Change in health outcomes for First Nations children with chronic wet cough: rationale and study protocol for a multi-centre implementation science study.

BACKGROUND: In children, chronic wet cough may be a sign of underlying lung disease, including protracted bacterial bronchitis (PBB) and bronchiectasis. Chronic (> 4 weeks in duration) wet cough (without indicators pointing to alternative causes) that responds to antibiotic treatment is diagnostic of PBB. Timely recognition and management of PBB can prevent disease progression to irreversible bronchiectasis with lifelong consequences. However, detection and management require timely health-seeking by carers and effective management by clinicians. We aim to improve (a) carer health-seeking for chronic wet cough in their child and (b) management of chronic wet cough in children by clinicians. We hypothesise that implementing a culturally integrated program, which is informed by barriers and facilitators identified by carers and health practitioners, will result in improved lung health of First Nations children, and in the future, a reduced the burden of bronchiectasis through the prevention of the progression of protracted bacterial bronchitis to bronchiectasis. METHODS: This study is a multi-centre, pseudorandomised, stepped wedge design. The intervention is the implementation of a program. The program has two components: a knowledge dissemination component and an implementation component. The implementation is adapted to each study site using a combined Aboriginal Participatory Action Research and an Implementation Science approach, guided by the Consolidated Framework of Implementation Research. There are three categories of outcome measures related to (i) health (ii) cost, and (iii) implementation. We will measure health-seeking as the proportion of parents seeking help for their child in a 6-month period before the intervention and the same 6-month period (i.e., the same six calendar months) thereafter. The parent-proxy, Cough-specific Quality of Life (PC-QoL) will be the primary health-related outcome measure. DISCUSSION: We hypothesise that a tailored intervention at each site will result in improved health-seeking for carers of children with a chronic wet cough and improved clinician management of chronic wet cough. In addition, we expect this will result in improved lung health outcomes for children with a chronic wet cough. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry; ACTRN12622000430730 , registered 16 March 2022, Retrospectively registered.

The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment.

INTRODUCTION: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. METHODS: In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. RESULTS: Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (-7.8, -4.9 mmHg; P < .001). No serious adverse events were observed. DISCUSSION: This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

Health service delivery and workforce in northern Australia: a scoping review.

INTRODUCTION: Delivering health services and improving health outcomes of the 1.3 million people residing in northern Australia, a region spanning 3 million km2 across the three jurisdictions of Western Australia, Northern Territory and Queensland, presents specific challenges. This review addresses a need for systems level analysis of the issues influencing the coverage, quality and responsiveness of health services across this region by examining the available published literature and identifying key policy-relevant gaps. METHODS: A scoping review design was adopted with searches incorporating both peer-reviewed and grey literature (eg strategy documents, annual reports and budgets). Grey literature was predominantly sourced from websites of key organisations in the three northern jurisdictions, with peer-reviewed literature sourced from electronic database searches and reference lists. Key articles and documents were also contributed by health sector experts. Findings were synthesised and reported narratively using the WHO health system 'building blocks' to categorise the data. RESULTS: From the total of 324 documents and data sources included in the review following screening and eligibility assessment, 197 were peer-reviewed journal articles and 127 were grey literature. Numerous health sector actors across the north - comprising planning bodies, universities and training organisations, peak bodies and providers - deliver primary, secondary and tertiary healthcare and workforce education and training in highly diverse contexts of care. Despite many exemplar health service and workforce models in the north, this synthesis describes a highly fragmented sector with many and disjointed stakeholders and funding sources. While the many strengths of the northern health system include expertise in training and supporting a fit-for-purpose health workforce, health systems in the north are struggling to meet the health needs of highly distributed populations with poorly targeted resources and ill-suited funding models. Ageing of the population and rising rates of chronic disease and mental health issues, underpinned by complex social, cultural and environmental determinants of health, continue to compound these challenges. CONCLUSION: Policy goals about developing northern Australia economically need to build from a foundation of a healthy and productive population. Improving health outcomes in the north requires political commitment, local leadership and targeted investment to improve health service delivery, workforce stability and evidence-based strengthening of community-led comprehensive primary health care. This requires intersectoral collaboration across many organisations and the three jurisdictions, drawing from previous collaborative experiences. Further evaluative research, linking structure to process and outcomes, and responding to changes in the healthcare landscape such as the rapid emergence of digital technologies, is needed across a range of policy areas to support these efforts.

A mixed methodology, non-interventional study to evaluate the use of direct oral anticoagulants in UK clinical practice for patients with a first stroke associated with non-valvular atrial fibrillation: study protocol.

BACKGROUND: Treatment with anticoagulants, including direct oral anticoagulants (DOACs), should be considered for patients diagnosed with atrial fibrillation (AF) deemed at risk of ischaemic stroke. There are limited real world data related to the characteristics of patients with non-valvular AF who were not taking anticoagulants at the time of first ischaemic stroke and their subsequent DOAC treatment for the secondary prevention of stroke. Furthermore, little is known about patient adherence and experiences of DOAC treatment, especially for patients with non-valvular AF receiving DOAC therapy for the secondary prevention of stroke. METHODS: This is a UK mixed methodology, non-interventional study, involving retrospective and prospective medical record reviews and a prospective patient survey, in progress in six UK National Health Service secondary/tertiary care centres. The study comprises two groups of patients. Group 1 will include 300 eligible consenting patients with a first ischaemic stroke associated with non-valvular AF untreated with anticoagulants in the 12 months prior to stroke. Group 2 will include a subgroup of 150 patients from Group 1 initiated on one of the DOACs targeting activated Factor X (n = 50 on apixaban, n = 50 on edoxaban and n = 50 on rivaroxaban). The primary endpoint of the study is the CHA2DS2-VASc Risk Score prior to initiation of anticoagulation for patients included in Group 1. Secondary endpoints to be evaluated in Group 1 include patient demographics, clinical characteristics, relevant medical history, anticoagulant therapy initiated for secondary prevention of stroke, and relevant concomitant medication. Secondary endpoints to be evaluated in Group 2 include the time between stroke and DOAC initiation; prescribing of DOACs, other anticoagulants and concomitant medication; clinical assessments and hospital resource use; patient reported outcome measures, including the Morisky Medication Adherence Scale questionnaire and the Treatment Satisfaction Questionnaire for Medication. DISCUSSION: This mixed methodology study will provide new real world insights into the characteristics and management pathways and patient-reported experiences of this important group of patients. It is anticipated that the results of this study will provide the medical community and patients with important information to inform clinical decision-making and help facilitate meaningful improvements in the care of patients with non-valvular AF.

Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease.

BACKGROUND AND PURPOSE: Cerebral small-vessel disease is a major cause of cognitive impairment. Perivascular spaces (PvS) occur in small-vessel disease, but their relationship to cognitive impairment remains uncertain. One reason may be difficulty in distinguishing between lacunes and PvS. We determined the relationship between baseline PvS score and PvS volume with change in cognition over a 5-year follow-up. We compared this to the relationship between baseline lacune count and total lacune volume with cognition. In addition, we examined change in PvS volume over time. METHODS: Data from the prospective SCANS study (St Georges Cognition and Neuroimaging in Stroke) of patients with symptomatic lacunar stroke and confluent leukoaraiosis were used (n=121). Multimodal magnetic resonance imaging was performed annually for 3 years and neuropsychological testing annually for 5 years. Lacunes were manually identified and distinguished from PvS. PvS were rated using a validated visual rating scale, and PvS volumes calculated using T1-weighted images. Linear mixed-effect models were used to determine the impact of PvS and lacunes on cognition. RESULTS: Baseline PvS scores or volumes showed no association with cognitive indices. No change was detectable in PvS volumes over the 3 years. In contrast, baseline lacunes associated with all cognitive indices and predicted cognitive decline over the 5-year follow-up. CONCLUSIONS: Although a feature of small-vessel disease, PvS are not a predictor of cognitive decline, in contrast to lacunes. This study highlights the importance of carefully differentiating between lacunes and PvS in studies investigating vascular cognitive impairment.

Validation of Montreal Cognitive Assessment, MoCA, Alternate French Versions.

UNLABELLED: Objective background: The Montreal Cognitive Assessment (MoCA) is a questionnaire that has been developed to help physicians around the world diagnose a patient's cognitive ability. Available in multiple languages and for use in multiple countries worldwide, the goal of this study was to validate the alternate versions 2 and 3 of the French MoCA test to assist physicians in the detection of mild cognitive impairment (MCI), while decreasing the learning effect upon frequent testing. METHODS: A validation study was conducted at the MoCA Clinic and Institute in Québec, Canada. The subject population consisted of 25 patients diagnosed with MCI meeting Petersen criteria and 25 healthy subjects serving as the normal control (NC) group. Three MoCA test versions were administered in the French language in random order within one session. Scores obtained in all three versions in MCI and NC groups were assessed for reliability and consistency from one version to the next. RESULTS: On average, scores obtained in each subject group (MCI and NC) fell within their corresponding diagnostic ranges (score above 26 points for NC patients versus scores below 26 points for MCI patients). Difference in scores observed between the original French MoCA version and the two alternate versions in each subject cohort were minimal and not considered clinically significant. CONCLUSIONS: All three test versions of the French MoCA are considered equivalent in diagnostic reliability and consistency and contribute to decreasing the potential learning effect when patients are required to repeat the test frequently.

Hemichorea-hemiballism: a case report.

A 55-year-old woman with type 2 diabetes mellitus presented with abnormal left-sided movements of her arm and leg. Her initial CT scan of head showed a hyperintensity in the right basal ganglia. A 3 T MR scan of brain showed changes consistent with right basal ganglia haemorrhage. We diagnosed hemichorea-hemiballism syndrome. We treated her movement disorder with tetrabenazine and sulpiride and improved her glucose control. After 4 months, she still has mildly abnormal left-sided movements but can function independently again. In this article, we discuss her imaging and review the literature on hemichorea-hemiballism.

Responding to the AMR threat: data and information needs of stakeholders working in regional and remote Australia.

Our qualitative analysis of interviews with remote Australian healthcare professionals found that they require reliable, local antimicrobial resistance (AMR) data reflecting the geographical diversity of the population they serve. The optimal use of AMR data must consider challenges within this setting, including high staff turnover, limited diagnostic capacity, and antibiotic shortages.

Human Factors Validation of a Wearable, On-Body Infusor for Subcutaneous Administration of Furosemide.

Purpose: Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs). Methods: Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation. Results: Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity. Conclusion: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.

Cerebral microbleeds and cognition in patients with symptomatic small vessel disease.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are common in cerebral small vessel disease. They may cause cognitive impairment, possibly via white matter tract disruption but previous studies have produced inconsistent results. We determined whether CMB number and location are associated with impaired cognition in symptomatic small vessel disease and whether any association was independent of other magnetic resonance imaging markers of small vessel disease. METHODS: One hundred sixteen patients with lacunar stroke and radiological leukoaraiosis were studied. Neuropsychological assessment was performed. CMBs on gradient echo images were assessed using the Brain Observer Microbleed Rating Scale criteria. Magnetic resonance imaging measures, including diffusion tensor imaging, were also analyzed. Associations between cognitive function and the presence, number, and location of CMBs were determined. RESULTS: CMBs were present in 46 (39.7%) patients. CMB number correlated weakly with executive function (r=0.22; P=0.022) but not with other cognitive indices. CMBs count in the top decile (≥ 9 CMB, N=12) was more strongly associated with poor executive function; this association remained significant after controlling for T2-lesion load, brain volume, lacune count, and mean diffusivity (b=-0.51; P=0.043). CONCLUSIONS: In symptomatic small vessel disease, CMB number was weakly associated with executive dysfunction. There seemed to be a threshold effect with the association being largely accounted for by an association of impaired executive function with high CMB count. No association of CMBs with other cognitive domains, including processing speed, was found.

The aluminium content of infant formulas remains too high.

BACKGROUND: Recent research published in this journal highlighted the issue of the high content of aluminium in infant formulas. The expectation was that the findings would serve as a catalyst for manufacturers to address a significant problem of these, often necessary, components of infant nutrition. It is critically important that parents and other users have confidence in the safety of infant formulas and that they have reliable information to use in choosing a product with a lower content of aluminium. Herein, we have significantly extended the scope of the previous research and the aluminium content of 30 of the most widely available and often used infant formulas has been measured. METHODS: Both ready-to-drink milks and milk powders were subjected to microwave digestion in the presence of 15.8 M HNO3 and 30% w/v H2O2 and the aluminium content of the digests was measured by TH GFAAS. RESULTS: Both ready-to-drink milks and milk powders were contaminated with aluminium. The concentration of aluminium across all milk products ranged from ca 100 to 430 µg/L. The concentration of aluminium in two soya-based milk products was 656 and 756 µg/L. The intake of aluminium from non-soya-based infant formulas varied from ca 100 to 300 µg per day. For soya-based milks it could be as high as 700 µg per day. CONCLUSIONS: All 30 infant formulas were contaminated with aluminium. There was no clear evidence that subsequent to the problem of aluminium being highlighted in a previous publication in this journal that contamination had been addressed and reduced. It is the opinion of the authors that regulatory and other non-voluntary methods are now required to reduce the aluminium content of infant formulas and thereby protect infants from chronic exposure to dietary aluminium.

A national study into the rural and remote pharmacist workforce.

INTRODUCTION: As for many health professionals, distance presents an enormous challenge to pharmacists working in rural and remote Australia. Previous studies have identified issues relating to the size of the rural and remote pharmacist workforce, and a number of national initiatives have been implemented to promote the recruitment and retention of pharmacists in rural and remote locations. The aim of this study was to explore and describe the current rural and remote pharmacy workforce, and to identify barriers and drivers influencing rural and remote pharmacy practice. METHODS: A mixed-methods approach was used, which comprised a qualitative national consultation and a quantitative rural and remote pharmacist workforce survey. Semi-structured interviews (n=83) and focus groups (n=15, 143 participants) were conducted throughout Australia in 2009 with stakeholders with an interest in rural and remote pharmacy, practising rural/remote pharmacists and pharmacy educators, and as well as with peak pharmacy organizations, to explore the issues associated with rural/remote practice. Based on the findings of the qualitative work a 45-item survey was developed to further explore the relevance of the issues identified in the qualitative consultation. All registered Australian pharmacists practising in non-urban locations (RRMA 3-7, n=3,300) were identified and invited to participate in the study, with a response rate of 23.4%. RESULTS: The main themes identified from the qualitative consultation were the impact of national increases in the pharmacist workforce on rural/remote practice; the role of the regional pharmacy schools in contributing to the rural/remote workforce; and the perceptions of differences in pharmacist roles in rural/remote practice. The survey indicated that pharmacists practising in rural and remote locations were older than the national average (55.8 years versus 40 years). Differences in their professional role were seen in different pharmacy sectors, with hospital pharmacists spending significantly more time on the delivery of professional services and education and teaching, but less time on medication supply than community pharmacists. Rural/remote pharmacists were generally found to be satisfied with their current role. The main 'satisfiers' reported were task variety, customer appreciation, use of advanced skills, appropriate remuneration, happiness in their work location, sound relationships with other pharmacists, a happy team and relationships with other health professionals. CONCLUSION: This study described the distribution, roles and factors affecting rural and remote pharmacy practice. While the results presented provide an extensive overview of the rural/remote workforce, a comparable national study comparing rural/remote and urban pharmacists would further contribute to this discussion. Knowledge on why pharmacists chose to work in a particular geographical location, or why pharmacists chose to leave a location would further enrich our knowledge on what drives and sustains the rural/remote pharmacist workforce.

Exploring the appropriateness of prescribing practice of inhaled pharmacotherapy among Aboriginal Australians in the Top End Northern Territory of Australia: a retrospective cohort study.

BACKGROUND: Aboriginal Australians are reported to have a high burden of chronic airway diseases. However, prescribing patterns and related outcomes of airway directed inhaled pharmacotherapy, (short-acting beta agonists (SABA), short-acting muscarinic antagonists (SAMA), long-acting ß-agonists (LABA), long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)) among Aboriginal Australian patients with chronic airway disease have been sparsely reported in the past. METHODS: A retrospective cohort study was conducted, using clinical, spirometry data, chest radiology, primary healthcare (PHC) presentations and hospital admission rates among Aboriginal patients identified to have been prescribed inhaled pharmacotherapy in remote and rural communities referred to the respiratory specialist service in the Top End, Northern Territory of Australia. RESULTS: Of the 372 identified active patients, 346 (93%) had inhaled pharmacotherapy prescribed (64% female, median age 57.7 years). ICS was the most common prescription (72% of the total cohort) and was recorded to be prescribed in 76% of patients with bronchiectasis, and 80% of patients with asthma or chronic obstructive pulmonary disease (COPD). Fifty-eight percent of patients had a respiratory hospital admission and 57% had a recorded PHC presentation for a respiratory issue during the study period, with a higher rate of hospital admissions among patients prescribed ICS compared with those on SAMA/SABA or LAMA/LABA without ICS (median rate (per person per year) 0.42 vs 0.21 and 0.21 (p=0.004). Regression models demonstrated that presence of COPD or bronchiectasis alongside ICS was associated with significantly increased hospitalisation rates (1.01 admissions/person/year (95% CI 0.15 to 1.87) and 0.71 admissions/person/year (95% CI 0.23 to 1.18) against patients without COPD/bronchiectasis, respectively). CONCLUSIONS: This study demonstrates that among Aboriginal patients with chronic airway diseases, ICS is the most common inhaled pharmacotherapy prescribed. Although LAMA/LABA and concurrent ICS use may be appropriate among patients with asthma and COPD, the use of ICS may have detrimental effects among those with underlying bronchiectasis either in isolation or concurrent COPD and bronchiectasis, potentially leading to higher hospital admission rates.

Opportunities for clinical decision support targeting medication safety in remote primary care management of chronic kidney disease: A qualitative study in Northern Australia.

INTRODUCTION: This study aimed to identify opportunities for clinical decision support targeting medication safety in remote primary care, by investigating the relationship between clinical workflows, health system priorities, cognitive tasks, and reasoning processes in the context of medicines used in people with chronic kidney disease (CKD). METHODS: This qualitative study involved one-on-one, semistructured interviews. The participants were healthcare professionals employed in a clinical or managerial capacity with clinical work experience in a remote health setting for at least 1 year. RESULTS: Twenty-five clinicians were interviewed. Of these, four were rural medical practitioners, nine were remote area nurses, eight were Aboriginal health practitioners, and four were pharmacists. Four major themes were identified from the interviews: (1) the need for a clinical decision support system to support a sustainable remote health workforce, as clinicians were "constantly stretched" and problems may "fall through the cracks"; (2) reliance on digital health technologies, as medical staff are often not physically available and clinicians-on-duty usually "flick an email and give a call so that I can actually talk it through to our GP"; (3) knowledge gaps, as "it takes a lot of mental space" to know each patient's renal function and their medication history, and clinicians believe "mistakes can be made"; and (4) multiple risk factors impacting CKD management, including clinical, social and behavioural determinants. CONCLUSIONS: The high prevalence of CKD and reliance on digital health systems in remote primary health settings can make a clinical decision support system valuable for supporting clinicians who may not have extensive experience in managing medicines for people with CKD.

Investigation of a Multistate Outbreak of Listeria monocytogenes Infections Linked to Frozen Vegetables Produced at Individually Quick-Frozen Vegetable Manufacturing Facilities.

In 2016, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state partners investigated nine Listeria monocytogenes infections linked to frozen vegetables. The investigation began with two environmental L. monocytogenes isolates recovered from Manufacturer A, primarily a processor of frozen onions, that were a match by whole genome sequencing (WGS) to eight clinical isolates and historical onion isolates with limited collection details. Epidemiologic information, product distribution, and laboratory evidence linked suspect food items, including products sourced from Manufacturer B, also a manufacturer of frozen vegetable/fruit products, with an additional illness. The environmental isolates were obtained during investigations at Manufacturers A and B. State and federal partners interviewed ill people, analyzed shopper card data, and collected household and retail samples. Nine ill persons between 2013 and 2016 were reported in four states. Of four ill people with information available, frozen vegetable consumption was reported by three, with shopper cards confirming purchases of Manufacturer B brands. Two identified outbreak strains of L. monocytogenes (Outbreak Strain 1 and Outbreak Strain 2) were a match to environmental isolates from Manufacturer A and/or isolates from frozen vegetables recovered from open and unopened product samples sourced from Manufacturer B; the investigation resulted in extensive voluntary recalls. The close genetic relationship between isolates helped investigators determine the source of the outbreak and take steps to protect public health. This is the first known multistate outbreak of listeriosis in the United States linked to frozen vegetables and highlights the significance of sampling and WGS analyses when there is limited epidemiologic information. Additionally, this investigation emphasizes the need for further research regarding food safety risks associated with frozen foods.

Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52-87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15-30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015-001,235-20NCT00123456.

Providing community-based health practitioners with timely and accurate discharge medicines information.

BACKGROUND: Accurate and timely medication information at the point of discharge is essential for continuity of care. There are scarce data on the clinical significance if poor quality medicines information is passed to the next episode of care. This study aimed to compare the number and clinical significance of medication errors and omission in discharge medicines information, and the timeliness of delivery of this information to community-based health practitioners, between the existing Hospital Discharge Summary (HDS) and a pharmacist prepared Medicines Information Transfer Fax (MITF). METHOD: The study used a sample of 80 hospital patients who were at high risk of medication misadventure, and who had a MITF completed in the study period June - October 2009 at a tertiary referral hospital. The medicines information in participating patients' MITFs was validated against their Discharge Prescriptions (DP). Medicines information in each patient's HDS was then compared with their validated MITF. An expert clinical panel reviewed identified medication errors and omissions to determine their clinical significance. The time between patient discharge and the dispatching of the MITF and the HDS to each patient's community-based practitioners was calculated from hospital records. RESULTS: DPs for 77 of the 80 patients were available for comparison with their MITFs. Medicines information in 71 (92%) of the MITFs matched that of the DP. Comparison of the HDS against the MITF revealed that no HDS was prepared for 16 (21%) patients. Of the remaining 61 patients; 33 (54%), had required medications omitted and 38 (62%) had medication errors in their HDS. The Clinical Panel rated the significance of errors or omissions for 70 patients (16 with no HDS prepared and 54 who's HDS was inconsistent with the validated MITF). In 17 patients the error or omission was rated as insignificant to minor; 23 minor to moderate; 24 moderate to major and 6 major to catastrophic. 28 (35%) patients had their HDS dispatched to their community-based practitioners within 48 hours post discharge compared to 80 (100%) of MITFs. CONCLUSION: The MITF is an effective approach for the timely delivery of accurate discharge medicines information to community-based practitioners responsible for the patient's ongoing care.

Test-retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease.

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter.Here we quantified test-retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).Test-retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM).We conclude that pCASL has high test-retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015).

Sex hormone control of left ventricular structure/function: mechanistic insights using echocardiography, expression, and DNA methylation analyses in adult mice.

Calcium flux into and out of the sarco(endo)plasmic reticulum is vitally important to cardiac function because the cycle of calcium entry and exit controls contraction and relaxation. Putative estrogen and androgen consensus binding sites near to a CpG island are present in the cardiac calsequestrin 2 (CSQ2) promoter. Cardiomyocytes express sex hormone receptors and respond to sex hormones. We hypothesized that sex hormones control CSQ2 expression in cardiomyocytes and so affect cardiac structure/function. Echocardiographic analysis of male and female C57bl6n mice identified thinner walled and lighter hearts in females and significant concentric remodeling after long-term gonadectomy. CSQ2 and sodium-calcium exchanger-1 (NCX1) expression was significantly increased in female compared with male hearts and decreased postovariectomy. NCX1, but not CSQ2, expression was increased postcastration. CSQ2 expression was reduced when H9c2 cells were cultured in hormone-deficient media; increased when estrogen receptor-α (ERα), estrogen receptor-ß (ERß), or androgen agonists were added; and increased in hearts from ERß-deficient mice. CSQ2 expression was reduced in mice fed a diet low in the methyl donor folic acid and in cells treated with 5-azadeoxycytidine suggesting an involvement of DNA methylation. DNA methylation in CpG in the CSQ2 CpG island was significantly different in males and females and was additionally changed postgonadectomy. Expression of DNA methyltransferases 1, 3a, and 3b was unchanged. These studies strongly link sex hormone-directed changes in CSQ2 expression to DNA methylation with changed expression correlated with altered left ventricular structure and function.