Evaluating remote facilitation intensity for multi-national translation of nurse-initiated stroke protocols (QASC Australasia): a protocol for a cluster randomised controlled trial.

BACKGROUND: Facilitated implementation of nurse-initiated protocols to manage fever, hyperglycaemia (sugar) and swallowing difficulties (FeSS Protocols) in 19 Australian stroke units resulted in reduced death and dependency for stroke patients. However, a significant gap remains in translating this evidence-based care bundle protocol into standard practice in Australia and New Zealand. Facilitation is a key component for increasing implementation. However, its contribution to evidence translation initiatives requires further investigation. We aim to evaluate two levels of intensity of external remote facilitation as part of a multifaceted intervention to improve FeSS Protocol uptake and quality of care for patients with stroke in Australian and New Zealand acute care hospitals. METHODS: A three-arm cluster randomised controlled trial with a process evaluation and economic evaluation. Australian and New Zealand hospitals with a stroke unit or service will be recruited and randomised in blocks of five to one of the three study arms-high- or low-intensity external remote facilitation or a no facilitation control group-in a 2:2:1 ratio. The multicomponent implementation strategy will incorporate implementation science frameworks (Theoretical Domains Framework, Capability, Opportunity, Motivation - Behaviour Model and the Consolidated Framework for Implementation Research) and include an online education package, audit and feedback reports, local clinical champions, barrier and enabler assessments, action plans, reminders and external remote facilitation. The primary outcome is implementation effectiveness using a composite measure comprising six monitoring and treatment elements of the FeSS Protocols. Secondary outcome measures are as follows: composite outcome of adherence to each of the combined monitoring and treatment elements for (i) fever (n=5); (ii) hyperglycaemia (n=6); and (iii) swallowing protocols (n=7); adherence to the individual elements that make up each of these protocols; comparison for composite outcomes between (i) metropolitan and rural/remote hospitals; and (ii) stroke units and stroke services. A process evaluation will examine contextual factors influencing intervention uptake. An economic evaluation will describe cost differences relative to each intervention and study outcomes. DISCUSSION: We will generate new evidence on the most effective facilitation intensity to support implementation of nurse-initiated stroke protocols nationwide, reducing geographical barriers for those in rural and remote areas. TRIAL REGISTRATION: ACTRN12622000028707. Registered 14 January, 2022.

Effect of lifestyle focused text messaging on risk factor modification in patients with diabetes and coronary heart disease: A sub-analysis of the TEXT ME study.

AIMS: There is potential to provide public health interventions through text messaging for patients with Type 2 diabetes mellitus (T2DM). Our objective was to ascertain if lifestyle focused text messaging addressing cardiovascular risk factors in patients with coronary heart disease (CHD) and T2DM, was more effective than usual care. METHODS: This is a secondary analysis of the TEXT ME study, a randomised clinical trial of a 6-month text messaging intervention in patients with coronary heart disease. The measured outcomes include cholesterol, blood pressure (BP), body mass index (BMI), HbA1c, waist/hip circumference and smoking status. Our objective was to ascertain if lifestyle focused text messaging in patients with T2DM was more effective than usual care, and to determine if the intervention was more effective in patients with T2DM compared to those without. RESULTS: 229 participants in the TEXT ME study had T2DM (32%), 111 participants in the intervention group and 118 in the control group. At 6 months, the mean difference in systolic BP was -7.6 mmHg (95%CI -11.8, -3.37, p = 0.0003) and diastolic BP -3.7 mmHg (95%CI -6.12, -1.24, p = 0.0032). The mean difference in low density lipoprotein in the intervention arm, compared to the control arm, was -0.05 mmol/L (95%CI -0.27, 0.18, p = 0.813), and in triglycerides was -0.29 mmol/L (95%CI -0.59, 0.01, p = 0.035) respectively. The mean difference in BMI was -0.89 kg/m2 (95%CI -2.74, 0.95, p < 0.0001) in the intervention group, waist circumference -3.98 cm (95%CI -8.57, 0.61, p < 0.0001) and hip circumference -3.26 cm (95%CI -7.67, 1.16, p = 0.0006). Intervention subjects with diabetes were less likely to be smokers at 6 months. The mean difference in HbA1c between the control and intervention group was not significant (p = 0.126). The intervention was as effective in patients with diabetes, compared to those without. CONCLUSION: Among patients with coronary heart disease with T2DM, lifestyle-focused text messaging resulted in significant risk factor reduction.

New insights into Brunner syndrome and potential for targeted therapy.

We report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein-truncating variant of monoamine oxidase A (MAOA) (p.S251KfsX2). Affected males had mild intellectual disability (ID), obsessive behaviour, limited friendships and were introverted and placid during clinical interview. The family disclosed episodic explosive aggression after a diagnosis was made. The second family had a missense variant in MAOA (p.R45W). Affected males had borderline-mild ID, attention deficit disorder and limited friendships. One had a history of explosive aggression in childhood and episodic symptoms of flushing, headaches and diarrhoea. Their carrier mother had normal intelligence but similar episodic symptoms. Characteristic biochemical abnormalities included high serum serotonin and urinary metanephrines and low urinary 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA). Symptomatic individuals in the second family had particularly high serotonin levels, and treatment with a serotonin reuptake inhibitor and dietary modification resulted in reversal of biochemical abnormalities, reduction of 'serotonergic' symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild ID with paroxysmal behavioural symptoms. It can be screened for with serum/urine metanephrine and serotonin measurement. Cautious treatment with a serotonin reuptake inhibitor, dietary modifications and avoidance of medications contraindicated in patients on monoamine oxidase inhibitors can improve symptoms.

Microalbuminuria is a predictor of adverse pregnancy outcomes including preeclampsia.

OBJECTIVES: Abnormal urinary protein loss is a marker associated with a diverse range of renal diseases including preeclampsia. Current measures of urine protein used in the diagnostic criteria for the diagnosis of preeclampsia includes urine protein:creatinine ratio and 24-h urine protein. However very little is known about the value of urine albumin:creatinine ratio (uACR) in pregnancy. In this study we examined the prognostic value of microalbuminuria detected antepartum to predict adverse pregnancy outcomes. DESIGN: This is a single-centre retrospective analysis of 84 pregnant women over the age of 16 attending a tertiary 'high-risk' pregnancy outpatient clinic between July 2010 and June 2013. Utilising medical records, antepartum peak uACR level and pregnancy maternal and fetal outcomes were recorded. FINDINGS: The primary outcome was a composite of poor maternal and fetal outcomes including preeclampsia, maternal death, eclampsia, stillbirth, neonatal death, IUGR, premature delivery and placental abruption. As the antepartum peak uACR level (in mg/mmol) increased from normoalbuminuria (uACR<3.5) to microalbuminuria (uACR 3.5-35) to macroalbuminuria (>35), the percentage of women with the primary composite outcome increased in a stepwise fashion (13.8% to 24.1% to 62.1% respectively, p<0.001). After adjusting for covariates including history of hypertension, chronic kidney disease and aspirin therapy during pregnancy, micro- and macroalbuminuria remained significant predictors of the primary outcome. CONCLUSIONS: We have shown that antepartum peak uACR is a useful simple marker to help predict adverse maternal and fetal outcomes. Further studies are required to utilise uACR as a prognostic tool in pregnancy before it can be applied in clinical practice.

GCK monogenic diabetes and gestational diabetes: possible diagnosis on clinical grounds.

AIM: To determine if the previously published clinical criteria for identifying glucokinase monogenic diabetes [GCK gene mutation in maturity-onset diabetes of the young (GCK-MODY)], an elevated antenatal fasting blood glucose of 5.5-8.0 mmol/l, an increment of < 4.6 mmol/l at 2 h in an oral glucose tolerance test and slim are applicable in a large multi-ethnic cohort of women with gestational diabetes. METHODS: We analysed de-identified data from all women with gestational diabetes, diagnosed using the Australasian Diabetes in Pregnancy Society (1998) Australian criteria at our institution between 1993 and 2013, making comparisons among those with complete antenatal data including: diagnostic oral glucose tolerance test results meeting the above criteria; pregestational BMI; birth outcomes; and postpartum oral glucose tolerance test data. We categorized these women into two groups: Group A1 had a BMI ≤ 21 kg/m(2) and Group A2 had a BMI > 21 kg/m(2) and < 25 kg/m(2). RESULTS: Of the 302 women meeting the study entry criteria, we had complete data including a postpartum oral glucose tolerance test result for 171 women: 54 in Group A1 and 117 in Group A2. Ethnicity was significantly different between the groups. The oral glucose tolerance test and postpartum HbA1c results identified few women ( < 14%) in Group A1 and Group A2 who still had 'possible GCK-MODY'. CONCLUSIONS: Our findings indicate that previously recommended clinical criteria for the identification of women likely to have GCK-MODY lack specificity in a cohort of women with multi-ethnic backgrounds. Using these criteria to select women for testing for GCK-MODY in pregnancy would therefore be costly and is likely to yield few women positive for this condition.

Gestational diabetes: a red flag for future Type 2 diabetes in pregnancy? A retrospective analysis.

AIMS: This study sought to understand the relationship between Type 2 diabetes in pregnancy and previous gestational diabetes (GDM), and determine whether a previous pregnancy with GDM was associated with subsequent better pregnancy planning. METHODS: A retrospective review of medical records of women with Type 2 diabetes in pregnancy was conducted at three teaching hospitals to ascertain whether they had earlier GDM, and to determine whether this is associated with differences in measures of pregnancy planning and diabetes management. RESULTS: Of 172 index pregnancies affected by Type 2 diabetes, in 76 (44%) cases, the mother had a previous history of GDM. Within this cohort, a diagnosis of 'overt diabetes in pregnancy', made on the basis of a GTT result during pregnancy in the WHO diabetic range with persistent diabetes post partum, was more common among women who had previous GDM than women who had not had GDM (20% vs 7%, P = 0.02). Women who previously had GDM did not exhibit a higher incidence of preconception planning or folate supplementation. CONCLUSIONS: It is common for women with Type 2 diabetes in pregnancy to have had GDM previously. The diagnosis of GDM is an opportunity to improve future pregnancy planning and outcomes for women with Type 2 diabetes in pregnancy. This goal is yet to be realized.

Beta-cell ARNT is required for normal glucose tolerance in murine pregnancy.

AIMS: Insulin secretion increases in normal pregnancy to meet increasing demands. Inability to increase beta-cell function results in gestational diabetes mellitus (GDM). We have previously shown that the expression of the transcription factor ARNT (Aryl-hydrocarbon Receptor Nuclear Translocator) is reduced in the islets of humans with type 2 diabetes. Mice with a beta-cell specific deletion of ARNT (ß-ARNT mice) have impaired glucose tolerance secondary to defective insulin secretion. We hypothesised that ARNT is required to increase beta-cell function during pregnancy, and that ß-ARNT mice would be unable to compensate for the beta-cell stress of pregnancy. The aims of this study were to investigate the mechanisms of ARNT regulation of beta-cell function and glucose tolerance in pregnancy. METHODS: ß-ARNT females were mated with floxed control (FC) males and FC females with ß-ARNT males. RESULTS: During pregnancy, ß-ARNT mice had a marked deterioration in glucose tolerance secondary to defective insulin secretion. There was impaired beta-cell proliferation in late pregnancy, associated with decreased protein and mRNA levels of the islet cell-cycle regulator cyclinD2. There was also reduced expression of Irs2 and G6PI. In contrast, in control mice, pregnancy was associated with a 2.1-fold increase in ARNT protein and a 1.6-fold increase in cyclinD2 protein, and with increased beta-cell proliferation. CONCLUSIONS: Islet ARNT increases in normal murine pregnancy and beta-cell ARNT is required for cyclinD2 induction and increased beta-cell proliferation in pregnancy.

Implementation of a dedicated hospital subcutaneous insulin prescription chart: effect on glycaemic control.

A dedicated subcutaneous insulin prescription chart incorporating glucose monitoring results, forced functions, and management guidelines was introduced to facilitate better hospital diabetes control. Point of care capillary blood glucose monitoring charts for 99 people with diabetes from the period before the introduction of the new chart, and 106 after its introduction were reviewed. A total of 12,649 blood glucose levels (BGLs) were collected for glucometric analysis. Following the introduction of the chart, there was an increase in the number of BGLs performed daily from 4.5 ± 1.2 to 4.9 ± 1.3 (p = 0.05). There was an increase in the proportion of BGLs within the ideal range of 4-9.9 mmol/L (51.8% vs. 54.1%, p = 0.01). There was a reduction in hypoglycaemic events (proportion of BGLs <4 mmol/L in the whole population decreased from 5.2% to 3.4% (p < 0.001), proportion of BGLs <4 mmol/L for each patient decreased from 5.6 ± 9.2% to 2.9 ± 5.4% (p = 0.01), proportion of days where patient had a BGL <4 mmol/L decreased from 17.6 ± 22.6% to 11.4 ± 18.8% (p = 0.03)), despite an increase in the use of supplemental insulin (14.2 ± 35.7 vs. 29.4 ± 51.4 u nits/patient, p = 0.02). We conclude that the use of a dedicated hospital subcutaneous insulin prescription chart can reduce hypoglycaemia and improve some measures of glycaemic control.

A pilot structured behavioural intervention trial to increase physical activity among women with recent gestational diabetes.

Forty-three women were recruited into a 1-year randomised controlled trial to test the feasibility of a structured behavioural intervention to increase physical activity after gestational diabetes. Increases in achievement of physical activity targets were not attained. Recruitment and subject retention were identified as major challenges.

Synergistic effects of genetic beta cell dysfunction and maternal glucose intolerance on offspring metabolic phenotype in mice.

AIMS/HYPOTHESIS: Diabetes in pregnancy is linked to development of obesity in the offspring, but the mechanisms are not fully understood. Gestational diabetes mellitus (GDM) occurs when beta cells are unable to compensate for the normal insulin resistance of late pregnancy. In this study, we used a murine model of beta cell dysfunction to examine the effects of maternal GDM on phenotype in male offspring with and without an inherited predisposition for beta cell dysfunction. METHODS: Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null (ßArnt) mice develop GDM from beta cell dysfunction. ßArnt and control female mice were used to induce GDM and non-diabetic pregnancies, respectively. RESULTS: Offspring from GDM pregnancies became spontaneously obese on a normal-chow diet. They were heavier than offspring from non-diabetic pregnancies, with increased body fat. Respiratory exchange ratio (RER) was higher, indicating decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring was decreased prior to onset of obesity. The phenotype was more pronounced in ßArnt GDM offspring than in GDM offspring of control genotype, demonstrating an interaction between genotype and pregnancy exposure. ßArnt GDM offspring had increased hypothalamic neuropeptide Y (Npy) and decreased pro-opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER in all mice, and hypothalamic Npy in ßArnt mice were significantly correlated with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia. CONCLUSIONS/INTERPRETATION: In ßArnt mice, exposure to GDM and inheritance of genetic beta cell dysfunction had additive effects on male offspring obesity; severity of the offspring phenotype correlated with maternal glycaemia.

Sliding scale insulin: will the false idol finally fall?

Despite a lack of evidence that sliding scale insulin has any clinical benefit, and some evidence that it may even be detrimental, sliding scale insulin is still commonly prescribed in hospitals today. Adopting a proactive rather than a reactive approach to managing diabetes by the use of 'supplemental insulin', given in conjunction with either considered adjustments to the patient's regular anti-diabetic therapy or the provision of basal insulin, is a more effective and safer means of improving glycaemic control in hospital. There are now randomized trial data to support this approach. These data, together with the recognition that there is no evidence base for the use of sliding scale insulin, coupled with changes to insulin prescribing charts in Australia, should lead to the demise of sliding scale insulin use in hospital.

Effect of insulin infusion on electrocardiographic findings following acute myocardial infarction: importance of glycaemic control.

AIMS: To determine the effects of insulin infusion and blood glucose levels during acute myocardial infarction (AMI) on electrocardiographic (ECG) features of myocardial electrical activity. METHODS: ECGs at admission and 24 h were examined in a randomized study of insulin infusion vs. routine care for AMI patients with diabetes or hyperglycaemia. Results were analysed according to treatment allocation and also according to average blood glucose level. RESULTS: ECG characteristics were similar at admission in both groups. Patients allocated to conventional treatment had prolongation of the QT interval (QTc) after 24 h but those receiving infused insulin did not. In patients with a mean blood glucose in the first 24 h > 8.0 mmol/l, new ECG conduction abnormalities were significantly more common than in patients with mean blood glucose

A pilot randomised controlled trial of resistance exercise bands in the management of sedentary subjects with type 2 diabetes.

We conducted a 4-month randomised controlled trial of home-based resistance training using exercise bands, amongst people with type 2 diabetes and co-morbidities limiting aerobic exercise capacity. The intervention did not improve HbA1c, anthropometric variables or functional capacity. We conclude that short-term use of exercise bands does not improve glycaemic control.

A comparison of diabetes clinics with different emphasis on routine care, complications assessment and shared care.

OBJECTIVE: To compare clinical outcomes of patients attending diabetes clinics with different models of care. METHODS: Diabetes centres which participated in the Australian National Diabetes Information Audit and Benchmarking (ANDIAB) data collection were invited to nominate whether they provided (i) routine diabetes care only (model A), (ii) routine care and structured annual complications screening (model B) or (iii) annual review and complications screening in a system of shared care with general practitioners (model C). De-identified case data were extracted from ANDIAB and outcomes according to the three clinic models were compared. RESULTS: Data on 3052 patients from 18 diabetes centres were analysed. Centres which practised annual complications screening (models B and C) had higher rates of nephropathy and lipid screening and a higher rate of attainment of recommended blood pressure and glycated haemoglobin (HbA(1c)) targets. The implementation of appropriate treatment for patients who had not attained the targets was similar for all three clinic models. CONCLUSIONS: In our study, clinic models which incorporate a system of structured complications screening were more likely to have met screening guidelines. Patients in a shared-care model were at least as likely to have met management targets as those attending diabetes clinics for their routine care. Therefore, a system of shared care by general practitioners supported by annual review at a diabetes clinic may be an acceptable model which improves the capacity to manage large numbers of people with diabetes, without loss of quality of care.

Glucose control during acute myocardial infarction.

The need for tight glycaemic control in the immediate aftermath of myocardial infarction is controversial. Trials of glucose-insulin-potassium (GIK) therapy, given without regard to glucose levels, have only confused the issue. Despite considerable clinical interest, only three randomized controlled trials have, as their primary goal, aimed to determine whether better glycaemic control improves the outcomes of myocardial infarction. This review examines the results of these trials and other data to support the case for tight glycaemic control in patients with myocardial infarction.

The relationship between admission blood glucose levels and hospital mortality.

AIMS/HYPOTHESIS: The purpose of this study was to examine the relationship between blood glucose level (BGL) on admission with mortality rates among patients admitted to hospital through the Emergency Department. METHODS: In a prospective observational study, BGLs were routinely measured on 6,187 consecutive patients requiring blood testing and admitted through the Emergency Department of a tertiary referral hospital. These measurements were matched against demographic data and hospital mortality rates. RESULTS: Overall in-hospital mortality was 4.8%. Admission BGL was an independent predictor of mortality (HR 1.04 per 1 mmol/l increase, 95% CI 1.02-1.06, p=0.02). There was a significant interaction between diabetes status and increasing BGL on mortality (p<0.001), with higher BGLs being associated with greater mortality among non-diabetic than among diabetic patients. Among non-diabetic patients, the lowest mortality rate (3.0%) was in people with a BGL of 4.0-5.9 mmol/l. Compared with this group, patients with a BGL of 8.0-9.9 mmol/l had increased mortality rate (7.6%, HR 1.56, 95% CI 1.03-2.35, p=0.04, after adjustment for age and sex). The risk increased further at higher glucose levels. In the cohort with diagnosed diabetes, the increase in mortality rates at higher BGL bands was not significant. CONCLUSIONS/INTERPRETATION: Among people who do not have diabetes, even modest degrees of hyperglycaemia on hospital admission are associated with increased mortality.

What glucose target should we aim for in myocardial infarction?

Hyperglycaemia in the period following myocardial infarction is associated with increased mortality and there is some evidence that its treatment can improve survival. However, it remains unclear as to what the ideal glucose targets might be. This study examined observational data taken from a previously reported randomised controlled trial of insulin therapy for myocardial infarction (The Hyperglycaemia: Intensive Insulin Infusion In Infarction Study), to determine optimal glucose levels for this period. Capillary glucose readings were recorded at 8 standard time points for 234 subjects in first 24h after myocardial infarction. Survival over 6 months was analysed according to whether 80% of each subject's glucose readings were below specified glucose thresholds (Achievers) or not (Non-Achievers). We found that the glucose threshold at which there was greatest separation in mortality between Achievers and Non-Achievers was at 8mmol/L [144mg/dL] (6 month mortality 1.6% vs. 9.1%, p=0.05). Therefore subjects who maintained the majority of their blood glucose levels below 8mmol/L following myocardial infarction had optimal survival outcomes. We suggest that this might be an appropriate glucose target to aim for in the peri-infarct period.

Comparison of international and New Zealand guidelines for the care of pregnant women with diabetes.

OBJECTIVE: To compare international guidelines for the care of women with diabetes and pregnancy with reported current practice among New Zealand tertiary centres. RESEARCH DESIGN AND METHODS: A literature review of national and international guidelines for the care of women with diabetes in pregnancy was undertaken. Guideline activities were placed within nine facets of care, from preconception advice, through pregnancy from screening to follow-up. New Zealand tertiary centres guidelines were obtained and placed in the same framework. RESULTS: International guideline consensus was inconsistent across most facets of care. Those for the detection and diagnosis of gestational diabetes mellitus (GDM) were particularly discordant internationally, although intranational agreement has occurred. CONCLUSIONS: International guidelines for the care of women with diabetes in pregnancy remain fragmented. The development of one set of guidelines based on the consensus of international best practice could overcome many of the misconceptions associated with diabetes in pregnancy.

Is parity associated with earlier diagnosis of type 2 diabetes?

AIM: Whether parity promotes the development of diabetes has been a subject of controversy. Earlier population studies have produced discrepant findings. The aim of the current study was to investigate this question by examining the relationship between parity and the age of diagnosis of diabetes. METHODS: A retrospective analysis from a diabetes database was conducted. Data for 2102 women with type 2 diabetes (T2DM), including date of birth, age at diagnosis, parity, body mass index (BMI), and family history were extracted. A multivariate linear regression model was applied to ascertain if there was an association between parity and the age of diagnosis of diabetes. RESULTS: With correction for the year of birth, there was a significant association between parity and the age of diagnosis of diabetes (beta = -0.25 +/- 0.08, P = 0.002, where beta is the regression coefficient). That is, for an increase in parity by one, the age of diagnosis decreased by 0.25 years. When further adjustments were made for the other variables in the data set, the effect on the overall cohort disappeared, but it persisted in subjects born before 1950 (beta = -0.17 +/- 0.1, P = 0.09), or with a parity >5 (beta = -0.60 +/- 0.25, P = 0.02). CONCLUSIONS: There is an association between parity and the age of diagnosis of diabetes, suggesting that pregnancy may promote the development of diabetes. However, the magnitude of the effect is small, and unlikely to be of great clinical significance in society today.