Uptake of the Australian Heart Health Check before and after the COVID-19 pandemic outbreak.

BACKGROUND AND OBJECTIVES: In 2019, a 'Heart Health Check' Medicare Benefit Schedule (MBS) item (699) was introduced to support cardiovascular risk assessment. This study sought to determine the uptake of Item 699 and changes to existing health assessment item claims, before and after the COVID­19 outbreak. METHOD: National MBS data for health assessment items were analysed for adults aged ≥35 years. RESULTS: Item 699 accounted for 9% of health assessment item claims since its introduction. Claims for pre-existing health assessment items were virtually unchanged (1% increase) after Item 699 was introduced. Overall, there were 68,967 fewer health assessment item claims (7% decrease) after the COVID-19 outbreak and Item 699 had the greatest decline in claims (27% reduction). DISCUSSION: Uptake of Item 699 accounted for 9% of health assessment item claims since its introduction. COVID-19 restrictions coincided with a decline in all health assessment item claims, particularly for Item 699.

Treatment with Multiple Therapeutic Classes of Medication Is Associated with Survival after Stroke.

INTRODUCTION: Treatment with several therapeutic classes of medication is recommended for secondary prevention of stroke. We analyzed the associations between the number of classes of prevention medications supplied within 90 days after discharge for ischemic stroke (IS)/transient ischemic attack (TIA) and survival. METHODS: This is a retrospective cohort study of adults with first-ever IS/TIA (2010-2014) from the Australian Stroke Clinical Registry individually linked with data from national pharmaceutical and Medicare claims. Exposure was the number of classes of recommended medications, i.e., blood pressure-lowering, antithrombotic, or lipid-lowering agents, supplied to patients within 90 days after discharge for IS/TIA. The longitudinal association between the number of classes of medications and survival was evaluated with Cox proportional hazards regression models using the landmark approach. A landmark date of 90 days after hospital discharge was used to separate exposure and outcome periods, and only patients who survived until this date were included. RESULTS: Of 8,429 patients (43% female, median age 74 years, 80% IS), 607 (7%) died in the year following 90 days after discharge. Overall, 56% of patients were supplied all 3 classes of medications, 28% 2 classes of medications, 11% 1 class of medications, and 5% no class of medications. Compared to patients supplied all 3 medication classes, adjusted hazard ratios for all-cause mortality ranged from 1.43 (95% confidence interval [CI]: 1.18-1.72) in those supplied 2 medication classes to 2.04 (95% CI: 1.44-2.88) in those supplied with no medication class. DISCUSSION/CONCLUSION: Treatment with all 3 classes of guideline-recommended medications within 90 days after discharge was associated with better survival. Ongoing efforts are required to ensure optimal pharmacological intervention for secondary prevention of stroke.

Optimal Measures for Primary Care Physician Encounters after Stroke and Association with Survival: A Data Linkage Study.

BACKGROUND AND PURPOSE: Primary care physicians (PCPs) provide ongoing management after stroke. However, little is known about how best to measure physician encounters with reference to longer term outcomes. We aimed to compare methods for measuring regularity and continuity of PCP encounters, based on survival following stroke using linked healthcare data. METHODS: Data from the Australian Stroke Clinical Registry (2010-2014) were linked with Australian Medicare claims from 2009 to 2016. Physician encounters were ascertained within 18 months of discharge for stroke. We calculated three separate measures of continuity of encounters (consistency of visits with primary physician) and three for regularity of encounters (distribution of service utilization over time). Indices were compared based on 1-year survival using multivariable Cox regression models. The best performing measures of regularity and continuity, based on model fit, were combined into a composite "optimal care" variable. RESULTS: Among 10,728 registrants (43% female, 69% aged ≥65 years), the median number of encounters was 17. The measures most associated with survival (hazard ratio [95% confidence interval], Akaike information criterion [AIC], and Bayesian information criterion [BIC]) were the Continuity of Care Index (COCI, as a measure of continuity; 0.88 [0.76-1.02], p = 0.099, AIC = 13,746, BIC = 13,855) and our persistence measure of regularity (encounter at least every 6 months; 0.80 [0.67-0.95], p = 0.011, AIC = 13,742, BIC = 13,852). Our composite measure, persistent plus COCI ≥80% (24% of registrants; 0.80 [0.68-0.94], p = 0.008, AIC = 13,742, BIC = 13,851), performed marginally better than our persistence measure alone. CONCLUSIONS: Our persistence measure of regularity or composite measure may be useful when measuring physician encounters following stroke.

Applying a framework to assess the impact of cardiovascular outcomes improvement research.

BACKGROUND: Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016-2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research. METHODS: We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients. RESULTS: By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery. CONCLUSIONS: We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.

Evaluation of the effects of the T-type calcium channel enhancer SAK3 in a rat model of TAF1 deficiency.

The TATA-box binding protein associated factor 1 (TAF1) is part of the TFIID complex that plays a key role during the initiation of transcription. Variants of TAF1 are associated with neurodevelopmental disorders. Previously, we found that CRISPR/Cas9 based editing of the TAF1 gene disrupts the morphology of the cerebral cortex and blunts the expression as well as the function of the CaV3.1 (T-type) voltage gated calcium channel. Here, we tested the efficacy of SAK3 (ethyl 8'-methyl-2', 4-dioxo-2-(piperidin-1-yl)-2'H-spiro [cyclopentane-1, 3'-imidazo [1, 2-a] pyridine]-2-ene-3-carboxylate), a T-type calcium channel enhancer, in an animal model of TAF1 intellectual disability (ID) syndrome. At post-natal day 3, rat pups were subjected to intracerebroventricular (ICV) injection of either gRNA-control or gRNA-TAF1 CRISPR/Cas9 viruses. At post-natal day 21, the rat pups were given SAK3 (0.25 mg/kg, p.o.) or vehicle for 14 days (i.e. till post-natal day 35) and then subjected to behavioral, morphological, and molecular studies. Oral administration of SAK3 (0.25 mg/kg, p.o.) significantly rescued locomotion abnormalities associated with TAF1 gene editing. SAK3 treatment prevented the loss of cortical neurons and GFAP-positive astrocytes observed after TAF1 gene editing. In addition, SAK3 protected cells from apoptosis. SAK3 also restored the Brain-derived neurotrophic factor/protein kinase B/Glycogen Synthase Kinase 3 Beta (BDNF/AKT/GSK3ß) signaling axis in TAF1 edited animals. Finally, SAK3 normalized the levels of three GSK3ß substrates - CaV3.1, FOXP2, and CRMP2. We conclude that the T-type calcium channel enhancer SAK3 is beneficial against the deleterious effects of TAF1 gene-editing, in part, by stimulating the BDNF/AKT/GSK3ß signaling pathway.

Dynamic and Sex-Specific Changes in Gonadotropin-Releasing Hormone Neuron Activity and Excitability in a Mouse Model of Temporal Lobe Epilepsy.

Reproductive endocrine disorders are prominent comorbidities of temporal lobe epilepsy (TLE) in both men and women. The neural mechanisms underlying these comorbidities remain unclear, but hypothalamic gonadotropin-releasing hormone (GnRH) neurons may be involved. Here, we report the first direct demonstrations of aberrant GnRH neuron function in an animal model of epilepsy. Recordings of GnRH neuron firing and excitability were made in acute mouse brain slices prepared two months after intrahippocampal injection of kainate (KA) or control saline, a well-established TLE model in which most females develop comorbid estrous cycle disruption. GnRH neurons from control females showed elevated firing and excitability on estrus compared with diestrus. By contrast, cells from KA-injected females that developed prolonged, disrupted estrous cycles (KA-long) showed the reverse pattern. Firing rates of cells from KA-injected females that maintained regular cycles (KA-regular) were not different from controls on diestrus, but were reduced on estrus. In KA-injected males, only GnRH neurons in the medial septum displayed elevated firing. In contrast to the diestrus versus estrus and sex-specific changes in firing, GnRH neuron intrinsic excitability was elevated in all KA-injected groups, indicating a role for afferent synaptic and neuromodulatory inputs in shaping overall changes in firing activity. Furthermore, KA-injected females showed cycle-stage-specific changes in circulating sex steroids on diestrus and estrus that also differed between KA-long and KA-regular groups. Together, these findings reveal that the effects of epilepsy on the neural control of reproduction are dynamic across the estrous cycle, distinct in association with comorbid estrous cycle disruption severity, and sex-specific.

The yin and yang of KV channels in cerebral small vessel pathologies.

Cerebral SVDs encompass a group of genetic and sporadic pathological processes leading to brain lesions, cognitive decline, and stroke. There is no specific treatment for SVDs, which progress silently for years before becoming clinically symptomatic. Here, we examine parallels in the functional defects of PAs in CADASIL, a monogenic form of SVD, and in response to SAH, a common type of hemorrhagic stroke that also targets the brain microvasculature. Both animal models exhibit dysregulation of the voltage-gated potassium channel, KV 1, in arteriolar myocytes, an impairment that compromises responses to vasoactive stimuli and impacts CBF autoregulation and local dilatory responses to neuronal activity (NVC). However, the extent to which this channelopathy-like defect ultimately contributes to these pathologies is unknown. Combining experimental data with computational modeling, we describe the role of KV 1 channels in the regulation of myocyte membrane potential at rest and during the modest increase in extracellular potassium associated with NVC. We conclude that PA resting membrane potential and myogenic tone depend strongly on KV 1.2/1.5 channel density, and that reciprocal changes in KV channel density in CADASIL and SAH produce opposite effects on extracellular potassium-mediated dilation during NVC.

Effect of ensilation of potato on viability of Taenia hydatigena eggs.

A Taenia hydatigena model was used to assess the effect 0, 7, 14, 21, and 28 days of ensilation of minced potato on viability of tapeworm eggs. For infection of lambs, 2,000 T. hydatigena eggs were ensiled for 0, 7, 14, 21 and 28 days in minced potato at 22°C and fed to recently weaned lambs (29.9±0.76 kg). At slaughter, no cysticerci were recovered from lambs infected with eggs ensiled for 28 days while a mean of 5.0±5.0 cysticerci (0.25% of the initial egg dose) were recovered from lambs infected with eggs ensiled for 21 days. For lambs fed eggs ensiled for 0 days (control), 359.3±55.6 cysticerci were recovered (18.0% of the initial egg dose). Regression analysis revealed that a 99.9% reduction in viability was attained after 18.59 days of ensilation.

A randomised controlled trial of the effects of mindfulness practice on medical student stress levels.

OBJECTIVE: This study aimed to determine whether the practice of mindfulness reduces the level of stress experienced by senior medical students. METHODS: We carried out a multicentre, single-blinded, randomised controlled trial with intention-to-treat analysis in three clinical schools attached to the University of Tasmania, Hobart, Tasmania. Participants included 66 medical students in their final 2 years of study in 2009. Participants were block-randomised to either an intervention or a usual care control group. The intervention used an audio CD of guided mindfulness practice designed and produced for this trial. Participants were advised to use the intervention daily over the 8 weeks of the trial. All participants completed two self-report questionnaires, at baseline and at 8 weeks, respectively. The intervention group also completed a questionnaire at 16 weeks to provide follow-up data. The primary outcome measure was the difference over time in scores on the Perceived Stress Scale (PSS). The secondary outcome measure referred to differences over time in scores on the subscales of the Depression, Anxiety and Stress Scale (DASS). RESULTS: Mean baseline scores on the PSS and the stress component of the DASS were 15.7 (maximal score of 40) and 13.2 (maximal score of 42), respectively, both of which exceed scores in age-matched normative control data. Using multivariable analysis, participants in the intervention group demonstrated significant reductions in scores on the PSS (- 3.44, 95% confidence interval [CI] - 6.20 to - 0.68; p < 0.05) and the anxiety component of the DASS (- 2.82, 95% CI - 4.99 to - 0.64; p < 0.05). A borderline significant effect was demonstrated on the stress component of the DASS (- 3.69, 95% CI - 7.38 to 0.01; p = 0.05). Follow-up at 8 weeks post-trial revealed that the effect was maintained. CONCLUSIONS: Mindfulness practice reduced stress and anxiety in senior medical students. Stress is prevalent in medical students and can have adverse effects on both student health and patients. A simple, self-administered, evidence-based intervention now exists to manage stress in this at-risk population and should be widely utilised.

Role of reactive oxygen species (ROS) and JNKs in selenite-induced apoptosis in HepG2 cells.

Dietary selenium (Se) supplementation has been shown to be effective against reducing the risk of incidence of different human cancers. Selenium exists in both organic and inorganic forms. Different chemical forms of selenium metabolize differently in vivo, activate distinct molecular mechanisms and exhibit varying degree of anti-carcinogenicity in different cancer types. The effectiveness of a Se compound could also vary depending on the genetic background of the tumor cells. Therefore, understanding the molecular mechanism(s) by which different Se compounds exert their anti-tumorigenic effects is necessary for their use in cancer chemoprevention.

GP workforce participation in Tasmania.

BACKGROUND: Predicting future general practitioner workforce requires information about how demographic factors affect GP workforce participation. Regional differences might not be accounted for in national studies. The authors aimed to determine GP characteristics associated with workforce participation in Tasmania. METHODS: A self administered census of Tasmanian GPs measured GP demographics and the number of 3.5 hour sessions worked in 1 week in 2005. RESULTS: Four hundred and three GPs responded (76% response rate). Six percent of GPs were on leave at the time of the census. Age, gender and graduation outside of Australia, the United Kingdom or Ireland were associated with workforce participation, but rurality had no effect. The effect of age was modified by gender with women aged over 55 years being more likely to work full time (p=0.03). DISCUSSION: Factors affecting workforce participation may vary across regions. Predictions based on national models may need to be interpreted in the context of local circumstances.

Bivalirudin anticoagulation for a patient with hypercoagulable immune syndromes undergoing mitral valve surgery.

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Studies into the anticancer effects of selenomethionine against human colon cancer.

Colorectal cancer is the third most frequent fatal malignant neoplasm in the United States and is expected to cause significant morbidity and mortality. The recent recall of cyclooxygenase-2 inhibitors from clinical trials highlights the need to develop other agents for cancer chemoprevention trials. Intervention strategies with selenium compounds represent a viable option to reduce colon cancer. Here we discuss epidemiologic studies and ongoing clinical trials with selenium. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular bases for the anticancer effects of selenomethionine.

COX-2 inhibitors: exemplars of the drug-safety conundrum.

Using clinical trials to assess long-term drug safety is problematic; in Australia, simple data linkage based on Medicare numbers may provide useful monitoring information.

Chemoprevention of prostate cancer with selenium: an update on current clinical trials and preclinical findings.

Prostate cancer is the most common cancer diagnosed and the second leading cause of cancer-related deaths in men in the United States. The etiological factors that give rise to prostate cancer are not known. Therefore, it is not possible to develop primary intervention strategies to remove the causative agents from the environment. However, secondary intervention strategies with selenium (Se) compounds and other agents represent a viable option to reduce the morbidity and mortality of prostate cancer. In this review, we discuss ongoing clinical trials. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular basis for the anti-carcinogenic activity of both inorganic and organic forms of Se.

Prostate cancer and selenium.

The important progress achieved in the treatment of prostate cancer comes by exacting significant costs [11, 16-18, 20, 23, 25]. Currently, there is incomplete evidence that the radical interventions at hand significantly reduce the human costs of the disease. Surgery and radiotherapy induce substantial risks of incontinence and impotence. The PSA test has probably decreased the stage at which prostate cancer is diagnosed [15]. Nonetheless, the PSA is a means of earlier detection; it does not elucidate quantitatively distinct modes of treatment. The PSA test is not a means of prostate cancer prevention. The continuing incidence, morbidity, and mortality imposed by this disease strongly indicate that preventive strategies for its control are necessary. Chemoprevention with selenium and other agents offers a promising approach that is undergoing intensive investigation. Randomized trials underway at the authors' center are building on the important clinical trial results reported by Dr. Larry C. Clark. These studies will evaluate the activity of selenium at several points along a continuum ranging from cancerous prostatic tissue in men with diagnosed cancer to premalignant tissue in men with high-grade PIN to healthy tissue in high-risk men with negative biopsy to long-term effects on cancerous tissue in men with frank cancer. These trials will also offer an opportunity for preliminary evaluation of the mechanisms by which selenium treatment could result in the slower development or progression of prostate cancer.