Medical Education - Research Publications
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ItemNo Preview AvailableComprehensive Case-Control Study of Protective and Risk Factors for Buruli Ulcer, Southeastern Australia.(Centers for Disease Control and Prevention (CDC), 2023-10)To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.
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ItemNo Preview AvailableExploration of associations between occupational exposures and current adult eczema(BMJ PUBLISHING GROUP, 2023-10)OBJECTIVES: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults. METHODS: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations. RESULTS: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE. CONCLUSIONS: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence.
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ItemNo Preview AvailableMechanisms underlying the prolonged activation of the genioglossus following arousal from sleep(OXFORD UNIV PRESS INC, 2023-07-28)STUDY OBJECTIVES: Transient arousal from sleep has been shown to elicit a prolonged increase in genioglossus muscle activity that persists following the return to sleep and which may protect against subsequent airway collapse. We hypothesized that this increased genioglossal activity following return to sleep after an arousal is due to persistent firing of inspiratory-modulated motor units (MUs) that are recruited during the arousal. METHODS: Thirty-four healthy participants were studied overnight while wearing a nasal mask with pneumotachograph to measure ventilation and with 4 intramuscular genioglossus EMG electrodes. During stable N2 and N3 sleep, auditory tones were played to induce brief (3-15s) AASM arousals. Ventilation and genioglossus MUs were quantified before the tone, during the arousal and for 10 breaths after the return to sleep. RESULTS: A total of 1089 auditory tones were played and gave rise to 239 MUs recorded across arousal and the return to sleep in 20 participants (age 23±4.2 years and BMI 22.5±2.2kg/m 2). Ventilation was elevated above baseline during arousal and the first post-arousal breath (p<0.001). Genioglossal activity was elevated for 5 breaths following the return to sleep, due to increased firing rate and recruitment of inspiratory modulated MUs, as well as a small increase in tonic MU firing frequency. CONCLUSIONS: The sustained increase in genioglossal activity that occurs on return to sleep after arousal is primarily a result of persistent activity of inspiratory-modulated MUs, with a slight contribution from tonic units. Harnessing genioglossal activation following arousal may potentially be useful for preventing obstructive respiratory events.
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ItemNo Preview AvailableMultiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer(NATURE PORTFOLIO, 2023-03)High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole-genome duplication and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that evade therapy and ultimately overwhelm individual patients.
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ItemNo Preview AvailableThe role of syphilis self-testing as an additional syphilis testing approach in key populations: a systematic review and meta-analysis(ELSEVIER SCI LTD, 2023-09)BACKGROUND: Syphilis is causing epidemics in many countries. Syphilis self-testing (SST) has potential to increase testing and treatment coverage in the same manner as documented for self-testing of, for example, HIV, hepatitis C virus, and COVID-19. We aimed to synthesise current evidence on the utility of SST. METHODS: We conducted a systematic review and, where possible, meta-analysis. We searched MEDLINE, Embase, CINAHL, Scopus, and Web of Science for publications published from Jan 1, 2000, to Oct 13, 2022. We included publications with original data on any syphilis rapid tests, including dual HIV-syphilis tests. Study populations were not restricted. We used random-effects meta-analysis to calculate the pooled proportion of people offered SST who undertook the test. The systematic review was registered in PROSPERO (CRD42022302129). FINDINGS: In total, 40 499 citations were identified. 11 publications from seven studies from the USA, Zimbabwe, and China met eligibility criteria. Of those, four studies reported data from men who have sex with men and five studies used dual HIV-SST. Using data from one randomised controlled trial and three observational studies, the pooled proportion of people who received SST kits who undertook the test was 88% (95% CI 85-91). No studies provided data on the sensitivity or specificity of SST. Overall, user and provider preference for SST was high, with participants reporting convenience, privacy, rapid results, autonomy, trust in blood-based tests, decreased facility contact, and time savings, with individuals being able to correctly self-test. Publications from China reported that SST had lower costs per person tested than existing facility-based testing options. INTERPRETATION: Our review builds on the literature for self-testing across different disease areas and demonstrates that SST has the potential to reach underserved populations. As this review found that SST use was acceptable and feasible to implement, SST can be used as an additional syphilis testing approach. Since no data on the sensitivity and specificity of SST were found, further implementation research will be required to guide the best strategies for SST service delivery and future scale-up. FUNDING: WHO, Australian National Health and Medical Research Council, and Unitaid.
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ItemNo Preview AvailableThe relationship between long-term blood pressure variability and cortical thickness in older adults(ELSEVIER SCIENCE INC, 2023-09)High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.
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ItemNo Preview AvailableTrajectories of body mass index from early adulthood to late midlife and incidence of total knee arthroplasty for osteoarthritis: findings from a prospective cohort study(ELSEVIER SCI LTD, 2023-02-20)OBJECTIVE: To examine the association between body mass index (BMI) trajectories from early adulthood to late midlife and risk of total knee arthroplasty (TKA) for osteoarthritis. METHODS: 24,368 participants from the Melbourne Collaborative Cohort Study with weight collected during 1990-1994, 1995-1998, and 2003-2007, recalled weight at age 18-21 years, and height measured during 1990-1994 were included. Incident TKA from 2003 to 2007 to December 2018 was determined by linking cohort records to the National Joint Replacement Registry. RESULTS: Using group-based trajectory modelling, six distinct trajectories (TR) of BMI from early adulthood (age 18-21 years) to late midlife (approximately 62 years) were identified: lower normal to normal BMI (TR1; 19.7% population), normal BMI to borderline overweight (TR2; 36.7%), normal BMI to overweight (TR3; 26.8%), overweight to borderline obese (TR4; 3.5%), normal BMI to class 1 obesity (TR5; 10.1%), overweight to class 2 obesity (TR6; 3.2%). Over 12.4 years, 1,328 (5.4%) had TKA. The hazard ratios for TKA increased in all TR compared to TR1 [from TR2: 2.03 (95% CI 1.64-2.52) to TR6: 8.59 (6.44-11.46)]. 28.4% of TKA could be prevented if individuals followed the trajectory one lower, an average weight reduction of 8-12 kg from early adulthood to late midlife, saving $AUS 373 million/year. Most reduction would occur in TR2 (population attributable fraction 37.9%, 95% CI 26.7-47.3%) and TR3 (26.8%, 20.0-31.2%). CONCLUSIONS: Prevention of weight gain from young adulthood to late midlife in order to reduce overweight/obesity has the potential to significantly reduce the cost and burden of TKA.
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ItemNo Preview AvailableModified study designs to expand treatment options in personalised oncology: a multistakeholder view.(Elsevier BV, 2023-11)Personalised oncology, whereby patients are given therapies based on their molecular tumour profile, is rapidly becoming an essential part of optimal clinical care, at least partly facilitated by recent advances in next-generation sequencing-based technology using liquid- and tissue-based biopsies. Consequently, clinical trials have shifted in approach, from traditional studies evaluating cytotoxic chemotherapy in largely histology-based populations to modified, biomarker-driven studies (e.g. basket, umbrella, platform) of molecularly guided therapies and cancer immunotherapies in selected patient subsets. Such modified study designs may assess, within the same trial structure, multiple cancer types and treatments, and should incorporate a multistakeholder perspective. This is key to generating complementary, fit-for-purpose and timely evidence for molecularly guided therapies that can be used as proof-of-concept to inform further study designs, lead to approval by regulatory authorities and be used as confirmation of clinical benefit for health technology assessment bodies. In general, the future of cancer clinical trials requires a framework for the application of innovative technologies and dynamic design methodologies, in order to efficiently transform scientific discoveries into clinical utility. Next-generation, modified studies that involve the joint efforts of all key stakeholders will offer individualised strategies that ultimately contribute to globalised knowledge and collective learning. In this review, we outline the background and purpose of such modified study designs and detail key aspects from a multistakeholder perspective. We also provide methodological considerations for designing the studies and highlight how insights from already-ongoing studies may address current challenges and opportunities in the era of personalised oncology.
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ItemRecommendations from The Medical Education Editor(WILEY, 2022-09-06)
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ItemBilirubin as a new antioxidant in melasma(WILEY, 2022-11)BACKGROUND: Oxidative stress and its role in the pathogenesis of cutaneous diseases have been widely investigated. However, there are few studies that have solely assessed the contribution of intracellular antioxidants in the etiopathology of melasma. Furthermore, there are convincing reports about antioxidant properties of bilirubin (Bil) and uric acid (UA) in some skin disorders but not melasma. OBJECTIVE: This study aimed to determine serum levels of two major extracellular antioxidants (Bil and UA) levels in patients with melasma and their correlation with the severity and extent of the disease. METHODS: In this case-control study, the serum levels of bilirubin and uric acid of 50 melasma patients were compared with 50 healthy controls. Moreover, the correlation of serum concentrations of these antioxidants with the extent and severity of the disease were assessed. RESULTS: The serum concentration of Bil was significantly higher in the case group (p < 0.05). Furthermore, serum Bil level had a positive correlation with the extent of the melasma (correlation coefficient, +0.3; p < 0.05). No significant difference was found between the serum concentrations of UA between the study and control group. Neither Bil nor UA had a significant correlation with the severity of the disease. CONCLUSION: Oxidative stress may play a major role in the etiopathology of melasma and bilirubin, as an antioxidant, could be involved in the process of oxidative stress.