Water intoxication presenting as maternal and neonatal seizures: a case report.

Introduction We present an unusual case of fitting in the mother and newborn child, and the challenges faced in the management of their hyponatraemia due to water intoxication. Case presentation A previously well 37-year-old, primigravid Caucasian woman presented with features mimicking eclampsia during labour. These included confusion, reduced consciousness and seizures but without a significant history of hypertension, proteinuria or other features of pre-eclampsia. Her serum sodium was noted to be low at 111 mmol/litre as was that of her newborn baby. She needed anti-convulsants with subsequent intubation to stop the fitting and was commenced on a hypertonic saline infusion with frequent monitoring of serum sodium. There is a risk of long-term neurological damage from central pontine myelinolysis if the hyponatraemia is corrected too rapidly. Mother and baby went on to make a full recovery without any long-term neurological complications. Conclusion There is little consensus on the treatment of life-threatening hyponatraemia. Previous articles have outlined several possible management strategies as well as their risks. After literature review, an increase in serum sodium concentration of no more than 8–10 mmol/litre in 24 hours is felt to be safe but can be exceeded with extreme caution if life-threatening symptoms do not resolve. Formulae exist to calculate the amount of sodium needed and how much hypertonic intravenous fluid will be required to allow safer correction. We hypothesise the possible causes of hyponatraemia in this patient and underline its similarity in symptom presentation to eclampsia

Molecular epidemiology of Blastocystis sp.

University of Technology, Sydney. Faculty of Science.Blastocystis sp. is the most common enteric protist of the human gastrointestinal tract. There has been continual controversy over the role Blastocystis plays in causing gastrointestinal disease in humans. It has been suggested to be a pathogen or an opportunistic commensal and it has also been suggested that pathogenicity could be related to subtype (ST) determined by molecular methods. Until recently there was little known about this protist in terms of epidemiology, pathogenicity and treatment. Clinical diagnosis has traditionally been based on microscopy of wet preparations or permanent stains but there has recently been a push towards more sensitive techniques such as culture and polymerase chain reaction (PCR). The correct diagnosis of Blastocystis is necessary for epidemiological and clinical studies which will aid in determining the actual role of this parasite in the gut and in producing disease. Due to the lack of knowledge on the pathogenicity of this parasite, research into treatment options is limited. Metronidazole is a commonly used anti-parasitic drug that has frequently been used for Blastocystis treatment. There is evidence that this drug may not actually have much efficacy at all on Blastocystis and therefore be the incorrect treatment option. This project was designed to address some of the shortcomings in the literature surrounding this parasite. The overall aim of the project was to describe the molecular epidemiology of Blastocystis sp. from Australia and comment on the pathogenicity of Blastocystis in humans. To be able to determine the molecular epidemiology, it was necessary to use the correct diagnostic method and therefore the first aim of this study was to determine the best diagnostic technique used for the detection of Blastocystis (aim 1 of this study). Five different techniques were tested for their sensitivity for detecting Blastocystis and it was found that microscopy of a permanent stain was the least sensitive at detecting Blastocystis and that PCR was the most sensitive technique. Once the most sensitive diagnostic technique was established it was then possible to determine the prevalence of Blastocystis within the Sydney population from clinical samples (aim 2 of this study). It was found that there was a 19% incidence of Blastocystis in this population and seven subtypes (STs) were identified by sequencing- ST1, ST2, ST3, ST4, ST6, ST7 and ST8. ST3 was found to be the most common ST in this population. This study then investigated the prevalence of Blastocystis in animals and determined the STs present (aim 3 of this study). There were 38 different species of animal from seven different locations investigated for the presence of Blastocystis using PCR. There were 80 (18%) positive isolates from 18 species, and nine different STs were identified- ST1, ST2, ST3, ST4, ST5, ST7, ST11, ST12 and ST13. This is the first report of Blastocystis from the eastern grey kangaroo, red kangaroo, wallaroo, snow leopard and ostrich. This study has expanded current knowledge on the host range of Blastocystis. Blastocystis is associated with symptoms in humans similar to irritable bowel syndrome (IBS) such as bloating, diarrhoea and abdominal pain and therefore this study aimed to look at the relationship between Blastocystis and IBS (aim 4 of this study). This study showed that though there was not a significantly higher percentage of Blastocystis seen in the IBS group compared to the control group, there was a difference in the STs present with ST4 only present in the IBS group. This study also highlighted the need for full microbiological work-up before a diagnosis of IBS can be given as Blastocystis, along with other microbes, may actually be a contributor to the disease process. The final part of this study was to look at treatment options for Blastocystis. Due to the lack of knowledge on the pathogenicity of Blastocystis there have only been a few studies on treatment options and much more information is needed (aim 5 of this study). This study followed 18 patients with chronic Blastocystis infection who were treated with a variety of antimicrobials. It was seen that the most common drug treatment of choice, metronidazole, was not effective for the clearance of Blastocystis. This study also highlighted the chronic nature of Blastocystis infection in the absence of any other infectious agents. This study also carried out in vitro testing for four common human Blastocystis STs ( ST1, ST3, ST4 and ST8) against 12 commonly used antimicrobials- metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim- sulfamethoxazole (TMP-SMX), furazolidone, nitazoxonide, secnidazole, fluconazole, nyastatin and itraconazole. Cultures were maintained in media that was determined the best for Blastocystis growth from aim 1 of this study. From this in vitro study the lack of efficacy of commonly used antimicrobials for the treatment of Blastocystis was shown in particular metronidazole, paromomycin and a triple therapy combination of furazolidone, nitazoxanide and secnidazole. This study did show the efficacy of two drugs- TMP-SMX and ivermectin and suggested the use of these treatments instead of metronidazole. Each of these studies aims has furthered the knowledge on Blastocystis epidemiology, pathogenicity and treatment options. This is the largest molecular epidemiological study to be completed in Australia and also the largest animal study to be undertaken thus far. Overall, this PhD project has contributed significantly by enhancing and extending current knowledge on Blastocystis and will hopefully encourage future research on this fascinating protist

Multiple markers of cortical morphology reveal evidence of supragranular thinning in schizophrenia.

In vivo structural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organization, including relative contributions of different layers to sulcal and gyral thickness, regional patterns of variation in thickness of different layers across the cortical sheet and profiles of layer variation across functional hierarchies, it is possible to develop indirect morphological measures as markers of more specific cytoarchitectural changes. We developed four indirect measures sensitive to changes specifically occurring in supragranular cortical layers, and applied these to test the hypothesis that supragranular layers are disproportionately affected in schizophrenia. Our findings from the four different measures converge to indicate a predominance of supragranular thinning in schizophrenia, independent of medication and illness duration. We propose that these indirect measures offer novel ways of identifying layer-specific cortical changes, offering complementary in vivo observations to existing post-mortem studies.KW is supported by the University of Cambridge MB/PhD Programme and, together with KJW, by the Wellcome Trust. IMG by a Wellcome Trust Strategic Award (RNAG/260), and LR and PCF by the Bernard Wolfe Health Neuroscience Fund and Wellcome Trust

Can data in optometric practice be used to provide an evidence base for ophthalmic public health?

Purpose: The purpose of this paper is to investigate the potential of using primary care optometry data to support ophthalmic public health, research and policy making. Methods: Suppliers of optometric electronic patient record systems (EPRs) were interviewed to gather information about the data present in commercial software programmes and the feasibility of data extraction. Researchers were presented with a list of metrics that might be included in an optometric practice dataset via a survey circulated by email to 102 researchers known to have an interest in eye health. Respondents rated the importance of each metric for research. A further survey presented the list of metrics to 2000 randomly selected members of the College of Optometrists. The optometrists were asked to specify how likely they were to enter information about each metric in a routine sight test consultation. They were also asked if data were entered as free text, menus or a combination of these. Results: Current EPRs allowed the input of data relating to the metrics of interest. Most data entry was free text. There was a good match between high priority metrics for research and those commonly recorded in optometric practice. Conclusions: Although there were plenty of electronic data in optometric practice, this was highly variable and often not in an easily analysed format. To facilitate analysis of the evidence for public health purposes a UK based minimum dataset containing standardised clinical information is recommended. Further research would be required to develop suitable coding for the individual metrics included. The dataset would need to capture information from all sectors of the population to ensure effective planning of any future interventions

The metabolome as a diagnostic for maximal aerobic capacity during exercise in type 1 diabetes

\ua9 The Author(s) 2024.Aims/hypothesis: Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by V˙O2peak. Methods: Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3–200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by V˙O2peak test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% V˙O2peak) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity (V˙O2peak) during exercise in health and type 1 diabetes. Results: Maximal aerobic capacity (V˙O2peak) inversely correlated with HbA1c in the type 1 diabetes group (r2=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23 710−5) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity (V˙O2peak) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]). Conclusions/interpretation: The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes. Graphical Abstract: (Figure presented.)

The International Landscape of Medical Licensing Examinations: A Typology Derived From a Systematic Review

Background National licensing examinations (NLEs) are large-scale examinations usually taken by medical doctors close to the point of graduation from medical school. Where NLEs are used, success is usually required to obtain a license for full practice. Approaches to national licensing, and the evidence that supports their use, varies significantly across the globe. This paper aims to develop a typology of NLEs, based on candidacy, to explore the implications of different examination types for workforce planning. Methods A systematic review of the published literature and medical licensing body websites, an electronic survey of all medical licensing bodies in highly developed nations, and a survey of medical regulators. Results The evidence gleaned through this systematic review highlights four approaches to NLEs: where graduating medical students wishing to practice in their national jurisdiction must pass a national licensing exam before they are granted a license to practice; where all prospective doctors, whether from the national jurisdiction or international medical graduates, are required to pass a national licensing exam in order to practice within that jurisdiction; where international medical graduates are required to pass a licensing exam if their qualifications are not acknowledged to be comparable with those students from the national jurisdiction; and where there are no NLEs in operation. This typology facilitates comparison across systems and highlights the implications of different licensing systems for workforce planning. Conclusion The issue of national licensing cannot be viewed in isolation from workforce planning; future research on the efficacy of national licensing systems to drive up standards should be integrated with research on the implications of such systems for the mobility of doctors to cross borders