Testing for Prohibited Substances in Rural Agricultural Show Exhibits: A Twenty-Three Year Experience.

The administration of prohibited substances has been used in agricultural show competitions and animal racing industries to gain unfair competitive advantages. We report the first large prospectively designed descriptive study of drug testing in four species (n = 1,598) over a 23 year period. 4.7% of tested exhibits returned positive results. Commonly detected substances included legitimate veterinary therapeutics such as the sedative acepromazine and the non-steroidal anti-inflammatory phenylbutazone. Targeted testing was more likely to return a positive result than random screening (50 vs 4.7% respectively) although numbers in this targeted sample were small (n = 12). Random drug testing programs were successful in detecting the minority of exhibits using prohibited substances although a wide variety of drugs were found to be used. Further vigilance and research is required in an ever-changing competitive climate to remain at the forefront of detecting new medications in animal show competitions.

Using Coronary Artery Calcium Scoring as Preventative Health Tool to Reduce the High Burden of Cardiovascular Disease in Indigenous Australians.

BACKGROUND: Indigenous Australians suffer higher rates of ischaemic heart disease resulting in premature mortality. Despite this, Indigenous Australians undergo less cardiovascular investigation and intervention than their non-Indigenous counterparts. Recent evidence suggests that computed tomography coronary angiography (CTCA) is not only able to accurately predict cardiovascular risk, but also results in reduced rates of myocardial infarction and cardiovascular death. METHODS: This is a prospective longitudinal study of patients in regional Australia referred for CTCA at a regional centre from 2012 to 2017. Patients were identified as Indigenous at registration. Results were recorded from formal radiology reports. Logistic regression was used to compare calcium score, as a measure of coronary artery disease burden in Indigenous and non-Indigenous patients. RESULTS: Indigenous patients are 2.8 times more likely to have a higher burden of coronary artery disease than non-Indigenous patients, even after accounting for the higher rate of cardiovascular risk factors in the Indigenous population (OR 2.77; p = 0.008). In the study population, Indigenous patients were well represented as compared to the background population. CONCLUSION: This is the first study of CTCA in an Indigenous Australian population, and one of the first using CTCA for an Indigenous population worldwide. It demonstrates a higher burden of cardiovascular disease for Indigenous Australians, independent of the higher rate of cardiovascular risk factors. Access to CTCA presents an opportunity to reduce the rate of myocardial infarction and early mortality in the Indigenous Australian population.

Understanding the professional satisfaction of hospital trainees in Australia.

CONTEXT: Ensuring that specialty trainees are professionally satisfied is not only important from the point of view of trainee well-being, but is also critical if health systems are to retain doctors. Despite this, little systematic research in specialist trainees has identified policy-amenable factors correlated with professional satisfaction. This study examined factors associated with trainee professional satisfaction in a national Australian cohort. METHODS: This study used 2008-2015 data from the Medicine in Australia: Balancing Employment and Life (MABEL) survey, a national study of doctor demographics, characteristics and professional and personal satisfaction. Our study examined specialist trainees using a repeat cross-sectional method pooling first responses across all waves. A multivariate logistic regression analysis was used to assess correlates with professional satisfaction. RESULTS: The three factors most strongly correlated with professional satisfaction were feeling well supported and supervised by consultants (odds ratio [OR] 2.59, 95% confidence interval [CI] 2.42-2.77), having sufficient study time (OR 1.54, 95% CI 1.40-1.70) and self-rated health status (OR 1.65, 95% CI 1.53-1.80). Those working >56 hours per week were significantly less professionally satisfied (OR 0.76, 95% CI 0.70-0.84) compared with those working the median work hours (45-50 hours per week). Those earning in the lower quintiles, those earlier in their training and those who had studied at overseas universities were also significantly less likely to be satisfied. CONCLUSIONS: Our study suggests that good clinical supervision and support, appropriate working hours and supported study time directly impact trainee satisfaction, potentially affecting the quality of clinical care delivered by trainees. Furthermore, the needs of junior trainees, overseas graduates and those working >56 hours per week should be given particular consideration when developing well-being and training programmes.

Attracting junior doctors to rural centres: A national study of work-life conditions and satisfaction.

OBJECTIVE: Junior doctors, in their first four years of medical work, are an important part of the health care team. Attracting and retaining these doctors to rural areas underpins the development of the future rural workforce. This is the first national-scale study about satisfaction of junior doctors, based on their work location, to inform recruitment and retention. DESIGN: Repeat cross-sectional data 2008 and 2015, pooled for analysis. SETTING: Medicine in Australia: Balancing Employment and Life survey. PARTICIPANTS: First responses of 4581 pre-vocational doctors working as interns up to their fourth postgraduate year. MAIN OUTCOME MEASURES: Differences between metropolitan and rural respondents in satisfaction and positivity on two inventories. RESULTS: Overall work satisfaction was approximately 85% amongst rural and metropolitan junior doctors, but controlling for other factors rural junior doctors had significantly higher overall satisfaction. Rural junior doctors were significantly more satisfied with their work-life balance, ability to obtain desired leave and leave at short notice, personal study time and access to leisure interests compared with metropolitan junior doctors. Metropolitan junior doctors were more satisfied with the network of doctors supporting them and the opportunities for family. CONCLUSION: While both metropolitan and rural junior doctors are generally satisfied, many professional and personal aspects of satisfaction differ considerably by work location. In order to attract early career doctors, the benefits of rural work should be emphasised and perceived weaknesses mitigated.

Partial empty sella in a woman with cerebral venous sinus thrombosis: A rare presentation of polycythaemia rubra vera.

We report the case of a 59 year old woman who presented with a six week history of worsening bifrontal headache. On CT brain the only abnormal finding was a partially empty sella potentially indicative of increased intracranial pressure. MRI found a large cerebral venous sinus thrombosis in the superior sagittal sinus. Blood tests and a bone marrow biopsy revealed a diagnosis of JAK2 positive primary polycythaemia rubra vera. The lack of sensitivity and specificity of CT in the diagnosis of CVST should engender a low threshold for MRI in patients with risk factors and/or non-diagnostic abnormalities on initial CT. Management of this dual pathology involves both the immediate treatment of the thrombus with heparin bridging to warfarin and the long treatment for polycythaemia involving repeat venesections and cytoreductive therapy.

Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: a potential mechanism for diastolic dysfunction.

AIMS: Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using (31)Phosphorus MR Spectroscopy ((31)P MRS). We hypothesized that cardiac energetics are further impaired acutely during exercise in HCM and that this would have important functional consequences. METHODS AND RESULTS: (31)P MRS was performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM: 1.71 ± 0.35, normal 2.14 ± 0.35 P < 0.0001). During exercise, there was a further reduction in PCr/ATP in HCM (1.56 ± 0.29, P = 0.02 compared with rest) but not in normals (2.16 ± 0.26, P = 0.98 compared with rest). There was no correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at rest (r = 0.48, P = 0.02) and stress (r = 0.53, P = 0.01). CONCLUSION: During exercise, the pre-existing energetic deficit in HCM is further exacerbated independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in keeping with the change at the myofilament level. We offer a potential explanation for exercise-related diastolic dysfunction in HCM.

Myocardial steatosis and left ventricular contractile dysfunction in patients with severe aortic stenosis.

BACKGROUND: Aortic stenosis (AS) leads to left ventricular (LV) hypertrophy and dysfunction. We hypothesized that cardiac steatosis is involved in the pathophysiology and also assessed whether it is reversible after aortic valve replacement. METHODS AND RESULTS: Thirty-nine patients with severe AS (symptomatic=25, asymptomatic=14) with normal LV ejection fraction and no significant coronary artery disease and 20 age- and sex-matched healthy controls underwent cardiac 1H-magnetic resonance spectroscopy and imaging for the determination of steatosis (myocardial triglyceride content) and cardiac function, including circumferential strain (measured by magnetic resonance tagging). Strain was lower in both symptomatic and asymptomatic AS (-16.4 ± 2.5% and -18.1 ± 2.9%, respectively, versus controls -20.7 ± 2.0%, both P<0.05). Myocardial steatosis was found in both symptomatic and asymptomatic patients with AS (0.89 ± 0.42% in symptomatic AS; 0.75 ± 0.36% in asymptomatic AS versus controls 0.45 ± 0.17, both P<0.05). Importantly, multivariable analysis indicated that steatosis was an independent correlate of impaired LV strain. Spectroscopic measurements of myocardial triglyceride content correlated significantly with histological analysis of biopsies obtained during aortic valve replacement. At 8.0 ± 2.1 months after aortic valve replacement, steatosis and strain had recovered toward normal. CONCLUSIONS: Pronounced myocardial steatosis is present in severe AS, regardless of symptoms, and is independently associated with the degree of LV strain impairment. Myocardial triglyceride content measured by magnetic resonance spectroscopy correlates with histological quantification. Steatosis and strain impairment are reversible after aortic valve replacement. Our findings suggest a novel pathophysiological mechanism in AS, myocardial steatosis, which may be amenable to treatment, thus potentially delaying onset of LV dysfunction.

Comprehensive cardiac magnetic resonance imaging and spectroscopy reveal a high burden of myocardial disease in HIV patients.

BACKGROUND: HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy. METHODS AND RESULTS: Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels (P <0.003) and 74% higher median plasma triglyceride levels (both P<0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects (P<0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders. CONCLUSIONS: Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.

Blunted myocardial oxygenation response during vasodilator stress in patients with hypertrophic cardiomyopathy.

OBJECTIVES: This study sought to assess myocardial perfusion and tissue oxygenation during vasodilator stress in patients with overt hypertrophic cardiomyopathy (HCM), as well as in HCM mutation carriers without left ventricular (LV) hypertrophy, and to compare findings to those in athletes with comparable hypertrophy and normal controls. BACKGROUND: Myocardial perfusion under vasodilator stress is impaired in patients with HCM. Whether this is associated with impaired myocardial oxygenation and tissue ischemia is unknown. Furthermore, it is not known whether perfusion and oxygenation are impaired in HCM mutation carriers without left ventricular hypertrophy (LVH). METHODS: A total of 27 patients with overt HCM, 10 HCM mutation carriers without LVH, 11 athletes, and 20 healthy controls underwent cardiovascular magnetic resonance (CMR) scanning at 3-T. Myocardial function, perfusion (perfusion reserve index [MPRI]), and oxygenation (blood-oxygen level dependent signal intensity [SI] change) under adenosine stress were assessed. RESULTS: MPRI was significantly reduced in HCM (1.3 ± 0.1) compared to controls (1.8 ± 0.1, p < 0.001) and athletes (2.0 ± 0.1, p < 0.001), but remained normal in HCM mutation carriers without LVH (1.7 ± 0.1; p = 0.61 vs. controls, p = 0.02 vs. overt HCM). Oxygenation response was attenuated in overt HCM (SI change 6.9 ± 1.4%) compared to controls (18.9 ± 1.4%, p < 0.0001) and athletes (18.7 ± 2.0%, p < 0.001). Interestingly, HCM mutation carriers without LVH also showed an impaired oxygenation response to adenosine (10.4 ± 2.0%; p = 0.001 vs. controls, p = 0.16 vs. overt HCM, p = 0.003 vs. athletes). CONCLUSIONS: In overt HCM, both perfusion and oxygenation are impaired during vasodilator stress. However, in HCM mutation carriers without LVH, only oxygenation is impaired. In athletes, stress perfusion and oxygenation are normal. CMR assessment of myocardial oxygenation has the potential to become a novel risk factor in HCM.

Myocardial tissue characterization using magnetic resonance noncontrast t1 mapping in hypertrophic and dilated cardiomyopathy.

BACKGROUND: Noncontrast magnetic resonance T1 mapping reflects a composite of both intra- and extracellular signal. We hypothesized that noncontrast T1 mapping can characterize the myocardium beyond that achieved by the well-established late gadolinium enhancement (LGE) technique (which detects focal fibrosis) in both hypertrophic (HCM) and dilated (DCM) cardiomyopathy, by detecting both diffuse and focal fibrosis. METHODS AND RESULTS: Subjects underwent Cardiovascular Magnetic Resonance imaging at 3T (28 HCM, 18 DCM, and 12 normals). Matching short-axis slices were acquired for cine, T1 mapping, and LGE imaging (0.1 mmol/kg). Circumferential strain was measured in the midventricular slice, and (31)P magnetic resonance spectroscopy was acquired for the septum of the midventricular slice. Mean T1 relaxation time was increased in HCM and DCM (HCM 1209±28 ms, DCM 1225±42 ms, normal 1178±13 ms, P<0.05). There was a weak correlation between mean T1 and LGE (r=0.32, P<0.001). T1 values were higher in segments with LGE than in those without (HCM with LGE 1228±41 ms versus no LGE 1192±79 ms, P<0.01; DCM with LGE 1254±73 ms versus no LGE 1217±52 ms, P<0.01). However, in both HCM and DCM, even in segments unaffected by LGE, T1 values were significantly higher than normal (P<0.01). T1 values correlated with disease severity, being increased as wall thickness increased in HCM; conversely, in DCM, T1 values were highest in the thinnest myocardial segments. T1 values also correlated significantly with circumferential strain (r=0.42, P<0.01). Interestingly, this correlation remained statistically significant even for the slices without LGE (r=0.56, P=0.04). Finally, there was also a statistically significant negative correlation between T1 values and phosphocreatine/adenosine triphosphate ratios (r=-0.59, P<0.0001). CONCLUSIONS: In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.

Exercise training in dilated cardiomyopathy improves rest and stress cardiac function without changes in cardiac high energy phosphate metabolism.

OBJECTIVE: To determine the effects of short-term exercise training on cardiac function and metabolism during rest and physical exercise in patients with heart failure from dilated cardiomyopathy (DCM). DESIGN: Patients with DCM (n=15, age 58±2 years, NYHA class I-III) were studied before and after 8 weeks of cycle exercise for 20 min, five times per week. MAIN OUTCOME MEASURES: Cardiac volumes, function and high energy phosphate metabolism were measured using cardiac magnetic resonance during rest and 7 min of acute physical exercise (leg-raising). RESULTS: At baseline, average left ventricular ejection fraction (LVEF) was 38±3%, which did not alter during 7 min of exercise. After 8 weeks of home exercise training, there was a 16% improvement in resting LVEF to 44±3% (p<0.01). Training caused a further 20% improvement in LVEF (p<0.05) during acute physical exercise. There was a negative correlation between subjects' baseline level of exercise and change in LVEF (r=-0.67, p<0.05), with sedentary patients having the greatest improvement. Cardiac phosphocreatine (PCr) to ATP ratio did not change during acute physical exercise or after exercise training. CONCLUSIONS: Short-term exercise training improves resting LVEF and LVEF with acute physical exercise with sedentary patients having the greatest improvement. There were no changes in cardiac PCr to ATP, before or after exercise training, suggesting that the improved cardiac function was not caused by improved energetics. Therefore, peripheral factors likely underlie the improved cardiac function in patients with heart failure after short-term exercise.

Prevalence of cardiomyopathy in asymptomatic patients with left bundle branch block referred for cardiovascular magnetic resonance imaging.

The diagnostic evaluation of patients with isolated left bundle branch block (LBBB) is challenging due to limitations of several non-invasive tests. Our aim was to evaluate the diagnostic value of cardiovascular magnetic resonance (CMR) in asymptomatic patients with LBBB. Sixty-one asymptomatic patients with complete LBBB who were referred for CMR from January 2005 to November 2010 were identified. 29 patients (18 men) had normal echocardiograms (echo) whereas 25 (18 men) had abnormal findings on echo. Six had no echo and one had poor echo windows, and these patients were excluded from further analysis. Patients with cardiac symptoms or known coronary artery disease at the time of referral were also excluded. Of the 29 patients with normal echo, 9 (31%) were found to have pathological findings on CMR. The most common abnormalities were dilated cardiomyopathy-DCM (n = 6, 21%) followed by left ventricular hypertrophy (n = 2, 7%). Of the 25 patients who had an abnormal echo, CMR confirmed the diagnosis in 19 (76%) and provided clinically relevant additional information in 13 (52%) subjects. Of these 13 patients, 9 (69%) had characteristic patterns of myocardial late gadolinium enhancement (8 mid-wall and 1 patchy distribution consistent with DCM and cardiac sarcoid, respectively). CMR detects sub-clinical cardiomyopathy in a third of asymptomatic patients with LBBB despite normal echocardiograms. In those with abnormal echocardiograms, CMR provides additional clinically relevant information in over 50% of patients, including a high prevalence of mid-wall fibrosis in patients with impaired left ventricular function. These findings support the use of CMR as a valuable adjunct to conventional investigations in asymptomatic LBBB.

Clinical cardiac magnetic resonance spectroscopy.

Cardiac magnetic resonance spectroscopy (MRS) is a noninvasive tool for the assessment of myocardial metabolism, without the use of radiation or intravenous contrast agents. Using the intrinsic magnetic resonance signals from nuclei, including (31)Phosphorus, (1)Hydrogen, (23)Sodium, and (13)Carbon and, more recently, hyperpolarization techniques, MRS provides a comprehensive metabolic assessment of cardiac muscle. This highly versatile technique has provided insights into the pathophysiology of cardiac metabolism in a wide range of conditions, including ischemic heart disease, heart failure, genetic cardiomyopathies, heart transplantation, hypertensive heart disease, valvular heart disease, and diabetes. In addition, MRS has value in the assessment of prognosis and for monitoring therapeutic strategies in heart failure. However, because of the low temporal and spatial resolution of the technique, MRS has so far been limited to research applications. With higher field strength magnets and novel hyperpolarization techniques, the promise of using MRS for clinical applications may eventually be fulfilled.

Identification of a structurally distinct CD101 molecule encoded in the 950-kb Idd10 region of NOD mice.

Genes affecting autoimmune type 1 diabetes susceptibility in the nonobese diabetic (NOD) mouse (Idd loci) have been mapped using a congenic strain breeding strategy. In the present study, we used a combination of BAC clone contig construction, polymorphism analysis of DNA from congenic strains, and sequence mining of the human orthologous region to generate an integrated map of the Idd10 region on mouse chromosome 3. We found seven genes and one pseudogene in the 950-kb Idd10 region. Although all seven genes in the interval are Idd10 candidates, we suggest the gene encoding the EWI immunoglobulin subfamily member EWI-101 (Cd101) as the most likely Idd10 candidate because of the previously reported immune-associated properties of the human CD101 molecule. Additional support for the candidacy of Cd101 is the presence of 17 exonic single-nucleotide polymorphisms that differ between the NOD and B6 sequences, 10 causing amino acid substitutions in the predicted CD101 protein. Four of these 10 substitutions are nonconservative, 2 of which could potentially alter N-linked glycosylation. Considering our results together with those previous reports that antibodies recognizing human CD101 modulate human T-cell and dendritic cell function, there is now justification to test whether the alteration of CD101 function affects autoimmune islet destruction.