Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada

OBJECTIVES:

To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Association’s recommended targets in ambulatory patients with type 2 diabetes.

METHODS:

Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success – defined as the achievement of a blood pressure (BP) of 130/80 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmol/L and total cholesterol/high-density lipoprotein cholesterol ratio lower than 4.0 – are reported.

RESULTS:

Overall, 46% of individuals had a BP that was above the Canadian Diabetes Association’s recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose-lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterol/high-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C.

INTERPRETATION:

A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence-based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.     

Epilepsy in phenylketonuria: a complex dependence on serum phenylalanine levels

PURPOSE: Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism that frequently results in epilepsy if a low Phe diet was not implemented at birth. The mechanisms by which Phe affects the brain are poorly understood. METHODS: Audiogenic seizures (AGS) were studied in female homozygous Pah(enu2) BTBR (PKU) mice. RESULTS: Adult PKU mice, 18-20 weeks of age, in contrast to wild-type and heterozygous counterparts, exhibited a full range of AGS. Younger PKU mice, 5-7 weeks of age, had higher serum Phe levels (2.22 +/- 0.20 mM) in comparison with the adult animals (1.72 +/- 0.05 mM) and were not susceptible to AGS. Among adult mice, animals susceptible to AGS had significantly lower serum Phe levels (1.62 +/- 0.06 mM) in comparison with those resistant to AGS (1.86 +/- 0.07 mM). Susceptibility to AGS tended to increase in the afternoon when serum Phe concentration decreased in comparison to evening and morning. Normalization of serum Phe level by instituting a low Phe diet generally prevented susceptibility to AGS within 12 h. Although return to a standard diet raised Phe levels to hyperphenylalaninemic within 12 h in animals treated with a low Phe diet for 2 weeks, more than 7 weeks were needed for a complete resumption of AGS. CONCLUSIONS: Transient decrease in Phe levels within hyperphenylalaninemic range may be a necessary condition for PKU-related seizures to occur. A low Phe diet prevents susceptibility to seizures, which can resume with the significant delay after termination of dietary treatment.     

Use of handheld computers with global positioning systems for probability sampling and data entry in household surveys

We introduce an innovative method that uses personal digital assistants (PDAs) equipped with global positioning system (GPS) units in household surveys to select a probability-based sample and perform PDA-based interviews. Our approach uses PDAs with GPS to rapidly map all households in selected areas, choose a random sample, and navigate back to the sampled households to conduct an interview. We present recent field experience in two large-scale nationally representative household surveys to assess insecticide-treated bed net coverage as part of malaria control efforts in Africa. The successful application of this method resulted in statistically valid samples; quality-controlled data entry; and rapid aggregation, analyses, and availability of preliminary results within days of completing the field work. We propose this method as an alternative to the Expanded Program on Immunization cluster sample method when a fast, statistically valid survey is required in an environment with little census information at the enumeration area level.     

Olanzapine plus carbamazepine v. carbamazepine alone in treating manic episodes

BACKGROUND: Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania. AIMS: To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes. METHOD: Randomised, double-blind, 6-week trial of olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day; n=58) v. placebo plus carbamazepine (n=60) followed by open-label, 20-week olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day, n=86), with change in manic symptoms as main outcome measure. Safety and pharmacokinetics were also evaluated. RESULTS: There were no significant differences (baseline to endpoint) in efficacy measures between treatment groups, but at 6 weeks triglyceride levels were significantly higher (P=0.008) and potentially clinically significant weight gain (>or=7%) occurred more frequently (24.6% v. 3.4%, P=0.002) in the combined olanzapine and carbamazepine group. Carbamazepine reduced olanzapine concentrations but olanzapine had no effect on carbamazepine concentrations. CONCLUSIONS: The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern.