Medicine (Western Health) - Research Publications
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ItemThe use of component-wise gradient boosting to assess the possible role of cognitive measures as markers of vulnerability to pediatric bipolar disorder.(Informa UK Limited, 2019-03)BACKGROUND AND AIMS: Cognitive impairments are primary hallmarks symptoms of bipolar disorder (BD). Whether these deficits are markers of vulnerability or symptoms of the disease is still unclear. This study used a component-wise gradient (CGB) machine learning algorithm to identify cognitive measures that could accurately differentiate pediatric BD, unaffected offspring of BD parents, and healthy controls. METHODS: 59 healthy controls (HC; 11.19 ± 3.15 yo; 30 girls), 119 children and adolescents with BD (13.31 ± 3.02 yo, 52 girls) and 49 unaffected offspring of BD parents (UO; 9.36 ± 3.18 yo; 22 girls) completed the CANTAB cognitive battery. RESULTS: CGB achieved accuracy of 73.2% and an AUROC of 0.785 in classifying individuals as either BD or non-BD on a dataset held out for validation for testing. The strongest cognitive predictors of BD were measures of processing speed and affective processing. Measures of cognition did not differentiate between UO and HC. CONCLUSIONS: Alterations in processing speed and affective processing are markers of BD in pediatric populations. Longitudinal studies should determine whether UO with a cognitive profile similar to that of HC are at less or equal risk for mood disorders. Future studies should include relevant measures for BD such as verbal memory and genetic risk scores.
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ItemCare Coordination Can Reduce Unmet Needs of Persons With Severe and Persistent Mental Illness(FRONTIERS MEDIA SA, 2019-08-09)Introduction: Persons with severe and persistent mental illness (SPMI) have multiple and complex needs, many of which are not health related. Mental health services are unable to address these needs without collaboration with other agencies. In the absence of this collaboration, persons with SPMI often fall through the system cracks and are unlikely to experience recovery. Furthermore, previous studies have shown that unmet accommodation needs are associated with unmet needs in other areas. This study aimed to ascertain whether a care coordination model adopted in Australia's Partners in Recovery [PIR] initiative was able to reduce unmet needs in such persons and also if meeting accommodation needs were associated with meeting other needs. Methods: This was a longitudinal study where met and unmet needs of clients measured using the Camberwell Assessment of Needs Short Appraisal Schedule (CANSAS) were compared at enrolment and exit from the PIR initiative. Logistic regression was used to examine the association between change in accommodation needs and change in other CANSAS variables. Results: In total, 337 clients (66% of 508 clients) had both baseline and follow-up data and were seen within the time frame of 14 to 101 weeks. At baseline, the most frequently reported unmet needs were psychological distress, daytime activity, and company (89%, 72%, and 67%, respectively). At follow-up, these had decreased to 27%, 22%, and 22%, respectively. The proportions of clients with an unmet need at baseline who subsequently progressed to having that need met at follow-up ranged between 62% and over 90%. Change in accommodation needs from unmet to met was associated with changes in monetary needs and needs related to childcare, food, safety to self, education, and access to other services, with the greatest change seen for monetary needs (adjusted OR 2.87, 95% CI 1.76, 4.69). Conclusions: Reducing needs of persons with SPMI is the starting point of recovery and is a good indicator of psychiatric care. Care coordination is a useful way to address multiple and complex needs of persons with SPMI. While addressing needs, priority must be given to meeting accommodation needs.
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ItemA systems-centred approach to reducing medication error: Should pre-hospital providers and emergency departments dose children by age during resuscitation?(WILEY, 2019-11)The high-risk, high-stress and high-stakes environment of out-of-hospital or emergency department paediatric resuscitation is prone to human error, and medication errors are common. This could be contributing to the difference in survival rate of resuscitation in the out-of-hospital versus inpatient setting. Medication for children during resuscitation requires estimation of the child's weight and calculation of the corresponding drug dose. Whilst both of these steps can lead to error, calculation errors (including 10-fold errors) are much more common and harmful than weight errors. Previous solutions aim to optimise each stage of the medication dosing process. Currently, Australian guidelines suggest using the highly inaccurate original advanced paediatric life support formula, weight = 2 × (age + 4), to dose medications in these settings. This means age is converted to weight, which is then converted to dose. There is no evidence that this is causing harm to patients. Therefore, it could be suggested that age could safely be converted straight to dose according to preset doses. This eliminates the need for any weight estimation or dose calculation, thus reducing the potential for error and harm.
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ItemWorld Brain Day 2019; migraine - the painful truth(WILEY, 2019-11)
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ItemMuscarinic receptor 1 allosteric modulators stimulate colorectal emptying in dog, mouse and rat and resolve constipation(WILEY, 2019-11)BACKGROUND: Because M1 muscarinic receptors are expressed by enteric neurons, we investigated whether positive allosteric modulators of these receptors (M1PAMs) would enhance colorectal propulsion and defecation in dogs, mice, and rats. METHODS: The potencies of the M1PAMs, T662 or T523, were investigated using M1 receptor-expressing CHO cells. Effectiveness of M1PAMs on defecation was investigated by oral administration in mice and rats, by recording propulsive contractions in anaesthetized rats and by recording high amplitude propagating contractions in dogs. KEY RESULTS: PAM EC50 values in M1 receptor-expressing CHO cells were 0.7-1.8 nmol/L for T662 and 8-10 nmol/L for T523. The compounds had 1000-fold lower potencies as agonists. In anesthetized rats, both compounds elicited propulsive colorectal contractions, and in dogs, mice, and rats, oral administration increased fecal output. No adverse effects were observed in conscious animals. M1PAMs triggered propagated high amplitude contractions and caused defecation in dogs. Nerve-mediated contractions were enhanced in the isolated mouse colon. M1PAMs were equi-effective in rats with or without the pelvic nerves being severed. In two models of constipation in mice, opiate-induced constipation and constipation of aging, defecation was induced and constipation was reversed. CONCLUSION AND INFERENCES: M1PAMs act at targets sites in the colorectum to enhance colorectal propulsion. They are effective across species, and they reverse experimentally induced constipation. Previous studies have shown that they are safe in human. Because they provide an enhancement of physiological control rather than being direct agonists, they are predicted to provide effective treatment for constipation.
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ItemSubclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus(WILEY, 2019-08)BACKGROUND: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. AIM: To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. METHODS: Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. RESULTS: Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 μg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. CONCLUSION: Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.
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ItemSub-optimal treatment of paediatric migraine in an emergency department: An observational study(WILEY, 2019-10)OBJECTIVES: To describe treatment of children presenting to an Australian ED with a final ED diagnosis of migraine. METHODS: Planned substudy of a retrospective cohort study of the epidemiology of headache in children was done. Primary outcome of interest was treatment administered in the ED. RESULTS: Thirty-five children were studied. The most commonly used medications were non-steroidal anti-inflammatory drugs, paracetamol and ondansetron. Specific antimigraine therapy was used uncommonly. Fourteen percent of children received an opiate. CONCLUSION: Treatment of migraine in children was not consistent with the available evidence regarding agents' relative effectiveness. The use of opiates is concerningly high.
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