Quality of diabetes care and coronary heart disease absolute risk in patients with type 2 diabetes mellitus in Australian general practice

Objective: To examine the quality of diabetes care and prevention of cardiovascular disease (CVD) in Australian general practice patients with type 2 diabetes and to investigate its relationship with coronary heart disease absolute risk (CHDAR). Methods: A total of 3286 patient records were extracted from registers of patients with type 2 diabetes held by 16 divisions of general practice (250 practices) across Australia for the year 2002. CHDAR was estimated using the United Kingdom Prospective Diabetes Study algorithm with higher CHDAR set at a 10 year risk of >15%. Multivariate multilevel logistic regression investigated the association between CHDAR and diabetes care. Results: 47.9% of diabetic patient records had glycosylated haemoglobin (HbA1c) >7%, 87.6% had total cholesterol >= 4.0 mmol/l, and 73.8% had blood pressure (BP) >= 130/85 mm Hg. 57.6% of patients were at a higher CHDAR, 76.8% of whom were not on lipid modifying medication and 66.2% were not on antihypertensive medication. After adjusting for clustering at the general practice level and age, lipid modifying medication was negatively related to CHDAR (odds ratio (OR) 0.84) and total cholesterol. Antihypertensive medication was positively related to systolic BP but negatively related to CHDAR (OR 0.88). Referral to ophthalmologists/optometrists and attendance at other health professionals were not related to CHDAR. Conclusions: At the time of the study the diabetes and CVD preventive care in Australian general practice was suboptimal, even after a number of national initiatives. The Australian Pharmaceutical Benefits Scheme (PBS) guidelines need to be modified to improve CVD preventive care in patients with type 2 diabetes.

Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity

Sulfate is required for detoxification of xenobiotics such as acetaminophen (APAP), a leading cause of liver failure in humans. The NaS1 sulfate transporter maintains blood sulfate levels sufficiently high for sulforiation reactions to work effectively for drug detoxification. In the present study, we identified two loss-of-function polymorphisms in the human NaS1 gene and showed the Nas1-null mouse to be hypersensitive to APAP hepatotoxicity. APAP treatment led to increased liver damage and decreased hepatic glutathione levels in the hyposulfatemic Nas1-null mice compared with that in normosulfatemic wild-type mice. Analysis of urinary APAP metabolites revealed a significantly lower ratio of APAP-sulfate to APAP-glucuronide in the Nas1-null mice. These results suggest hyposulfatemia increases sensitivity to APAP-induced hepatotoxicity by decreasing the sulfonation capacity to metabolize APAP. In conclusion, the results of this study highlight the importance of plasma sulfate level as a key modulator of acetaminophen metabolism and suggest that individuals with reduced NaS1 sulfate transporter function would be more sensitive to hepatotoxic agents.

Short-term and long-term cardiovascular actions of different doses of perindopril in the rabbit

Short-term (one week) and chronic (six week) cardiovascular effects of orally administered perindopril were examined in the rabbit to demonstrate if short-term results can predict chronic outcomes. In short-term treatment, five doses of perindopril were examined in random order separated by a one week recovery period in each of six rabbits. Two doses of perindopril which resulted in a moderate hypotensive effect (-14 mmHg) and no hypotensive effect, respectively, were then selected for long-term treatment. Each rabbit in the short-term study received perindopril in doses of 0.01, 0.06, 0.32, 1.8 and 10 mg kg(-1) day(-1) for a week at a time. Rabbits on long-term treatment received either 0.3 or 0.01 mg kg(-1) day(-1) perindopril for six weeks. All rabbits had their mean arterial blood pressure (MAP) and heart rate recorded throughout treatment. Plasma angiotensin I (AngI), perindoprilat, angiotensin converting enzyme (ACE) inhibition were also assayed. Perindopril treatment for one week produced a dose-dependent hypotensive effect with the threshold dose, 0.06 mg kg(-1) day(-1), producing a 6.5+/-1.8 mmHg fall in MAP. The highest dose (10.0 mg kg(-1) day(-1)) produced a large fall in blood pressure of -29.6+/-4.2 mmHg. The 0.01 and 0.06 mg kg(-1) day(-1) doses of perindopril produced an average 2.65 fold increase in plasma AngI levels compared to the initial control. The three higher doses (0.32-10.0 mg kg(-1) day(-1)) of perindopril produced an equivalent 5.7 fold increase in plasma AngI levels compared to the initial controls. However, over six weeks 0.01 mg kg(-1) day(-1) perindopril induced a similar decrease in MAP as the 30 fold higher dose (-9.3 mmHg compared to -11.7 mmHg,). This was in spite of a 3 fold difference in plasma perindoprilat concentrations between the high and low dose perindopril groups. Plasma ACE inhibition was >80% with both doses of perindopril. The results indicate that while perindopril decreases MAP in a dose-dependent manner in short-term (one week) periods, over longer treatment times (six weeks) low concentrations of perindopril, non-hypotensive with shortterm treatment, may be as anti-hypertensive as considerably higher doses. (C) 1996 The Italian Pharmacological Society.

Management of acute psychostimulant toxicity

Psychostimulants produce a broad range of effects. Adverse effects can exist on a spectrum of severity from minor symptoms to life threatening toxicity. Although regular use or use of high doses increases risk of adverse events, many adverse events requiring emergency intervention may occur even in the naïve user.