Introduction of New South Wales adult subcutaneous insulin-prescribing chart in a tertiary hospital: its impact on inpatient glycaemic control.

BACKGROUND: Erratic blood glucose levels (BGL) are commonly observed amongst patients with diabetes mellitus during hospital admission. Patients on insulin therapy often do not have their doses titrated adequately by their team doctors during admission, and insulin is well known to be a high-risk medication prone to administration error. AIM: To assess the impact of a state-wide adult subcutaneous insulin-prescribing chart (ASCIPC) on glycaemic control and insulin-prescribing pattern in a tertiary hospital. METHODS: An audit on the clinical records of inpatients who were on subcutaneous insulin therapy in the first week of July 2014 (prior to ASCIPC, n = 56) and in the first week of July 2015 (10 months after introducing ASCIPC, n = 62) was conducted at Liverpool Hospital. RESULTS: Following the introduction of ASCIPC, fewer BGL readings were missed (9.1 vs 11.6%, P = 0.032), and medical officers were more likely to adjust insulin dosage (71.0 vs 42.6%, P = 0.002) when compared to baseline. Glycaemic control improved, with lower mean BGL (9.4 ± 2.0 vs 10.4 ± 2.6 mmol/L, P = 0.021) and a greater proportion of BGL within the normal range of 5-10 mmol/L (56.2 vs 47.7%, P = 0.041). Omission of insulin doses after ASCIPC remained common, with over 40% of patients having at least one dose of insulin omitted during the audit week. CONCLUSION: Our study showed that the introduction of ASCIPC had positive impacts on glycaemic management for patients on subcutaneous insulin therapy during admission. More work is required to reduce the rate of insulin omission and to improve further glycaemic control for inpatients.

The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other comorbidities on length of stay (LOS) and costs in patients with peripheral arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A retrospective study was conducted between January 2011 and July 2012 at a tertiary referral hospital in Sydney. Demographic, laboratory, and operative data were obtained from the Australasian Vascular Audit database and hospital diagnostic-related group (DRG) reports. Patients with confirmed PAD with or without DM requiring hospital admission for a diagnosis of claudication, rest pain, ulcer/gangrene, and infection that required lower limb surgical intervention were included. Associations between LOS, surgical procedure, and DRG were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients) were identified: 292 admissions with PAD and 276 admissions with PAD in conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 ± 13.7 days compared with 15 ± 18.2 days for PADDM (p < .01; 95% confidence interval 2.7-8.0). LOS and costs were greatest in patients with PADDM undergoing major amputation (37 ± 13.7 days; US$42,236; p < .01). Analysis of variance indicated that the best predictors of LOS were the presence of DM, bypass surgery, amputation, chronic kidney disease (CKD) stage V, infection, and emergency admission. Over 18 months, the estimated total inpatient costs associated with lower limb intervention for PAD with and without DM amounted to US$7,598,597. People with DM incurred greater inpatient costs, averaging US$1,912 more per episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The impact of diabetes as a comorbid condition in patients with PAD is significant, both clinically and economically. Factors that predict increased LOS in patients with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and emergency admission.

Expression of Aeromonas caviae polyhydroxyalkanoate synthase gene in Burkholderia sp. USM (JCM15050) enables the biosynthesis of SCL-MCL PHA from palm oil products.

AIMS: Burkholderia sp. USM (JCM15050) isolated from oil-polluted wastewater is capable of utilizing palm oil products and glycerol to synthesize poly(3-hydroxybutyrate) [P(3HB)]. To confer the ability to produce polymer containing 3-hydroxyhexanoate (3HHx), plasmid (pBBREE32d13) harbouring the polyhydroxyalkanoate (PHA) synthase gene of Aeromonas caviae (phaC(Ac)) was transformed into this strain. METHODS AND RESULTS: The resulting transformant incorporated approximately 1 ± 0·3 mol% of 3HHx in the polymer when crude palm kernel oil (CPKO) or palm kernel acid oil was used as the sole carbon source. In addition, when the transformed strain was cultivated in the mixtures of CPKO and sodium valerate, PHA containing 69 mol% 3HB, 30 mol% 3-hydroxyvalerate and 1 mol% 3HHx monomers was produced. Batch feeding of carbon sources with 0·5% (v/v) CPKO at 0 h and 0·25% (w/v) sodium valerate at 36 h yielded 6 mol% of 3HHx monomer by controlled-feeding strategies. CONCLUSIONS: Burkholderia sp. USM (JCM15050) has the metabolic pathways to supply both the short-chain length (SCL) and medium-chain length (MCL) PHA monomers. By transforming the strain with the Aer. caviae PHA synthase with broader substrate specificity, SCL-MCL PHA was produced. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study demonstrating the ability of transformant Burkholderia to produce P(3HB-co-3HHx) from a single carbon source.

Overview of endocrinopathies associated with ß-thalassaemia major.

BACKGROUND: Thalassaemia major is a common and serious medical problem worldwide that is associated with a range of complications, including effects on multiple endocrine pathways. Minimizing or preventing comorbidities is important for these individuals who need life-long multidisciplinary care and treatment. However, there are limited overviews of the endocrine complications associated with this illness, nor any consensus regarding management guidelines. METHOD: A retrospective cohort analysis of ß-thalassaemia patients attending an ambulatory transfusion clinic at Royal Prince Alfred Hospital was conducted from June 2008. RESULTS: All of our subjects (n=29) had at least one endocrinopathy present with 16 patients (55%) having three or more (≥3) endocrinopathies. Hypogonadism was the most prevalent followed by osteoporosis and growth failure (less than 3rd centile) with a frequency of 16/29 (55%), 14/29 (48%) and 10/29 (35%) patients respectively. Those with more endocrinopathies (≥3) had a longer duration of transfusion therapy when compared with those with fewer endocrinopathies. CONCLUSION: A summary of our clinical guidelines, which have been used to monitor and manage these complications, is presented along with a discussion on the results and pathophysiology of the associated endocrinopathies.

Investigating general medication prescription by general practitioners during a 12-month randomized controlled weight loss trial.

Much healthcare expenditure is on pharmaceutical drugs. Expenditure on medications has increased both in absolute terms, and as a proportion of total health expenditure. No previous studies have investigated the prescribing costs by general practitioners when managing patients during a weight loss intervention. This study evaluated the medication costs by individual class during a 1-year study in which 268 participants were randomized to one of two weight loss programmes, either standard care (SC) as defined by national guidelines, or a commercial provider (Weight Watchers) (CP). The baseline body mass index of participants (mean ± standard deviation) was 32.0 ± 2.5 kg m-2 , their body weight was 87.5 ± 11.8 kg, and age 47.4 ± 11.7 years. Weight loss for the SC and CP groups was -2.6 and -6.1 kg, respectively (between group difference; P < 0.0001). The greater weight loss in the CP group compared to SC was accompanied by larger reductions in waist circumference and fat mass. The CP group also had significantly greater improvements than SC in high-density lipoprotein cholesterol. Despite SC participants being prescribed and spending more on medications than the CP group with no better weight or metabolic outcomes, this was not of statistical significance. For both groups the highest proportion of prescriptions (≥30% of medications) was for control of risk factors for cardiovascular disease. In conclusion, this study indicates that obesity treatment via a shared care approach with a CP results in greater weight loss and some better clinical outcomes, but despite lower medication costs overall, this was not significant when compared to SC treatment.

An intragastric balloon produces large weight losses in the absence of a change in ghrelin or peptide YY.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: The development of obesity is a multi-factorial process that results in an alteration in the neuroendocrine hormones that help regulate appetite and body weight. Weight loss has been shown to alter this neuroendocrine balance so as to promote weight regain. An intragastric balloon is an effective method to achieve significant weight loss in obese patients and is well suited for those patients who are looking for an alternative to lifestyle modification alone, and those who are not ready or suitable for surgical intervention. Limited research has shown that the weight loss achieved with an intragastric balloon is mediated by altered secretion of the hormones that regulate appetite and weight. WHAT DOES THIS STUDY ADD?: There are currently limited data on the effects of intragastric balloons on appetite and weight-related hormones. In the current study, we have investigated a broad range of gut hormones and adipokines and their response to weight loss induced by differing methods, and the subsequent effect this may have on weight regain. This is an important research area as novel therapies and long-term strategies are needed to counteract the unfavourable changes to the neuroendocrine control of appetite and satiety associated with diet-induced weight loss. This study aims to determine the effect of weight loss achieved with different methods on fasting levels of appetite hormones. Sixty-six obese adults with metabolic syndrome were randomized to intragastric balloon (IGB) for 6 months, with a 12-month behavioural modification programme (IGB group, 'IGBG') or a 12-month behavioural modification programme alone (control group, 'CG'). Anthropometric assessments and blood samples were taken every 3 months and total ghrelin, peptide YY (PYY), adiponectin and leptin were measured. Significant weight-loss differences favouring the IGBG were evident between groups at all time points. Ghrelin increased when the IGB was in situ (+39.3 pmol L(-1) vs. baseline) and returned to baseline after its removal (-34.7 pmol L(-1) ). Adiponectin and PYY levels remained stable in the IGBG, with transient increases noted in the CG. There were no significant between-group differences for ghrelin, PYY or adiponectin. In the IGBG, despite a decrease in leptin at 6 months (-11.7 ng mL(-1) ), levels increased to baseline after IGB removal (-3.7 ng mL(-1) ). In summary, weight loss associated with the IGB did not alter fasting levels of PYY or adiponectin. There was a return of ghrelin and leptin levels to baseline values after IGB removal. No compensatory rise in ghrelin was evident in either group 12 months after initial weight reduction, suggesting that such treatment strategies may lead to better long-term sustainable weight loss.

Modulating multidrug resistance gene in leukaemia cells by short interfering RNA.

INTRODUCTION: The multidrug resistance gene, MDR1, is one of the genes responsible for resistance to chemotherapy in the treatment of leukaemia and other cancers. The discovery of RNA interference in mammalian cells has provided a powerful tool to inhibit the expression of this gene. However, very little is known about the transfection of leukaemia cells with short interfering RNA (siRNA) targeted at MDR1. This study aims to evaluate the effectiveness of two chemically-synthesised siRNA in modulating MDR1 gene and inhibiting P-glycoprotein expression in leukaemic cells. We also evaluated two siRNA delivery methods in this study. METHODS: K562/Adr was transfected with two MDR1-targeted siRNA or negative control siRNA, by using cationic lipid-based transfection reagents or electroporator. Gene expression of MDR1 was quantified by real-time polymerase chain reaction and calculated as a percentage relative to the negative control siRNA. P-glycoprotein expression was evaluated via flow cytometry and drug sensitivity after treatment was assessed by cytotoxicity assays. RESULTS: The percentage of MDR1 gene knockdown from cells transfected with an electroporator was significantly higher (84.4 percent, p-value is 0.094) compared to cells transfected with cationic lipid-based transfection reagents (52.8 percent). Both siRNA significantly reduced the expression of MDR1 by 84.9 percent (p-value is 0.001) and 86.0 percent (p-value is 0.011), respectively. P-glycoprotein expression was down-regulated and drug sensitivity was increased after treatment with the siRNA. CONCLUSION: This study shows that the two siRNA sequences are capable of modulating MDR1 and P-glycoprotein expressions and increased drug sensitivity. Transfection with an electroporator was superior to chemical transfection for leukaemia cells.