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Purpose of Review: Over recent decades, the number of outbreaks caused by fungi has increased for humans, plants (including important crop species) and animals. Yet this problem is compounded by emerging antifungal drug resistance in pathogenic species. Resistance develops over time when fungi are exposed to drugs either in the patient or in the environment. Recent Findings: Novel resistant variants of fungal pathogens that were previously susceptible are evolving (such as Aspergillus fumigatus) as well as newly emerging fungal species that are displaying antifungal resistance profiles (e.g. Candida auris and Trichophyton indotineae). Summary: This review highlights the important topic of emerging antifungal resistance in fungal pathogens and how it evolved, as well as how this relates to a growing public health burden.
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Introduction: Point-of-care ultrasound (POCUS) has an established role in the management of the critically ill. Information and experience of its use in those with COVID-19 disease is still evolving. We undertook a review of cardiac and thoracic ultrasound examinations in patients with COVID-19 on the intensive care unit (ICU). Our aim was to report key findings and their impact on patient management. Methods: A retrospective evaluation of critically ill patients with COVID-19 was undertaken in three adult ICUs, who received point-of-care cardiac and/or thoracic ultrasound during the 2019-2020 COVID-19 pandemic. We recorded baseline demographic data, principal findings, change in clinical management and outcome data. Results: A total of 55 transthoracic echocardiographic examinations scans were performed on 35 patients. 35/55 (64%) echocardiograms identified an abnormality, most commonly a dilated or impaired right ventricle (RV) and 39/55 (70%) scans resulted in a change in management. Nine patients (26%) were found to have pulmonary arterial thrombosis on CTPA or post-mortem. More than 50% of these patients showed evidence of right ventricular dilatation or impairment. Of the patients who were known to have pulmonary arterial thrombosis and died, 83% had evidence of right ventricular dilatation or impairment. 32 thoracic ultrasound scans were performed on 23 patients. Lung sliding and pleural thickening were present bilaterally in all studies. Multiple B-lines were present in all studies, and sub-pleural consolidation was present bilaterally in 72%. Conclusion: POCUS is able to provide useful and clinically relevant information in those critically ill with COVID-19 infection, resulting in change in management in a high proportion of patients. Common findings in this group are RV dysfunction, multiple B-lines and sub-pleural consolidation.
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BACKGROUND: Training a skilled healthcare workforce is an essential part in reaching the United Nations Sustainable Development Goal to end preventable deaths in children and neonates. The greatest burden of mortality lies in low and lower-middle income countries (LLMIC). Short term, in-service courses have been implemented in many LLMIC to improve the quality of care delivered, but the evaluation methods of these courses are inconsistent. METHOD: Studies describing evaluations of course and outcome measures were included if the course lasted seven days or less with postgraduate participants, included paediatric or neonatal acute or emergency training and was based in a LLMIC. This narrative review provides a detailed description of evaluation methods of course content, delivery and outcome measures based on 'Context, Input, Process and Product' (CIPP) and Kirkpatrick models. RESULTS: 5265 titles were screened with 93 articles included after full-text review and quality assessment. Evaluation methods are described: context, input, process, participant satisfaction, change in learning, behaviour, health system infrastructure and patient outcomes. CONCLUSIONS: Outcomes, including mortality and morbidity, are rightly considered the fundamental aim of acute-care courses in LLMIC. Course evaluation can be difficult, especially with low resources, but this review outlines what can be done to guide future course organisers in providing well-conducted courses with consistent outcome measures for maximum sustainable impact.
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Países en Desarrollo , Personal de Salud , Recién Nacido , Niño , Humanos , Personal de Salud/educación , Aprendizaje , Curriculum , Evaluación de Resultado en la Atención de SaludRESUMEN
Hyperammonaemia is a life-threatening condition with numerous aetiologies and a variable presentation. It is increasingly associated with bariatric weight-loss procedures and significant mortality despite treatment. Symptoms often occur long after surgery and at times in association with other trigger illnesses. Patients can present to general medicine, general practice and intensive care as well as surgical and anaesthetic teams. We present the case of a male patient who underwent a sleeve gastrectomy with subsequent weight loss and suffered from hyperammonaemic encephalopathy on multiple occasions. His delayed postoperative complication was likely to be multifactorial in nature, and this is outlined in the case. We discuss presentation, investigation, management and patient outcomes.
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Cirugía Bariátrica , Encefalopatías , Síndromes de Neurotoxicidad , Obesidad Mórbida , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Encefalopatías/etiología , Encefalopatías/cirugía , Gastrectomía/efectos adversos , Gastrectomía/métodos , Humanos , Masculino , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Candida glabrata is the second most common etiological cause of worldwide systemic candidiasis in adult patients. Genome analysis of 68 isolates from 8 hospitals across Scotland, together with 83 global isolates, revealed insights into the population genetics and evolution of C. glabrata. Clinical isolates of C. glabrata from across Scotland are highly genetically diverse, including at least 19 separate sequence types that have been recovered previously in globally diverse locations, and 1 newly discovered sequence type. Several sequence types had evidence for ancestral recombination, suggesting transmission between distinct geographical regions has coincided with genetic exchange arising in new clades. Three isolates were missing MATα1, potentially representing a second mating type. Signatures of positive selection were identified in every sequence type including enrichment for epithelial adhesins thought to facilitate fungal adhesin to human epithelial cells. In patent microevolution was identified from 7 sets of recurrent cases of candidiasis, revealing an enrichment for nonsynonymous and frameshift indels in cell surface proteins. Microevolution within patients also affected epithelial adhesins genes, and several genes involved in drug resistance including the ergosterol synthesis gene ERG4 and the echinocandin target FKS1/2, the latter coinciding with a marked drop in fluconazole minimum inhibitory concentration. In addition to nuclear genome diversity, the C. glabrata mitochondrial genome was particularly diverse, with reduced conserved sequence and conserved protein-encoding genes in all nonreference ST15 isolates. Together, this study highlights the genetic diversity within the C. glabrata population that may impact virulence and drug resistance, and 2 major mechanisms generating this diversity: microevolution and genetic exchange/recombination.
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Candida glabrata , Genoma Mitocondrial , Adulto , Antifúngicos/farmacología , Candida glabrata/genética , Farmacorresistencia Fúngica/genética , Genética de Población , Humanos , Virulencia/genéticaRESUMEN
'Hilarity and a good nature [and] a breezy cheerfulness help enormously in the study and in the practice of medicine,' said Sir William Osler, Regius Professor of Medicine at Oxford, pioneering medical educationalist, and arguably one of the greatest physicians of all time (Osler W. 1905 ). We present evidence that (1) Encouraging Learning, (2) Entertaining People, and (3) Having a Nice Time are dangerously powerful adjuncts to medical education. These are, by acronym, the ELEPHANT criteria. Encouraging is the motivating heart of the matter. Entertainment engages the mind and has been shown to enhance working memory and recall. Enjoyment is associated with deep learning, which comes with a whole host of benefits. However, learning in fear and misery can be an effective tool--but for other reasons--and the pessimistic personality type may respond badly to 'fun learning.' Even so, medical education that fulfills the ELEPHANT criteria can be an effective tool in training young doctors.
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Educación Médica , Felicidad , Aprendizaje , Estudiantes de Medicina , Enseñanza , Humanos , Satisfacción PersonalRESUMEN
The mechanisms regulating the synthesis of mRNA, cRNA, and viral genomic RNA (vRNA) by the influenza A virus RNA-dependent RNA polymerase are not fully understood. Previous studies in our laboratory have shown that virion-derived viral ribonucleoprotein complexes synthesize both mRNA and cRNA in vitro and early in the infection cycle in vivo. Our continued studies showed that de novo synthesis of cRNA in vitro is more sensitive to the concentrations of ATP, CTP, and GTP than capped-primer-dependent synthesis of mRNA. Using rescued recombinant influenza A/WSN/33 viruses, we now demonstrate that the 3'-terminal sequence of the vRNA promoter dictates the requirement for a high nucleoside triphosphate (NTP) concentration during de novo-initiated replication to cRNA, whereas this is not the case for the extension of capped primers during transcription to mRNA. In contrast to some other viral polymerases, for which only the initiating NTP is required at high concentrations, influenza virus polymerase requires high concentrations of the first three NTPs. In addition, we show that base pair mutations in the vRNA promoter can lead to nontemplated dead-end mutations during replication to cRNA in vivo. Based on our observations, we propose a new model for the de novo initiation of influenza virus replication.