Aims/hypothesis Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. Methods We performed a 12 month randomised placebocontrolled study of the effects of treatment with the Cu (II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n=15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM bsa ) was the primary endpoint variable.Results Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM bsa by 5.0± 7.2 g/m 2 (mean ±SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p=0.0056 compared with placebo) and by 10.6± 7.6 g/m 2 at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p=0.0088), whereas LVM bsa was unchanged by placebo treatment. In a multiple-regression model that explained~75% of variation (R 2 =0.748, p=0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM bsa . Conclusions/interpretation Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease.

SummaryA safety-orientated system of delivering parenteral anaesthetic drugs was assessed in a prospective incident monitoring study at two hospitals. Anaesthetists completed an incident form for every anaesthetic, indicating if an incident occurred. Case mix data were collected and the number of drug administrations made during procedures estimated. From February 1998 at Hospital A and from June 1999 at Hospital B, until November 2003, 74 478 anaesthetics were included, for which 59 273 incident forms were returned (a 79.6% response rate). Fewer parenteral drug errors occurred with the new system than with conventional methods (58 errors in an estimated 183 852 drug administrations (0.032%, 95% CI 0.024-0.041%) vs 268 in 550 105 (0.049%, 95% CI 0.043-0.055%) respectively, p = 0.002), a relative reduction of 35% (difference 0.017%, 95% CI 0.006-0.028%). No major adverse outcomes from these errors were reported with the new system while 11 (0.002%) were reported with conventional methods (p = 0.055). We conclude that targeted system re-design can reduce medical error.

BackgroundAcetaminophen is often used with a non-steriodal anti-inflammatory drug for acute pain. Hitherto, these drugs have had to be given separately, typically at different time intervals. Maxigesic® tablets combine acetaminophen and ibuprofen in clinically appropriate doses to simplify administration and dosage regimen. We compared this combination with each of the constituent drugs for the relief of pain after extraction of third molar teeth.MethodsAdults (more than 16 yr) having one or more wisdom teeth removed under general or local anaesthesia were instructed to take two tablets before operation, then two tablets every 6 h for up to 48 h of: (i) a combination of acetaminophen 500 mg and ibuprofen 150 mg per tablet (Maxigesic®); (ii) acetaminophen 500 mg per tablet alone; or (iii) ibuprofen 150 mg per tablet alone. The primary outcome measure was the area under the curve (AUC) of the 100 mm visual analogue scale pain measurements taken for up to 48 h after surgery, divided by time, at rest and on activity. Pharmacokinetic data were collected in a subset of patients.ResultsThe mean (sem) time-corrected AUC on rest and activity, respectively, were: combination group 22.3 (3.2) and 28.4 (3.4); acetaminophen group 33.0 (3.1) and 40.4 (3.3); and ibuprofen group 34.8 (3.2) and 40.2 (3.4); P<0.01 for each of the four comparisons of combination vs constituent drug. There was no pharmacokinetic interaction between acetaminophen and ibuprofen administered together.ConclusionsMaxigesic® tablets provide superior pain relief after oral surgery to acetaminophen or ibuprofen alone.

Our aim was to compare the one-year post-operative outcomes following retention or removal of syndesmotic screws in adult patients with a fracture of the ankle that was treated surgically. A total of 51 patients (35 males, 16 females), with a mean age of 33.5 years (16 to 62), undergoing fibular osteosynthesis and syndesmotic screw fixation, were randomly allocated to retention of the syndesmotic screw or removal at three months post-operatively. The two groups were comparable at baseline. One year post-operatively, there was no significant difference in the mean Olerud-Molander ankle score (82.4 retention vs 86.7 removal, p = 0.367), the mean American Orthopedic Foot and Ankle Society ankle-hindfoot score (88.6 vs 90.1, p = 0.688), the mean American Academy of Orthopedic Surgeons foot and ankle score (96.3 vs 94.0, p = 0.250), the mean visual analogue pain score (1.0 vs 0.7, p = 0.237), the mean active dorsiflexion (10.2° vs 13.0°, p = 0.194) and plantar flexion (33.6° vs 31.3°, p = 0.503) of the ankle, or the mean radiological tibiofibular clear space (5.0 mm vs 5.3 mm, p = 0.276) between the two groups. A total of 19 patients (76%) in the retention group had a loose and/or broken screw one year post-operatively. We conclude that removal of a syndesmotic screw produces no significant functional, clinical or radiological benefit in adult patients who are treated surgically for a fracture of the ankle.

Objective: To compare two low fat diets one rich in walnuts on parameters of lipid metabolism in a group of hyperlipidaemic subjects. Design: A randomised cross over study. Setting: Department of Human Nutrition, University of Otago, Dunedin, New Zealand Subjects: Twenty one men with mean (s.d) levels of total and LDL cholesterol of 6.58 (0.60) and 4.63 (0.58) respectively. Interventions: For two periods of four weeks subjects were asked to consume two low fat diets (fat 30% total energy), one containing, on average, 78 gad walnuts. Walnuts obtained through Lincoln University and the Walnut Growers Group (South Canterbury). Results: Participants reported a higher total fat intake on the walnut diet (38% compared with 30% on the low fat diet P`0.01) The most consistent change in fatty acid pro®le of triacylglycerol, phospholipid and cholesterol ester on the walnut diet was a signi®cant (P`0.01) increase in linoleic acid. Triacylglycerol linolenate also increased signi®cantly (P`0.01). Total and LDL cholesterol were lower on both experimental diets than at baseline, 0.25 mmolal and 0.36 mmolal respectively on the walnut diet and 0.13 mmolal and 0.20 mmolal respectively on the low fat diet. High density lipoprotein cholesterol was higher on both the walnut and low fat diets when compared to baseline (0.15 mmolal and 0.12 mmolal, respectively). When comparing the walnut and low fat diets only apo B was signi®cantly lower (P`0.05) on the walnut diet. Conclusions: Despite an unintended increase in the total fat intake on the walnut diet, fatty acid pro®le of the major lipid fractions showed changes which might be expected to reduce risk of cardiovascular disease. The reduction of apolipoprotein B suggests a reduction in lipoprotein mediated risk, the relatively low myristic acid content of both diets perhaps explaining the absence of more extensive differences in lipoprotein levels on the two diets.