are often conducted via group training with an accredited instructor every 24 months. Multiple studies have demonstrated a decline in the quality of cardio-pulmonary resuscitation (CPR) performed as soon as 3-month post-training. The 'Resuscitation Quality Improvement' (RQI) programme is a quarterly low-dose, high-frequency training, based around the use of manikins connected to a cart providing real-time and summative feedback. We aimed to evaluate the effects of the RQI Programme on CPR psychomotor skills in UK hospitals that had adopted this as a method of BLS training, and establish whether this program leads to increased compliance in CPR training. METHODS: The study took place across three adopter sites and one control site. Participants completed a baseline assessment without live feedback. Following this, participants at the adopter sites followed the RQI curriculum for adult CPR, or adult and infant CPR. The curriculum was split into quarterly training blocks, and live feedback was given on technique during the training session via the RQI cart. After following the curriculum for 12/24 months, participants completed a second assessment without live feedback. RESULTS: At the adopter sites, there was a significant improvement in the overall score between baseline and assessment for infant ventilations (N = 167, p < 0.001), adult ventilations (n = 129, p < 0.001), infant compressions (n = 163, p < 0.001) adult compressions (n = 205, p < 0.001), and adult CPR (n = 249, p < 0.001). There was no significant improvement in the overall score for infant CPR (n = 206, p = 0.08). Data from the control site demonstrated a statistically significant improvement in mean score for adult CPR (n = 22, p = 0.02), but not for adult compressions (N = 18, p = 0.39) or ventilations (n = 17, p = 0.08). No statistically significant difference in improvement of mean scores was found between the grouped adopter sites and the control site. The effect of the duration of the RQI curriculum on CPR performance appeared to be minimal in this data set. Compliance with the RQI curriculum varied by site, one site maintained hospital compliance at 90% over a 1 year period, however compliance reduced over time at all sites. CONCLUSIONS: This data demonstrated an increased adherence with guidelines for high-quality CPR post-training with the RQI cart, for all adult and most infant measures, but not infant CPR. However, the relationship between a formalised quarterly RQI curriculum and improvements in resuscitation skills is not clear. It is also unclear whether the RQI approach is superior to the current classroom-based BLS training for CPR skill acquisition in the UK. Further research is required to establish how to optimally implement the RQI system in the UK and how to optimally improve hospital wide compliance with CPR training to improve the outcomes of in-hospital cardiac arrests.
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The objective of this study was to determine whether a single session of exercise was sufficient to induce cerebral adaptations in individuals with Huntington's disease and to explore the time dynamics of any acute cerebrovascular response. In this case-control study, we employed arterial-spin labelling MRI in 19 Huntington's disease gene-positive participants (32-65 years, 13 males) and 19 controls (29-63 years, 10 males) matched for age, gender, body mass index and self-reported activity levels, to measure global and regional perfusion in response to 20 min of moderate-intensity cycling. Cerebral perfusion was measured at baseline and 15, 40 and 60 min after exercise cessation. Relative to baseline, we found that cerebral perfusion increased in patients with Huntington's disease yet was unchanged in control participants in the precentral gyrus (P = 0.016), middle frontal gyrus (P = 0.046) and hippocampus (P = 0.048) 40 min after exercise cessation (+15 to +32.5% change in Huntington's disease participants, -7.7 to 0.8% change in controls). The length of the disease-causing trinucleotide repeat expansion in the huntingtin gene predicted the change in the precentral gyrus (P = 0.03) and the intensity of the exercise intervention predicted hippocampal perfusion change in Huntington's disease participants (P < 0.001). In both groups, exercise increased hippocampal blood flow 60 min after exercise cessation (P = 0.039). These findings demonstrate the utility of acute exercise as a clinically sensitive experimental paradigm to modulate the cerebrovasculature. Twenty minutes of aerobic exercise induced transient cerebrovascular adaptations in the hippocampus and cortex selectively in Huntington's disease participants and likely represents latent neuropathology not evident at rest.
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The surge of coronavirus disease 2019 (COVID-19) research studies involving human participants in response to the pandemic has meant that research ethics committees across the world have been challenged to adapt their processes to meet demand while retaining high standards of review. Ethics review during this pandemic remains essential to ensure the safety, dignity and well-being of research participants, however research ethics committees are now faced with new, and often complex, ethics considerations and logistical challenges. This Open Letter looks specifically at the Irish experience of establishing a national approach to research ethics review amidst a global pandemic. This represents Ireland's first National Research Ethics Committee, which provided the research community with an expedited and 'single national opinion' for ethics review for COVID-related research. The insights gleaned and lessons learned from the Irish experience may inform emergency responses to future pandemics or public health emergencies.
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OBJECTIVES: Trauma is the leading cause of death in children. The lack of an accepted definition of what constitutes a high-quality stabilisation of a traumatically injured child has limited the evaluation of direct interventions in simulation-based education and service-delivery models to improve trauma care. The aim of this study was to create a framework that delineates quality by exploring the perceptions of the multi-disciplinary team providing and improving this initial care. METHODS: Interviews were conducted with 36 experienced UK trauma team members and governance administrators (clinical directors to executive board level), from three standard UK trauma units. This study used a phenomenographic approach to explore the relationships and hierarchy between the contrasting perceptions of quality and evaluation of quality in this acute context. RESULTS: The findings show that defining quality is a more complex concept than simple proxy measurements, such as time to CT scanning. They also show that the concept of quality requires the consideration of a spectrum of perspectives that range from the simple to the more sophisticated.This study highlights the importance of teamwork, individualised perspectives and the culture of care provision, when describing quality. A novel framework to delineate quality is presented, comprising System, Team, Process, Individual, Data and Culture. CONCLUSIONS: This study has created a framework of understanding of acute paediatric trauma care quality and its measurement from the perspectives of team members and administrators. A framework and future tools to capture and disseminate the System, Team, Process, Individual, Data and Culture perspectives of the quality of trauma stabilisations could be a key advance in the care of severely injured children.
ABSTRACT
INTRODUCTION: As part of a programme of research aiming to improve the outcomes of traumatically injured children, a multisource healthcare advocacy tool has been developed to allow trauma team members and hospital governance administrators to reflect and to act on complex trauma team-hospital systems interactions. We have termed this tool a Field Assessment Conditioning Tool (FACT). The FACT draws on quantitative data including clinical care points in addition to self-reflective qualitative data. The FACT is designed to provide feedback on this assessment data both horizontally across fellow potential team members and vertically to the hospital/organisation governance structure, enabling process gap identification and allowing an agenda of improvements to be realised. The aim of the study described in this paper is to explore the perceived fitness for purpose of the FACT to provide an opportunity for healthcare advocacy by healthcare professionals caring for traumatically injured children. METHODS AND ANALYSIS: The FACT will be implemented and studied in three district hospitals, each around a major trauma centre in the UK, USA and New Zealand. Using a qualitative approach with standardised semi-structured interviews and thematic analysis we will explore the following question: Is the FACT fit for purpose in terms of providing a framework to evaluate, reflect and act on the individual hospital's own performance (trauma team-hospital interactions) in terms of readiness to receive traumatically injured children? ETHICS AND DISSEMINATION: Ethics opinion was sought for each research host organisation participating and deemed not required. The results will be disseminated to participating sites, networks and published in high-impact journals.
Subject(s)
Health Services Research/methods , Multiple Trauma/therapy , Outcome and Process Assessment, Health Care/methods , Quality Assurance, Health Care/standards , Child , Humans , Trauma Centers , United KingdomABSTRACT
A series of cysteine-stabilized phenolic resin-based polymer and carbon spheres were prepared by the modified Stöber method. Cysteine plays a very important role in the proposed one-pot synthesis of the aforementioned spheres; namely, it acts as a particle stabilizer and a source of heteroatoms (nitrogen and sulfur) that can be introduced into these spheres. The diameter of these spheres can be tuned in the range of 70-610 nm by adjusting the cysteine amount and reaction temperature. Since polymer spheres obtained in the presence of cysteine contain sulfur and nitrogen heteroatoms, they were tested for adsorption of copper ions. It is shown that adsorption isotherms recorded for copper ions can be well fitted by Langmuir equation, giving unprecedented adsorption capacities up to ~65 mg/g.
Subject(s)
Carbon/chemistry , Copper Sulfate/isolation & purification , Cysteine/chemistry , Formaldehyde/chemistry , Phenols/chemistry , Polymers/chemistry , Adsorption , Nitrogen/chemistry , Particle Size , Sulfur/chemistry , Temperature , Water Purification/methodsABSTRACT
The principles of evidence-based medicine (EBM) applied to pediatric anesthesia could result in a potent educational tool. At present there is a limited structured evidence base to pediatric anesthesia. However, the wide array of pediatric anesthetic research and clinical practice itself are well suited to the principles of EBM. Best evidence topics could be considered the starting point for a potentially extremely useful evidence-based pediatric anesthesia database.
Subject(s)
Anesthesia/standards , Decision Support Techniques , Evidence-Based Medicine/methods , Randomized Controlled Trials as Topic/standards , Research DesignABSTRACT
Evidence based medicine (EBM) is a potent patient centered clinical learning strategy. EBM facilitates efficient robust decision making on an individual patient basis. It provides the framework and tools to rapidly and effectively find answers to specific clinical questions and educate others. At the core of EBM is clinical judgement. This is the ability to combine clinical experience and expertise with the best available evidence in the literature to answer a specific pediatric anesthesia question.
Subject(s)
Anesthesia , Decision Making , Evidence-Based Medicine/methods , Pediatrics , Bias , Clinical Protocols/standards , Data Interpretation, Statistical , Humans , Metabolic Clearance Rate , Research DesignABSTRACT
Coughing on emergence can result in a number of undesirable side effects, including hypertension, tachycardia, tachyarrhythmias, increased intracranial pressure, and increased intraocular pressure. The efficacy of endotracheal spraying with lidocaine at the time of intubation in preventing coughing on emergence is unknown. In a double-blind placebo-controlled study, we randomized 50 ASA physical status I and II patients presenting for elective gynecological surgery <2 h duration to receive either endotracheal lidocaine 160 mg or placebo before intubation. Both groups were comparable in terms of demographics and intraoperative conditions. The incidence of coughing before tracheal extubation was less frequent in the lidocaine group (26%) than in the placebo group (66%, P < 0.01), as was the incidence after tracheal extubation (4% versus 30%, P = 0.022). This study supports the use of endotracheal lidocaine before intubation in patients undergoing general anesthesia for surgery <2 h duration where coughing on emergence is undesirable.