Antenatal health and perinatal outcomes of Pacific Islander women in Australia with and without gestational diabetes: A ten-year retrospective cohort study.

BACKGROUND: Pacific Islander (PI) women in Australia have an increased risk of gestational diabetes (GDM); however, their perinatal outcomes are poorly understood. AIM: The aim was to determine the maternal characteristics and perinatal outcomes of PI women with and without GDM compared to Australian/European (AE)-born women. METHODS: A retrospective analysis of perinatal outcomes of singleton deliveries >20 weeks' gestation between 1 January 2011 and 31 December 2020 was conducted at a tertiary provider (Melbourne, Australia). Antenatal details and birth outcomes were extracted from the Birth Outcome Systems database. t-Tests and χ2, univariate and multivariable logistic regression analyses assessed the relationship between ethnicity and outcomes. RESULTS: Of 52,795 consecutive births, 24,860 AE women (13.3% with GDM) and 1207 PI-born women (20.1% with GDM) were compared. PI women had significantly greater pre-pregnancy body mass index (BMI) and significantly lower rates of smoking and nulliparity. PI women with GDM had higher rates of pre-eclampsia (P < 0.001), large-for-gestational age (LGA) neonates (P = 0.037) and neonatal hypoglycaemia (P = 0.017) but lower rates of small-for-gestational age neonates (P = 0.034). Neonatal intensive care unit (NICU)/special care nursery requirements did not increase. After having adjusted for covariates, PI women's risk of LGA neonates (adjusted odds ratio (aOR): 1.06, 95% confidence interval (CI): 0.86-1.31) was attenuated; however, risk of pre-eclampsia (aOR: 1.49, 95% CI: 1.01-2.21) and neonatal hypoglycaemia (aOR: 1.40, 95% CI: 1.01-1.96) still increased. They were less likely to require a primary caesarean section (aOR: 0.86, 95% CI: 0.73-0.99). CONCLUSION: PI women have higher BMI and GDM rates, contributing to an increased likelihood of adverse perinatal outcomes. BMI is a modifiable risk factor that could be addressed prenatally.

Case report of the successful use of semaglutide to achieve target BMI prior to renal transplant in two patients with end-stage-kidney-disease.

The following cases demonstrate a proof of concept for the safe and effective use of the glucagon-like-peptide-1 receptor agonist (GLP-1 RA) semaglutide for weight loss in obese, non-diabetic, end stage kidney disease (ESKD) patients on haemodialysis (HD), who are unable to undergo renal transplantation due to obesity. Obesity is a common barrier to wait-listing for renal transplantation with effective, broadly applicable weight loss strategies lacking. GLP-1 RAs have been shown to be effective adjuncts to achieve weight loss in non-diabetic obese people. However, the major clinical trials excluded patients with ESKD on dialysis. This paper outlines the successful use of semaglutide to achieve a target body mass index (BMI) prior to renal transplant wait-listing in two obese, non-diabetic, HD patients. These patients achieved a 16% and 12.6% weight loss in under 9 months with one now waitlisted and the other transplanted. This strategy has the potential for broader use in this patient cohort to improve wait-list times by overcoming this common barrier to renal transplantation.

Chronic disease IMPACT (chronic disease early detection and improved management in primary care project): An Australian stepped wedge cluster randomised trial.

Background: Interrelated chronic vascular diseases (chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease (CVD)) are common with high morbidity and mortality. This study aimed to assess if an electronic-technology-based quality improvement intervention in primary care could improve detection and management of people with and at risk of these diseases. Methods: Stepped-wedge trial with practices randomised to commence intervention in one of five 16-week periods. Intervention included (1) electronic-technology tool extracting data from general practice electronic medical records and generating graphs and lists for audit; (2) education regarding chronic disease and the electronic-technology tool; (3) assistance with quality improvement audit plan development, benchmarking, monitoring and support. De-identified data analysis using R 3.5.1 conducted using Bayesian generalised linear mixed model with practice and time-specific random intercepts. Results: At baseline, eight included practices had 37,946 active patients (attending practice ≥3 times within 2 years) aged ≥18 years. Intervention was associated with increased OR (95% CI) for: kidney health checks (estimated glomerular filtration rate, urine albumin:creatinine ratio (uACR) and blood pressure) in those at risk 1.34 (1.26-1.42); coded diagnosis of CKD 1.18 (1.09-1.27); T2D diagnostic testing (fasting glucose or HbA1c) in those at risk 1.15 (1.08-1.23); uACR in patients with T2D 1.78 (1.56-2.05). Documented eye checks within recommended frequency in patients with T2D decreased 0.85 (0.77-0.96). There were no significant changes in other assessed variables. Conclusions: This electronic-technology-based intervention in primary care has potential to help translate guidelines into practice but requires further refining to achieve widespread improvements across the interrelated chronic vascular diseases.

Participants' and Health Care Providers' Insights Regarding a Web-Based and Mobile-Delivered Healthy Eating Program for Disadvantaged People With Type 2 Diabetes: Descriptive Qualitative Study.

BACKGROUND: Healthy eating is a key element of type 2 diabetes (T2D) self-management. Digital interventions offer new avenues to reach broad audiences to promote healthy eating behaviors. However, acceptance of these interventions by socioeconomically disadvantaged people (eg, those with lower levels of education and income or from ethnic minority groups) has not yet been fully evaluated. OBJECTIVE: This study aimed to investigate the acceptability and usability of EatSmart, a 12-week web-based and mobile-delivered healthy eating behavior change support program, from the perspective of intervention participants living with T2D and health care providers (HCPs) involved in diabetes care. METHODS: This study used a qualitative descriptive design. Overall, 60 disadvantaged adults with T2D, as determined by receipt of either a HealthCare Card or a pension or benefit as the main source of income, were recruited. Data from participants regarding their experiences with and perceptions of the program and longer-term maintenance of any behavior or attitudinal changes were collected through a web-based self-report survey with open-ended questions administered 12 weeks after baseline (54/60, 90%) and semistructured telephone interviews administered 36 weeks after baseline (16/60, 27%). Supplementary semistructured interviews with 6 HCPs involved in diabetes care (endocrinologists, accredited practicing dietitians, and diabetes nurse educators) were also conducted 36 weeks after baseline. These interviews aimed to understand HCPs' views on successful and unsuccessful elements of EatSmart as a technology-delivered intervention; any concerns or barriers regarding the use of these types of interventions; and feedback from their interactions with patients on the intervention's content, impact, or observed benefits. All data from the surveys and interviews were pooled and thematically analyzed. RESULTS: In total, 5 key themes emerged from the data: program impact on food-related behaviors and routines, satisfaction with the program, reasons for low engagement and suggestions for future programs, benefits and challenges of digital interventions, and cultural considerations. Results showed that EatSmart was acceptable to participants and contributed positively to improving food-related behaviors. Most participants (27/43, 63%) mentioned that they enjoyed their experience with EatSmart and expressed high satisfaction with its content and delivery. The educational and motivational content was considered the most useful part of the program. Benefits discussed by intervention participants included gaining health knowledge and skills, positive changes in their food purchasing and cooking, and eating greater quantities and varieties of fruits and vegetables. HCPs also described the intervention as beneficial and persuasive for the target audience and had specific suggestions for future tailoring of such programs. CONCLUSIONS: The findings suggested that this digitally delivered intervention with supportive educational modules and SMS text messages was generally appealing for both participants and HCPs. This intervention medium shows promise and could feasibly be rolled out on a broader scale to augment usual diabetes care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19488.

Using electronic medical record data to assess chronic kidney disease, type 2 diabetes and cardiovascular disease testing, recognition and management as documented in Australian general practice: a cross-sectional analysis.

OBJECTIVES: To evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases-chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease. DESIGN: Cross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population. SETTING: Eight GPs in Victoria, Australia. PARTICIPANTS: Patients were ≥18 years and attended GP ≥3 times within 24 months. 37 946 patients were included. RESULTS: Risk factor and disease testing/monitoring/treatment were assessed as per Australian guidelines (or US guidelines if none available), with guidelines simplified due to limitations in data availability where required. Risk factor assessment in those requiring it: 30% of patients had body mass index and 46% blood pressure within guideline recommended timeframes. Diagnostic testing in at-risk population: 17% had diagnostic testing as per recommendations for CKD and 37% for T2D. Possible undiagnosed disease: Pathology tests indicating possible disease with no diagnosis already coded were present in 6.7% for CKD, 1.6% for T2D and 0.33% familial hypercholesterolaemia. Overall prevalence: Coded diagnoses were recorded in 3.8% for CKD, 6.6% for T2D, 4.2% for ischaemic heart disease, 1% for heart failure, 1.7% for ischaemic stroke, 0.46% for peripheral vascular disease, 0.06% for familial hypercholesterolaemia and 2% for atrial fibrillation. Pharmaceutical prescriptions: the proportion of patients prescribed guideline-recommended medications ranged from 44% (beta blockers for patients with ischaemic heart disease) to 78% (antiplatelets or anticoagulants for patients with ischaemic stroke). CONCLUSIONS: Using GP EMR data, this study identified recorded diagnoses of chronic vascular diseases generally similar to, or higher than, reported national prevalence. It suggested low levels of extractable documented risk factor assessments, diagnostic testing in those at risk and prescription of guideline-recommended pharmacotherapy for some conditions. These baseline data highlight the utility of GP EMR data for potential use in epidemiological studies and by individual practices to guide targeted quality improvement. It also highlighted some of the challenges of using GP EMR data.

Prolactin ordering patterns in psychiatric inpatients and the impact this has on patient management.

OBJECTIVE: Guidelines stipulate that baseline prolactin be ordered prior to commencing antipsychotic treatment to facilitate investigation of any subsequent hyperprolactinaemic symptoms. The aim was to observe when and why prolactin levels are ordered for psychiatry inpatients commencing or continuing antipsychotics and how this alters clinical management. METHODS: Psychiatry inpatients admitted to the Alfred Hospital, Melbourne, Australia, in 2018 with the diagnoses of psychosis, schizophrenia, schizo-affective disorder or bipolar affective disorder were retrospectively analysed. Results and clinical history data were collected in patients in whom prolactin was ordered during or within 12 months of the relevant admission. RESULTS: Of 592 patients admitted during this period, 90 had prolactin ordered. Eight (8.9%) of the 90 tests were for hyperprolactinaemic symptoms, while the remainder were routine blood work. The results altered clinical management in 10 of the 90 (11.1%) patients. Of these 10, 8 were symptomatic. In the six patients with first episode psychosis, only one had prolactin ordered prior to antipsychotic commencement. CONCLUSIONS: Adherence to guideline recommendations of baseline prolactin testing was poor. When established on antipsychotics, measuring prolactin rarely changed management in asymptomatic patients; however, it did in those with hyperprolactinaemic symptoms. Measuring prolactin in asymptomatic patients on antipsychotics appears unhelpful.

EatSmart, a Web-Based and Mobile Healthy Eating Intervention for Disadvantaged People With Type 2 Diabetes: Protocol for a Pilot Mixed Methods Intervention Study.

BACKGROUND: People of low socioeconomic position (SEP) are disproportionately affected by type 2 diabetes (T2D), partly due to unhealthy eating patterns that contribute to inadequate disease self-management and prognosis. Digital technologies have the potential to provide a suitable medium to facilitate diabetes education, support self-management, and address some of the barriers to healthy eating, such as lack of nutritional knowledge or shopping or cooking skills, in this target group. OBJECTIVE: This study aims to test the feasibility, appeal, and potential effectiveness of EatSmart, a 12-week, evidence-based, theoretically grounded, fully automated web-based and mobile-delivered healthy eating behavior change program to help disadvantaged people living with T2D to eat healthily on a budget and improve diabetes self-management. METHODS: EatSmart is a mixed methods (quantitative and qualitative) pre-post design pilot study. Sixty socioeconomically disadvantaged people with T2D aged 18 to 75 years will be recruited. Participants will complete self-reported baseline assessments of their basic demographic and clinical data, dietary intake, dietary self-efficacy, and barriers to healthy eating. They will be provided with login access to the EatSmart web program, which includes six progressive skill-based modules covering healthy eating planning; smart food budgeting and shopping; time-saving meal strategies, healthy cooking methods, modifying recipes; and a final reinforcement and summary module. Over the 3-month intervention, participants will also receive 3 text messages weekly, encouraging them to review goals, continue to engage with different components of the EatSmart web program, and eat healthily. Participants will undertake follow-up assessments directly following the intervention 3 months post baseline and again after a 6-month postintervention follow-up period (9 months post baseline). Feasibility will be evaluated using the number of participants recruited and retained and objective indicators of engagement with the website. Program appeal and potential effects on primary and secondary outcomes will be assessed via the same surveys used at baseline, with additional questions asking about experience with and perceptions of the program. In-depth qualitative interviews will also be conducted 6 months post intervention to provide deeper insight into experiences with EatSmart and a more comprehensive description of the program's appeal. RESULTS: The EatSmart website has been developed, and all participants have viewed the modules as of May 2020. Results are expected to be submitted for publication in December 2020. CONCLUSIONS: This study will provide data to address the currently limited evidence regarding whether disadvantaged populations with T2D may benefit from digitally delivered behavior change programs that facilitate eating healthily on a budget. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001111167; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619001111167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19488.

Evolving Evidence of Diabetic Ketoacidosis in Patients Taking Sodium-Glucose Cotransporter 2 Inhibitors.

INTRODUCTION: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as an important class of blood glucose-lowering medications, due to cardiovascular, metabolic, and renal benefits. However, there is a small but significant risk of diabetic ketoacidosis (DKA) associated with their use. METHODS: A literature search was conducted in Ovid MEDLINE and Embase to July 2019 using variants on the key search terms sodium-glucose cotransporter 2, diabetic ketoacidosis, and type 2 diabetes. A broad spectrum of evidence was incorporated to facilitate a comprehensive narrative review. Further sources were identified through hand searching of reference lists. DISCUSSION: Although cardiovascular outcome trials demonstrated mixed evidence of SGLT2i associated DKA, increasing evidence from case reports and cohort studies has identified an increased risk. SGLT2i use is associated with a ketotic state caused by an increased glucagon:insulin ratio and stimulated by factors including stress-induced hormonal changes, insufficient insulin, decreased glucose, increased ketone resorption, and hypovolemia. Atypical presentations of DKA with lower-than-expected blood glucose levels are possible with SGLT2i use, so clinical and biochemical monitoring is vital for early identification and management. DKA risk is particularly increased with precipitating factors, therefore optimization of risk factors is vital. Recommendations for perioperative and sick day management of patients taking SGLT2i have been suggested based on available evidence. CONCLUSION: SGLT2i are an excellent class of drug in the physician's toolkit for managing type 2 diabetes. However, both clinicians and patients must be aware of the potential for DKA and the need for increased monitoring, both clinically and biochemically, when potential precipitating factors are present. In acutely unwell patients, these medications should be withheld to reduce the risk of DKA.

Successful medical management of insulinoma with diazoxide for 27 years.

SUMMARY: Despite improvements in localisation techniques and surgical advances, some patients with insulinoma will not be cured by surgery or may not be suitable for surgery. Medical management with diazoxide is an option for such cases. This case report details 27 years of successful management of insulinoma using diazoxide. It has been effective and safe, with only minor adverse effects. LEARNING POINTS: Long term diazoxide use can be a safe, effective option for insulinoma when it cannot be localised or removed surgically. Common adverse effects include peripheral oedema, hyperuricaemia, and hirsutism. 68Ga-NOTA-exendin-4 PET/CT scan should be considered for insulinoma localisation when other modalities have been unhelpful.

A physician-initiated double-blind, randomised, placebo-controlled, phase 2 study evaluating the efficacy and safety of inhibition of NADPH oxidase with the first-in-class Nox-1/4 inhibitor, GKT137831, in adults with type 1 diabetes and persistently elevated urinary albumin excretion: Protocol and statistical considerations.

PURPOSE: Kidney disease caused by type 1 diabetes can progress to end stage renal disease and can increase mortality risk. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) plays a major role in producing oxidative stress in the kidney in diabetes, and its activity is attenuated by GKT137831, an oral Nox inhibitor with predominant inhibitory action on Nox-1 and Nox - 4. Previous studies have demonstrated renoprotective effects with GKT137831 in various experimental models of type 1 diabetes-related kidney disease. This study will evaluate the effect of GKT137831 in treating clinical diabetic kidney disease. DESIGN: This is a multi-center, randomized, placebo-controlled trial, parallel arm study evaluating the effect on albuminuria of treatment with GKT137831 400 mg BID for 48 weeks. The study will randomize 142 participants who have persistent albuminuria and estimated glomerular filtration rate (eGFR) at baseline of at least 40 ml/min/1.73m2. PRIMARY OUTCOME MEASURES: Difference between arms in urine albumin to creatinine ratio. Secondary outcome measures include eGFR. CONCLUSION: This study is important because it may identify a new way of slowing renal disease progression in people with type 1 diabetes and albuminuria already receiving standard of care treatment.

Pooled genome wide association detects association upstream of FCRL3 with Graves' disease.

BACKGROUND: Graves' disease is an autoimmune thyroid disease of complex inheritance. Multiple genetic susceptibility loci are thought to be involved in Graves' disease and it is therefore likely that these can be identified by genome wide association studies. This study aimed to determine if a genome wide association study, using a pooling methodology, could detect genomic loci associated with Graves' disease. RESULTS: Nineteen of the top ranking single nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056 reaching genome wide significance (p = 5 × 10-8). Technical validation of top ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with individual genotyping in the discovery cohort revealed four single nucleotide polymorphisms with p ≤ 10-4. Rs17676303 on chromosome 1q23.1, located upstream of FCRL3, showed evidence of association with Graves' disease across the discovery, replication and combined cohorts. A second single nucleotide polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association supported by finding in the replication cohort that warrants further study. CONCLUSIONS: Pooled genome wide association study identified a genetic variant upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to those identified in the Major Histo-compatibility Complex. A second locus downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease that requires further confirmation.

Persistent syndrome of inappropriate antidiuretic hormone secretion following traumatic brain injury.

UNLABELLED: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case reports describing chronic SIADH and all resolved within 12 months, except for one case complicated by meningo-encephalitis. Persistent symptomatic hyponatremia due to chronic SIADH was present for 4 years following a TBI in a previously well 32-year-old man. Hyponatremia consistent with SIADH initially occurred in the immediate period following a high-speed motorbike accident in 2010. There were associated complications of post-traumatic amnesia and mild cognitive deficits. Normalization of serum sodium was achieved initially with fluid restriction. However, this was not sustained and he subsequently required a permanent 1.2 l restriction to maintain near normal sodium levels. Multiple episodes of acute symptomatic hyponatremia requiring hospitalization occurred over the following years when he repeatedly stopped the fluid restriction. Given the ongoing nature of his hyponatremia and difficulties complying with strict fluid restriction, demeclocycline was commenced in 2014. Normal sodium levels without fluid restriction have been maintained for 6 months since starting demeclocycline. This case illustrates an important long-term effect of TBI, the challenges of complying with permanent fluid restrictions and the potential role of demeclocycline in patients with chronic hyponatremia due to SIADH. LEARNING POINTS: Hyponatraemia due to SIADH commonly occurs after TBI, but is usually mild and transient.Chronic hyponatraemia due to SIADH following TBI is a rare but important complication.It likely results from damage to the pituitary stalk or posterior pituitary causing inappropriate non-osmotic hypersecretion of ADH.First line management of SIADH is generally fluid restriction, but hypertonic saline may be required in severe cases. Adherence to long-term fluid restriction is challenging. Other options include oral urea, vasopressin receptor antagonists and demeclocycline.While effective, oral urea is poorly tolerated and vasopressin receptor antagonists are currently not licensed for use in Australia or the USA beyond 30 days due to insufficient long-term safety data and specific concerns of hepatotoxicity.Demeclocycline is an effective, well-tolerated and safe option for management of chronic hyponatraemia due to SIADH.