'Safety in the Grey Zone': Evaluation of a training program to improve the safety of incident responders on high-speed roads.

INTRODUCTION: Workers operating on high-speed roads (i.e., incident responders and emergency service workers) are at significant risk of being fatally injured while working. An identified gap in current prevention strategies is training focused on developing the skills of workers to effectively communicate and coordinate safety responses when operating on roads. METHODS: This study discusses the development of a program designed to optimize communication and coordination of safety practices at the scene of an incident on a high-speed road. The program is referred to as 'Safety in the Grey Zone.' The goal of the study is to present the results from an evaluation on its implementation across 23 sessions involving 158 participants from 7 incident response agencies in 1 state in Australia. RESULTS: The results of this study provide support for effectiveness in implementing the program as planned. The results also provide preliminary support for effectiveness of the program in achieving its learning outcomes as demonstrated by feedback received from participants following completion of the program. CONCLUSIONS: The findings of this study provide recommendations to consider in the program's future roll-out, as well as suggestions for future evaluations to assess the program's effectiveness in improving the safety of incident responders operating on high-speed roads.

Safety outcomes for incident responders operating on high speed roads: An analysis of the relationship with behaviour, motivation and role clarity.

High-speed roads present a considerable level of risk for frontline workers operating in these environments. To optimise safety, prevention activities need to target the key skills required to mitigate risk. The aim of this research was to explore the behavioural (compliance, participation, voice), motivational (safety motivation) and work demand (role clarity) factors that influence safety outcomes for incident responders working on high-speed roads. Safety outcomes included secondary incidents and near misses with passing vehicles. A total of 295 complete survey responses were received from six emergency service and incident response agencies in one Australian state. Data were analysed using structural equation modelling. The results showed that higher levels of safety voice, safety motivation and, role clarity were significantly associated with safer self-reported safety outcomes after controlling for the number of incidents attended. The findings from this study will be used to guide the development of a training program to improve the cognitive, behavioural and perceptual skills of incident responders operating on high-speed roads. Some insight into the structure and format of this program is provided.

Perioperative implications of sodium-glucose cotransporter-2 inhibitors: a case series of euglycemic diabetic ketoacidosis in three patients after cardiac surgery.

PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) comprise the newest class of oral hypoglycemic agents approved for treating type II diabetes mellitus (DM-II). Their use, however, has been associated with the rare development of euglycemic diabetic ketoacidosis (euDKA). We present three cases of euDKA that occurred following elective coronary artery bypass grafting surgery. The role of the anesthesiologist in the prevention, diagnosis, and management of this complication is also discussed. CLINICAL FEATURES: Three patients receiving chronic SGLT2i therapy for DM-II (discontinued one to two days preoperatively) underwent cardiac surgery. On the first postoperative day, each exhibited nausea, vomiting, and tachypnea. Although these nonspecific postoperative findings are common, our patients also exhibited anion gap metabolic acidosis (pH < 7.3, anion gap > 12 mmol·L-1) with lower than anticipated serum glucose levels of < 14 mmol·L-1. Serum and urine ketone analyses confirmed a diagnosis of euDKA. After insulin and dextrose infusions were initiated, rapid resolution of the metabolic abnormalities occured. CONCLUSIONS: Anesthesiologists should recognize that patients receiving SGLT2i preoperatively are at risk of developing euDKA. Hence, based on the pharmacokinetics of SGLT2i, discontinuing the medication at least two days prior to surgery should minimize the risk. Diagnosing euDKA is challenging and often delayed because of its nonspecific signs and symptoms. When suspected, serum and urine ketones should be monitored to reduce the time to diagnosis and treatment.

Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study.

BACKGROUND: Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM). METHODS: In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 microg for 4 weeks followed by 10 microg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR. RESULTS: Fifty-four subjects (28 exenatide, 26 placebo) were randomized and comprised the intent-to-treat population. Baseline values (exenatide and placebo) were (mean +/- SE) 74.4 +/- 2.1 and 74.5 +/- 1.9 beats/minute for HR, 126.4 +/- 3.2 and 119.9 +/- 2.8 mm Hg for systolic BP (SBP), and 75.2 +/- 2.1 and 70.5 +/- 2.0 mm Hg for diastolic BP (DBP). At 12 weeks, no significant change from baseline in 24-hour HR was observed with exenatide or placebo (LS mean +/- SE, 2.1 +/- 1.4 versus -0.7 +/- 1.4 beats/minute, respectively; between treatments, p = 0.16). Exenatide therapy was associated with trends toward lower 24-hour, daytime, and nighttime SBP; changes in DBP were similar between groups. No changes in daytime or nighttime rate pressure product were observed. With exenatide, body weight decreased from baseline by -1.8 +/- 0.4 kg (p < 0.0001; treatment difference -1.5 +/- 0.6 kg, p < 0.05). The most frequently reported adverse event with exenatide was mild to moderate nausea. CONCLUSIONS: Exenatide demonstrated no clinically meaningful effects on HR over 12 weeks of treatment in subjects with T2DM. The observed trends toward lower SBP with exenatide warrant future investigation. TRIAL REGISTRATION: NCT00516074.

Glycemic control with glyburide/metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial.

PURPOSE: To assess the efficacy and safety of adding rosiglitazone to an established regimen of glyburide/metformin in patients with type 2 diabetes who had not achieved adequate glycemic control (glycosylated hemoglobin [HbA1C] levels >7.0% and < or =10.0%). METHODS: Following an open-label, lead-in phase to optimize the dosing of glyburide/metformin tablets, 365 patients randomly received additive therapy comprising rosiglitazone (4 mg once daily) or placebo for 24 weeks. Based on glycemic response, rosiglitazone dose was maintained or increased to 4 mg twice daily. Glyburide/metformin dose was maintained or reduced by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change in HbA1C level from baseline to week 24. The proportions of patients achieving HbA1C levels <7% and a fasting plasma glucose level <126 mg/dL were also assessed. RESULTS: After 24 weeks, therapy with glyburide/metformin plus rosiglitazone resulted in a greater reduction in HbA1C levels (-1.0%, P<0.001) compared with combination therapy that included placebo, and in a larger proportion of patients (42% vs. 14%) who attained levels <7%. The difference in fasting plasma glucose levels between groups was -48 mg/dL (P<0.001), favoring glyburide/metformin plus rosiglitazone. The adverse event profile in the rosiglitazone-treated group included mild-to-moderate edema (8%), hypoglycemia (22%), and weight gain of 3 kg. No patient experienced hypoglycemia requiring third-party assistance. CONCLUSION: In patients with inadequate glycemic control despite established glyburide/metformin therapy, the addition of rosiglitazone improves glycemic control, allowing more patients to achieve an HbA1C level <7% and perhaps delaying the need for insulin treatment.

Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes.

Many patients with type 2 diabetes fail to achieve or maintain the American Diabetes Association's recommended treatment goal of glycosylated hemoglobin levels. This multicenter, double-blind trial enrolled patients with type 2 diabetes who had inadequate glycemic control [glycosylated hemoglobin A(1C) (A1C), >7% and <12%) with diet and exercise alone to compare the benefits of initial therapy with glyburide/metformin tablets vs. metformin or glyburide monotherapy. Patients (n = 486) were randomized to receive glyburide/metformin tablets (1.25/250 mg), metformin (500 mg), or glyburide (2.5 mg). Changes in A1C, fasting plasma glucose, fructosamine, serum lipids, body weight, and 2-h postprandial glucose after a standardized meal were assessed after 16 wk of treatment. Glyburide/metformin tablets caused a superior mean reduction in A1C from baseline (-2.27%) vs. metformin (-1.53%) and glyburide (-1.90%) monotherapy (P = 0.0003). Glyburide/metformin also significantly reduced fasting plasma glucose and 2-h postprandial glucose values compared with either monotherapy. The final mean doses of glyburide/metformin (3.7/735 mg) were lower than those of metformin (1796 mg) and glyburide (7.6 mg). First-line treatment with glyburide/metformin tablets provided superior glycemic control over component monotherapy, allowing more patients to achieve American Diabetes Association treatment goals with lower component doses in drug-naive patients with type 2 diabetes.

Increased myocardial perfusion and sympathoadrenal activation during mild core hypothermia in awake humans.

Potential mechanisms of cold-induced myocardial ischaemia are sympathetically mediated coronary vasoconstriction and/or catecholamine-induced increases in cardiac work. To examine these parameters, 11 human volunteers were each studied on one day with, and on another day without, beta-adrenoceptor blockade. On each day, warm (37 degrees C) saline (control) and cold (4 degrees C) saline (hypothermia) were given intravenously. Myocardial perfusion was assessed by positron emission tomography using H(2)(15)O, and coronary vascular resistance was calculated. Plasma catecholamines were measured to assess sympathoadrenal activation. The core temperature decreased by 1.0 +/- 0.2 degrees C with the cold saline, and was unchanged with warm saline. Myocardial perfusion increased by 20% (P = 0.01) and the rate-pressure product by 33% (P = 0.0004) with cold saline compared with warm saline. beta-Blockade eliminated these increases. Coronary vascular resistance was similar with warm and cold saline, and was unaffected by beta-blockade. Plasma adrenaline increased by 120% and noradrenaline by 251% during cold saline, but were unchanged during warm saline. In conclusion, core hypothermia triggers beta-adrenoceptor-mediated increased cardiac work, sympathoadrenal activation and increased myocardial perfusion. There is no evidence for hypothermia-induced coronary vasoconstriction.

Durability of efficacy and long-term safety profile of glyburide/metformin tablets in patients with type 2 diabetes mellitus: an open-label extension study.

BACKGROUND: Intensive glycemic control substantially reduces the microvascular and macrovascular complications of type 2 diabetes mellitus, although less than half of patients with diabetes achieve the target glycosylated hemoglobin (HbA1c) value recommended by the American Diabetes Association. Because monotherapy with an oral agent does not address the multiple pathophysiologic defects of diabetes, use of combination therapy appears to be warranted. A previous 32-week, randomized, double-blind, placebo-controlled trial found that treatment with glyburide/metformin tablets was associated with greater reductions in HbA1c values compared with glyburide monotherapy, metformin monotherapy, and placebo. OBJECTIVES: This study evaluated the durability of efficacy and long-term safety profile of therapy with glyburide/metformin tablets over 52 weeks. METHODS: Patients enrolled in this open-label extension study were drawn from 3 groups: those who completed the 32-week double-blind study, those who were discontinued from the double-blind study, and those who were ineligible for the double-blind study and were enrolled directly in the open-label extension study. Patients with an HbA1c of < 9% received glyburide/metformin 1.25 mg/250 mg tablets BID, and those with an HbA1c of > or = 9% received glyburide/metformin 2.5 mg/500 mg tablets BID. Primary efficacy variables included changes from baseline in HbA1c, fasting plasma glucose (FPG), and body weight at week 52. Safety was assessed based on adverse-event data and the results of physical examinations and laboratory tests. RESULTS: A total of 828 patients were enrolled in the study: 515 who completed the 32-week double-blind study, 138 who were discontinued from the double-blind study, and 175 who were directly enrolled. At week 52, the mean HbA1c value for the entire population had decreased from a baseline value of 8.73% to 7.04% (95% CI, -1.81 to -1.58). Patients who were enrolled directly had the poorest glycemic control at baseline and experienced the greatest reduction in HbA1c (-3.35%; 95% CI, -3.61 to -3.10). A reduction in mean FPG for the total population was observed as early as week 2, from 201 to 141 mg/dL (95% CI, -63.0 to -55.7). Symptoms of hypoglycemia occurred in 19.9% (165/828) of patients, although only one third of these patients had a documented finger-stick blood glucose value of > or = 50 mg/dL. CONCLUSIONS: In this 52-week, open-label extension study, glyburide/metformin tablets were well tolerated and effective in patients with type 2 diabetes. They provided rapid and sustainable reductions in HbA1c values and FPG concentrations.

Local sympathetic function in human skeletal muscle and adipose tissue assessed by microdialysis.

BACKGROUND: In response to stressors and pathophysiologic conditions, sympathetic neuronal outflows can change heterogeneously among body organs and tissues. This study examined the validity of microdialysis and measurements of microdialysate concentrations of catechols, to assess local sympathetic function in skeletal muscle and adipose tissue in humans. METHODS: Based on preliminary experiments, a microdialysate perfusion rate of 3 microl/min and collection duration of 30 minutes were chosen. To assess responses to a stimulus that increases sympathetic outflow to skeletal muscle, microdialysate norepinephrine and dihydroxyphenylglycol concentrations in quadriceps muscle, abdominal subcutaneous adipose tissue, and plasma were measured during orthostasis in 8 healthy normal volunteers. To assess responses to decreased postganglionic sympathetic nerve traffic, norepinephrine and dihydroxyphenylglycol concentrations were measured during i. v. infusion of trimethaphan in 5 volunteers. RESULTS: All subjects had detectable norepinephrine and dihydroxyphenylglycol in microdialysate from both skeletal muscle and adipose tissue. Orthostasis significantly increased microdialysate norepinephrine in skeletal muscle (0.38 +/- (SEM) 0.07 nmol/L supine to 1.48+/-0.24 nmol/L standing, p < 0.01) and in adipose tissue (0.31+/-0.02 nmol/L supine to 0.68+/-0.11 nmol/L standing, p < 0.01). Orthostasis also increased microdialysate dihydroxyphenylglycol in both tissues (1.76+/-0.30 nmol/L to 3.08+/-0.43 nmol/L, p < 0.01; 1.37+/-0.15 nmol/L supine to 1.99+/-0.34 nmol/L standing, p < 0.01). Trimethaphan decreased norepinephrine concentrations in skeletal muscle microdialysate by 50%, adipose tissue by 70%, and antecubital venous plasma 50%, with non-significant decreases in dihydroxyphenylglycol concentrations at each site. CONCLUSIONS: Microdialysate concentrations of norepinephrine and dihydroxyphenylglycol can be detected reliably and respond appropriately during manipulations that increase or decrease the sympathetically mediated release and turnover of norepinephrine. This approach may provide a means to assess sympathetic neuronal function in skeletal muscle and adipose tissue in humans with known or suspected dysautonomias.