From Carbenes to Peroxidic Antimalarial Drugs. Highlights from the Scientific Work of Charles William Jefford.

A concise biography of C. W. Jefford, Professor of Chemistry in Geneva from 1969 to 1994, is given. A personal tribute by the author is paid to Jefford ' s fundamental work in the field of singlet oxygen, endo-peroxides, and 1,2,4-trioxanes as remedies against malaria.

Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the Anemia Correction in Diabetes (ACORD) Study.

BACKGROUND: Patients with diabetes and anemia are at high risk of cardiovascular disease. The Anemia CORrection in Diabetes (ACORD) Study aimed to investigate the effect of anemia correction on cardiac structure, function, and outcomes in patients with diabetes with anemia and early diabetic nephropathy. METHODS: One hundred seventy-two patients with type 1 or 2 diabetes mellitus, mild to moderate anemia, and stage 1 to 3 chronic kidney disease were randomly assigned to attain a target hemoglobin (Hb) level of either 13 to 15 g/dL (130 to 150 g/L; group 1) or 10.5 to 11.5 g/dL (105 to 115 g/L; group 2). The primary end point was change in left ventricular mass index (LVMI). Secondary end points included echocardiographic variables, renal function, quality of life, and safety. RESULTS: Median Hb level and LVMI were similar in groups 1 and 2 (Hb, 11.9 and 11.7 g/dL [119 and 117 g/L]; LVMI, 113.5 and 112.3 g/m(2), respectively). At study end, Hb levels were 13.5 g/dL (135 g/L) in group 1 and 12.1 g/dL (121 g/L) in group 2 (P < 0.001). No significant differences were observed in median LVMI at month 15 between study groups (group 1, 112.3 g/m(2); group 2, 116.5 g/m(2)). Multivariate analysis showed a nonsignificant decrease in LVMI (P = 0.15) in group 1 versus group 2. Anemia correction had no effect on the rate of decrease in creatinine clearance, but resulted in significantly improved quality of life in group 1 (P = 0.04). There were no clinically relevant differences in adverse events between study groups. CONCLUSION: In patients with diabetes with mild to moderate anemia and moderate left ventricular hypertrophy, correction to an Hb target level of 13 to 15 g/dL (130 to 150 g/L) does not decrease LVMI. However, normalization of Hb level prevented an additional increase in left ventricular hypertrophy, was safe, and improved quality of life.

Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Anaemia is associated with poor cancer control, particularly in patients undergoing radiotherapy. We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled trial in 351 patients (haemoglobin <120 g/L in women or <130 g/L in men) with carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received curative radiotherapy at 60 Gy for completely (R0) and histologically incomplete (R1) resected disease, or 70 Gy for macroscopically incompletely resected (R2) advanced disease (T3, T4, or nodal involvement) or for primary definitive treatment. All patients were assigned to subcutaneous placebo (n=171) or epoetin beta 300 IU/kg (n=180) three times weekly, from 10-14 days before and continuing throughout radiotherapy. The primary endpoint was locoregional progression-free survival. We assessed also time to locoregional progression and survival. Analysis was by intention to treat. FINDINGS: 148 (82%) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L (women) or 150 g/L (men) compared with 26 (15%) given placebo. However, locoregional progression-free survival was poorer with epoetin beta than with placebo (adjusted relative risk 1.62 [95% CI 1.22-2.14]; p=0.0008). For locoregional progression the relative risk was 1.69 (1.16-2.47, p=0.007) and for survival was 1.39 (1.05-1.84, p=0.02). INTERPRETATION: Epoetin beta corrects anaemia but does not improve cancer control or survival. Disease control might even be impaired. Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials.