Thomas Kjellström

OBJECTIVE: To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l) initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration. RESULTS: The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to 7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 +/- 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS: Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

OBJECTIVE: To determine the risk of subsequent cancer in patients with deep venous thrombosis confirmed by venography. DESIGN: Follow up of all patients who had venography for suspected deep venous thrombosis during 1984-88. Patients were traced through a cancer registry up to 1 January 1991. SUBJECTS: 4399 patients who had phlebography in one hospital. SETTING: General hospital in Malmö, Sweden, serving a population of 230,000. MAIN OUTCOME MEASURE: Number of cancers recorded. RESULTS: 4399 patients had venography for suspected deep venous thrombosis; 604 were known to have a malignancy at the time of venography and were excluded from further analysis. 1383 had deep venous thrombosis, 150 of whom subsequently developed cancer. 182 of the 2412 patients without thrombosis developed cancer. During the first six months after venography 66 patients with thrombosis developed malignancy compared with 37 patients without thrombosis (P < 0.0001). 38 of the cancers in the deep venous thrombosis group were detected by history, physical examination, and laboratory tests. Three patients had postoperative or post-traumatic deep venous thromboses. Only two of the remaining patients would have benefited from early detection by extensive screening. After six months the incidence of cancer was identical in patients with and without thrombosis. CONCLUSION: Deep venous thrombosis is associated with a significantly higher frequency of malignancy during the first six months after diagnosis. Malignancies can be found with simple clinical and diagnostic methods and extensive screening is not required.

The Second Consensus Conference on Stroke Management took place from 22 to 24 March 2006 in Helsingborg, Sweden. The meeting was arranged by the International Stroke Society, endorsed by the European Stroke Council and International Stroke Society, and co-sponsored by the WHO Regional Office for Europe. It was arranged in collaboration with the European Region of the World Confederation for Physical Therapy and the European Association of Neuroscience Nurses. The patients' organization Stroke Alliance for Europe also participated. The meeting adopted the Helsingborg Declaration 2006 on European Stroke Strategies, a statement of the overall aims and goals of five aspects of stroke management (organization of stroke services, management of acute stroke, prevention, rehabilitation, evaluation of stroke outcome and quality assessment) to be achieved by 2015.

OBJECTIVES: Lipid-lowering drugs as 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and cholestyramine are effective in reducing cardiovascular morbidity both in primary and secondary prevention. Patient compliance is an important determinant of the outcome of therapy. This study was designed to compare compliance with tolerance and lipid-lowering effectiveness of pravastatin and/or cholestyramine in primary care. DESIGN: Nine hundred and eighty nine women and 1047 men were randomized to treatment at 100 primary-care centres in Sweden. After dietary intervention, an eligible patient was randomly assigned to one of four programs of daily treatment: group Q, 16 g cholestyramine, group QP, 8 g cholestyramine and 20 mg pravastatin, group P20, 20 mg pravastatin or group P40, 40 mg pravastatin. RESULTS: In group Q, group QP, group P20 and group P40 the reductions in low density lipoprotein (LDL)-cholesterol were 26%, 36%, 27% and 32%. The dose actually taken was 91-95% of the prescribed for the pravastatin treatment groups and 77-88% for the cholestyramine groups. In the pravastatin and cholestyramine groups 76-78% and 44-53%, respectively, completed the trial. Only 8-27% of the patients reached a serum cholesterol target level of 5.2 mmol L-1. There was no difference in lipid-lowering effect between women and men. CONCLUSION: Pravastatin alone is efficacious and compliance is high, independent of dose. Combined treatment with cholestyramine and pravastatin had a better cholesterol lowering effect (although not statistically significant) than 40 mg pravastatin. Despite this, only 8-27% of the patients actually reached a serum cholesterol level of 5.2 mmol L-1. No unexpected serious adverse events were detected in any of the treatment groups. As predicted, the gastrointestinal disturbances were more common on cholestyramine treatment. These two factors suggest that an increase in the dosage of the HMG-CoA reductase inhibitor may be appropriate. Results from other studies indicate that there also might be other positive effects of statin treatment beyond cholesterol lowering.