A codesigned integrated kidney and diabetes model of care improves patient activation among patients from culturally and linguistically diverse backgrounds.

BACKGROUND: Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD. METHODS: This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non-CALD backgrounds spoke English only as their primary language. Paired t-tests compared baseline and 12-month patient activation scores by CALD status. RESULTS: Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non-CALD backgrounds (58.5 ± 14.6) at baseline. Within-group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow-up (52.1 ± 17.6-59.4 ± 14.7), and no significant change was observed for those from non-CALD backgrounds (58.5 ± 14.6-58.8 ± 13.6). CONCLUSIONS: Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi-structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses.

Improving women's experiences with gestational diabetes from culturally and linguistically diverse backgrounds in Australia: a qualitative study.

Introduction: Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in many countries worldwide, including Australia. Although studies have explored the experiences of women with GDM from ethnic minority groups, few have compared their experiences with women from Anglosphere backgrounds. Objective: To investigate the responses to diagnosis, the management of GDM, and the experiences of healthcare services among women with GDM from different culturally and linguistically diverse (CALD) backgrounds. Methods: Participants were recruited via convenience sampling by advertisement posted around antenatal clinics of three hospitals in NSLHD: Royal North Shore, Hornsby, and Manly Hospitals. The interviews were semi-structured, one-on-one, and in-person conducted by a trained female volunteer. The interviews were audio-recorded, transcribed into text. The data was analyzed via an inductive and descriptive coding approach. The codes were then categorized into main themes and sub-themes. Results: 30 women (7 Australian-born, 11 Chinese, 8 Indians, and 4 Koreans) partook the semi-structured interviews and 5 themes were identified: (1) Reaction to diagnosis; (2) Management issues; (3) Roles of friends and family; (4) Information access; and (5) Experience with healthcare services. The lack of culturally tailored dietary information, social support and language barriers were the main factors underpinning the differences in GDM experiences among women from CALD backgrounds versus Australian-born. Conclusion: Healthcare models should provide more emotional support upon diagnosis, culturally tailored guidelines for lifestyle modifications, and involve friends and family in care and management to enhance the experience of GDM for women from CALD backgrounds.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries.

INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (a basal insulin) and insulin aspart (a prandial insulin). The aim of this study was to investigate clinical outcomes in people with type 2 diabetes (T2D) after initiating IDegAsp treatment in a real-world setting. METHODS: This 26-week, open-label, non-interventional study was conducted in Australia, India, Malaysia, Philippines, Saudi Arabia, and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp from antidiabetic treatments (including oral antidiabetic drugs, basal insulin, basal-bolus insulin, premix insulin, and glucagon-like peptide 1 receptor agonist) per local clinical practice. RESULTS: Compared with baseline, there was significant improvement in HbA1c at end of study (EOS, first visit within weeks 26-36; estimated change - 1.4% [95% CI - 1.51; - 1.29]; P < 0.0001 [primary outcome]). From baseline to EOS, there were significant reductions in fasting plasma glucose (- 2.7 mmol/L [95% CI - 2.98; - 2.46]; P < 0.0001), body weight (- 1.0 kg [95% CI - 1.51; - 0.52]; P < 0.0001), and basal insulin dose in insulin-experienced participants (- 2.3 units [95% CI - 3.51; - 1.01]; P < 0.001). The incidence rates of non-severe (overall and nocturnal) and severe hypoglycaemia decreased significantly (P < 0.001) between the period before baseline and before EOS. CONCLUSION: In adults with T2D, initiating or switching to IDegAsp from previous antidiabetic treatment was associated with improved glycaemic control, lower basal insulin dose (in insulin-experienced participants), and lower rates of hypoglycaemia. TRIAL REGISTRATION: Clinical trial registration NCT04042441.

Analysis of Serum Advanced Glycation Endproducts Reveals Methylglyoxal-Derived Advanced Glycation MG-H1 Free Adduct Is a Risk Marker in Non-Diabetic and Diabetic Chronic Kidney Disease.

Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2-4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2-4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD.

A co-designed integrated kidney and diabetes model of care improves mortality, glycaemic control and self-care.

BACKGROUND: Current healthcare models are ill-equipped for managing people with diabetes and chronic kidney disease (CKD). We evaluated the impact of a new diabetes and kidney disease service (DKS) on hospitalization, mortality, clinical and patient-relevant outcomes. METHODS: Longitudinal analyses of adult patients with diabetes and CKD (Stages 3a-5) were performed using outpatient and hospitalization data from January 2015 to October 2018. Data were handled according to whether patients received the DKS intervention (n = 196) or standard care (n = 7511). The DKS provided patient-centred, coordinated multidisciplinary assessment and management of patients. Primary analyses examined hospitalization and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in estimated glomerular filtration rate (eGFR), glycated haemoglobin A1c (HbA1c), self-care and patient activation at 12 months. RESULTS: Patients who received the intervention had a higher hospitalization rate {incidence rate ratio [IRR] 1.20 [95% confidence interval (CI) 1.13-1.30]; P < 0.0001}, shorter median length of stay {2 days [interquartile range (IQR) 1-6] versus 4 days [IQR 1-9]; P < 0.0001} and lower all-cause mortality rate [IRR 0.4 (95% CI 0.29-0.64); P < 0.0001] than those who received standard care. Improvements in overall self-care [mean difference 2.26 (95% CI 0.83-3.69); P < 0.001] and in statin use and eye and feet examinations were observed. The mean eGFR did not change significantly after 12 months [mean difference 1.30 mL/min/1.73 m2 (95% CI -4.17-1.67); P = 0.40]. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12 months of follow-up, respectively. CONCLUSIONS: A co-designed, person-centred integrated model of care improved all-cause mortality, kidney function, glycaemic control and self-care for patients with diabetes and CKD.

Early protein C activation is reflective of burn injury severity and plays a critical role in inflammatory burden and patient outcomes.

BACKGROUND: Navigating the complexities of a severe burn injury is a challenging endeavour where the natural course of some patients can be difficult to predict. Straddling both the coagulation and inflammatory cascades that feature strongly in the burns systemic pathophysiology, we propose the pleiotropic protein C (PC) system may produce a viable biomarker to assist traditional evaluation methods for diagnostic and prognostic purposes. METHODS: We enrolled 86 patients in a prospective observational cohort study. Over three weeks, serial blood samples were taken and measured for PC, activated (A)PC, their receptor endothelial protein C receptor (EPCR), and a panel of inflammatory cytokines including C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-17. Their temporal trends were analysed alongside clinical factors including burn size, burn depth, presence of inhalational injury, and a composite outcome of requiring increased support. RESULTS: (i) APC increased from a nadir on Day 3 (2.3±2.1ng/mL vs 4.1±2.5ng/mL by Day 18, p<0.0005), only becoming appropriately correlated to PC from Day 6 onwards (r=0.412-0.721, p<0.05 for all Days 6-21). (ii) This early disturbance in the PC system was amplified in the more severe burns (≥30% total body surface area, predominantly full thickness, or with inhalational injury), which were characterised by a marked fall in PC activation (approximated by APC/PC ratio) and APC levels during Days 0-3 with low unchanged PC levels. Critically low levels of this cytoprotective agent was associated with greater inflammatory burden, as reflected by significantly elevated CRP, IL-6, and IL-8 levels in the more severe compared to less severe burns, and by negative correlations between both PC and APC with most inflammatory cytokines. (iii) Alongside clinical markers of severity at admission (burn size, burn depth, and presence of inhalational injury), only Day 0 APC/PC ratio (OR 1.048 (1.014-1.083), p=0.006), APC (OR 1.364 (1.032-1.803), p=0.029), PC (OR 0.899 (0.849-0.953), p<0.0005), and not any inflammatory cytokines were predictive markers of requiring increased support. Uniquely, decreased Day 0 PC was further individually associated with each increased total length of stay, ICU length of stay, intravenous fluid resuscitation, and total surgeries, as well as possibly mortality. CONCLUSION: An early functional depletion of the cytoprotective PC system provides a physiological link between severe burns and the cytokine storm, likely contributing to worse outcomes. Our findings on the changes in APC, PC and PC activation during this pathological state support APC and PC as early diagnostic and prognostic biomarkers, and provides a basis for their therapeutic potential in severe burn injuries.

ARISE-a prospective, non-interventional, single-arm study assessing clinical parameters associated with the use of insulin degludec/insulin aspart in patients with type 2 diabetes in real-world settings: rationale and design.

PURPOSE: IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world. METHODS: ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians' discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26-36) and the proportion of patients achieving the target HbA1c level of <7% at the study end, respectively. A mixed model for repeated measurements will analyse the primary endpoint. CONCLUSION: Between-country differences in the prescription patterns of glucose-lowering agents in people with T2D warrant examination of their clinical use in different geographical settings. The ARISE study is designed to assess the clinical use of IDegAsp from real world in six different countries. Findings from the ARISE study will supplement those of previous randomised controlled studies by establishing real-world evidence of IDegAsp use in the participating countries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04042441. Registered 02 August 2014, https://clinicaltrials.gov/ct2/show/NCT04042441.

Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes.

To determine whether continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) therapy from near-diagnosis of type 1 diabetes is associated with reduced glycaemic variability (GV) and altered microRNA (miRNAs) expression. Adolescents (74% male) within 3-months of diabetes diagnosis (n = 27) were randomized to CSII (n = 12) or MDI. HbA1c, 1-5-Anhydroglucitol (1,5-AG), high sensitivity C-peptide and a custom TaqMan qPCR panel of 52 miRNAs were measured at baseline and follow-up (median (LQ-UQ); 535 (519-563) days). There were no significant differences between groups in baseline or follow-up HbA1c or C-peptide, nor baseline miRNAs. Mean ± SD 1,5-AG improved with CSII vs. MDI (3.1 ± 4.1 vs. - 2.2 ± - 7.0 mg/ml respectively, P = 0.029). On follow-up 11 miRNAs associated with diabetes vascular complications had altered expression in CSII-users. Early CSII vs. MDI use is associated with lower GV and less adverse vascular-related miRNAs. Relationships with future complications are of interest.

Long-Term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study.

AIMS: To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. METHODS: In a post hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by chi square and ANOVA. Prospective associations between baseline to 2-year GV and subsequent vascular and mortality outcomes were analyzed using landmark logistic and Cox proportional hazards regression. RESULTS: Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration, and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 [95% CI, 1.01-1.03] P < 0.01; and HR 1.01 [95% CI, 1.00-1.01] P < 0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 [95% CI, 1.00-1.04]; and HR 1.01 [95% CI, 1.00-1.02], both P < 0.05). HbA1c CV associated with increased stroke (HR 1.03 [95% CI, 1.01-1.06) P < 0.01). Glucose CV associated with increased coronary events (HR 1.01 [95% CI, 1.00-1.02] P < 0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 [95% CI, 1.02-1.06]; and HR 1.01 [95% CI, 1.01-1.02], both P < 0.001) and noncardiovascular mortality (HR 1.05 [95% CI, (1.03-1.07]; and HR 1.02 [95% CI, 1.01-1.03], both P < 0.001). HbA1c CV associated with coronary mortality (HR 1.04 [95% CI, 1.01-1.07] P < 0.05). CONCLUSIONS: Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.

Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program.

BACKGROUND: Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes. METHODS: To assess whether eGFR declines <57% could detect canagliflozin's effects on renal outcomes, we conducted a post hoc study comparing effects of canagliflozin versus placebo on composite renal outcomes using sustained 57%, 50%, 40%, or 30% eGFR reductions in conjunction with ESKD and renal death. Because canagliflozin causes an acute reversible hemodynamic decline in eGFR, we made estimates using all eGFR values as well as estimates that excluded early measures of eGFR influenced by the acute hemodynamic effect. RESULTS: Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect. CONCLUSIONS: Declines in eGFR <57% may provide robust estimates of canagliflozin's effects on renal outcomes if the analysis controls for the drug's acute hemodynamic effect. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.

Amount and Type of Dietary Fat, Postprandial Glycemia, and Insulin Requirements in Type 1 Diabetes: A Randomized Within-Subject Trial.

OBJECTIVE: The American Diabetes Association recommends individuals with type 1 diabetes (T1D) adjust insulin for dietary fat; however, optimal adjustments are not known. This study aimed to determine 1) the relationship between the amount and type of dietary fat and glycemia and 2) the optimal insulin adjustments for dietary fat. RESEARCH DESIGN AND METHODS: Adults with T1D using insulin pump therapy attended the research clinic on 9-12 occasions. On the first six visits, participants consumed meals containing 45 g carbohydrate with 0 g, 20 g, 40 g, or 60 g fat and either saturated, monounsaturated, or polyunsaturated fat. Insulin was dosed using individual insulin/carbohydrate ratio as a dual-wave 50/50% over 2 h. On subsequent visits, participants repeated the 20-60-g fat meals with the insulin dose estimated using a model predictive bolus, up to twice per meal, until glycemic control was achieved. RESULTS: With the same insulin dose, increasing the amount of fat resulted in a significant dose-dependent reduction in incremental area under the curve for glucose (iAUCglucose) in the early postprandial period (0-2 h; P = 0.008) and increase in iAUCglucose in the late postprandial period (2-5 h; P = 0.004). The type of fat made no significant difference to the 5-h iAUCglucose. To achieve glycemic control, on average participants required dual-wave insulin bolus: for 20 g fat, +6% insulin, 74/26% over 73 min; 40 g fat, +6% insulin, 63/37% over 75 min; and 60 g fat, +21% insulin, 49/51% over 105 min. CONCLUSIONS: This study provides clinical guidance for mealtime insulin dosing recommendations for dietary fat in T1D.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

OBJECTIVE: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. DESIGN, SETTING: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. PARTICIPANTS: Patients aged 18 years or more admitted to hospital from EDs. INTERVENTION: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. MAIN OUTCOME MEASURE: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. RESULTS: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. CONCLUSION: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

The impact of an integrated diabetes and kidney service on patients, primary and specialist health professionals in Australia: A qualitative study.

BACKGROUND: To address guideline-practice gaps and improve management of patients with both diabetes and chronic kidney disease (CKD), we involved patients, health professionals and patient advocacy groups in the co-design and implementation of an integrated diabetes-kidney service. OBJECTIVE: In this study, we explored the experiences of patients and health-care providers, within this integrated diabetes and kidney service. METHODS: 5 focus groups and 2 semi-structured interviews were conducted amongst attending patients, referring primary health professionals, and attending specialist health professionals. Maximal variation sampling was used for both patients and referring primary health professionals to ensure an equal representation of males and females, and patients of different CKD stages. All discussions were audiotaped and transcribed verbatim, before being thematically analysed independently by 2 researchers. RESULTS: The mean age (SD) for specialist health professionals, primary care professionals and patients who participated was 45 (11), 44 (15) and 68 (5) years with men being 50%, 80% and 76% of the participants respectively. Key strengths of the diabetes and kidney service were noted to be better integration of care and a perception of improved health and management of health. Whilst some aspects of access such as time between referral and initial appointment and having fewer appointments improved, other aspects such as in-clinic waiting times and parking remained problematic. Specialist health professionals noted that health professional education could be improved. Patient self-management was also noted by to be an issue with some patients requesting more information and some health professionals expressing difficulty in empowering some patients. CONCLUSIONS: Health professionals and patients reported that a co-designed integrated diabetes kidney service improved integration of care and improved health and management of health. However, some aspects of the process of care, health professional education and patient self-management remained challenging.

Plasma protein C levels are directly associated with better outcomes in patients with severe burns.

Protein C circulates in human plasma to regulate inflammation and coagulation. It has shown a crucial role in wound healing in animals, and low plasma levels predict the presence of a wound in diabetic patients. However, no detailed study has measured protein C levels in patients with severe burns over the course of a hospital admission. A severe burn is associated with dysfunction of inflammation and coagulation as well as a significant risk of morbidity and mortality. The current methods of burn assessment have shortcomings in reliability and have limited prognostic value. The discovery of a biomarker that estimates burn severity and predicts clinical events with greater accuracy than current methods may improve management, resource allocation and patient counseling. This is the first study to assess the potential role of protein C as a biomarker of burn severity. We measured the plasma protein C levels of 86 patients immediately following a severe burn, then every three days over the first three weeks of a hospital admission. We also analysed the relationships between burn characteristics, blood test results including plasma protein C levels and clinical events. We used a primary composite outcome of increased support utilisation defined as: a mean intravenous fluid administration volume of five litres or more per day over the first 72 h of admission, a length of stay in the intensive care unit of more than four days, or greater than four surgical procedures during admission. The hypothesis was that low protein C levels would be negatively associated with increased support utilisation. At presentation to hospital after a severe burn, the mean plasma protein C level was 76 ± 20% with a range of 34-130% compared to the normal range of 70-180%. The initial low can be plausibly explained by impaired synthesis, increased degradation and excessive consumption of protein C following a burn. Levels increased gradually over six days then remained at a steady-state until the end of the inpatient study period, day 21. A multivariable regression model (Nagelkerke's R2 = 0.83) showed that the plasma protein C level on admission contributed the most to the ability of the model to predict increased support utilisation (OR = 0.825 (95% CI = 0.698-0.977), P = 0.025), followed by burn size (OR = 1.252 (95% CI = 1.025-1.530), P = 0.027), burn depth (partial thickness was used as the reference, full thickness OR = 80.499 (1.569-4129.248), P = 0.029), and neutrophil count on admission (OR = 1.532 (95% CI = 0.950-2.473), P = 0.08). Together, these four variables predicted increased support utilisation with 93.2% accuracy, 83.3% sensitivity and 97.6% specificity. However if protein C values were disregarded, only 49.5% of the variance was explained, with 82% accuracy, 63% sensitivity and 91.5% specificity. Thus, protein C may be a useful biomarker of burn severity and study replication will enable validation of these novel findings.

Patient-reported barriers and outcomes associated with poor glycaemic and blood pressure control in co-morbid diabetes and chronic kidney disease.

AIMS: In patients with comorbid diabetes and chronic kidney disease, the extent to which patient-reported barriers to health-care and patient reported outcomes influence the quality of health care is not well established. This study explored the association between patient-reported barriers to health-care, patient activation, quality of life and diabetes self-care, with attainment of glycaemic and blood pressure (BP) targets. METHODS: This cross-sectional study recruited adults with diabetes and CKD (eGFR 20 to <60 ml/min/1.73m2) across four hospitals. We combined clinical data with results from a questionnaire comprising measures of patient-identified barriers to care, the Patient Activation Measure (PAM), 12-Item Short Form Survey (SF-12), and the Summary of Diabetes Self-Care Activity (SDSCA). RESULTS: 199 patients, mean age 68.7 (SD 9.6), 70.4% male and 90.0% with type 2 diabetes were studied. Poor glycaemic control was associated with increased odds of patient reported "poor family support" (OR 4.90; 95% CI 1.80 to 13.32, p < 0.002). Poor BP control was associated with increased odds of patient reported, "not having a good primary care physician" (OR 6.01; 2.42 to 14.95, p < 0.001). The number of barriers was not associated with increased odds of poor control (all p > 0.05). CONCLUSIONS: Specific patient-reported barriers, lack of patient perceived family and primary care physician support, are associated with increased odds of poor glycaemic and blood pressure control respectively. Interventions addressing these barriers may improve treatment target attainment.

HbA1c variability in adults with type 1 diabetes on continuous subcutaneous insulin infusion (CSII) therapy compared to multiple daily injection (MDI) treatment.

OBJECTIVE: To determine if continuous subcutaneous insulin infusion (CSII) therapy is associated with lower glycated haemoglobin (HbA1c) variability (long-term glycaemic variability; GV) relative to multiple daily injection (MDI) treatment in adults with type 1 diabetes mellitus (T1DM). DESIGN: Retrospective audit. SETTING AND PARTICIPANTS: Clinic records from 506 adults with T1DM from two tertiary Australian hospitals. OUTCOME MEASURES: Long-term GV was assessed by HbA1c SD and coefficient of variation (CV) in adults on established MDI or CSII therapy, and in a subset changing from MDI to CSII. RESULTS: Adults (n=506, (164 CSII), 50% women, mean±SD age 38.0±15.3 years, 17.0±13.7 years diabetes, mean HbA1c 7.8%±1.2% (62±13 mmol/mol) on CSII, 8.0%±1.5% (64±16 mmol/mol) on MDI) were followed for 4.1±3.6 years. CSII use was associated with lower GV (HbA1c SD: CSII vs MDI 0.5%±0.41% (6±6 mmol/mol) vs 0.7%±0.7% (9±8 mmol/mol)) and CV: CSII vs MDI 6.7%±4.6% (10±10 mmol/mol) vs 9.3%±7.3% (14±13 mmol/mol), both p<0.001. Fifty-six adults (73% female, age 36±13 years, 16±13 years diabetes, HbA1c 7.8%±0.8% (62±9 mmol/mol)) transitioned from MDI to CSII. Mean HbA1c fell by 0.4%. GV from 1 year post-CSII commencement decreased significantly, HbA1c SD pre-CSII versus post-CSII 0.7%±0.5% (8±5 mmol/mol) vs 0.4%±0.4% (5±4 mmol/mol); p<0.001, and HbA1c CV 9.2%±5.5% (13±8 mmol/mol) vs 6.1%±3.9% (9±5 mmol/mol); p<0.001. CONCLUSIONS: In clinical practice with T1DM adults relative to MDI, CSII therapy is associated with lower HbA1c GV.