Biomarkers of diabetes risk in the National Diet and Nutrition Survey rolling programme (2008-2011).

This study describes the distribution of glycosylated haemoglobin (Hb(A1c)) and glucose concentrations in the combined year 1 (2008-2009), year 2 (2009-2010) and year 3 (2010-2011) of the National Diet and Nutrition Survey (NDNS) rolling programme. The NDNS rolling programme is a nationally representative survey of food consumption, nutrient intakes and nutritional status of people aged 1.5 years and over living in England, Wales, Scotland and Northern Ireland. The study population comprised survey members who completed three or four days of dietary recording and who provided a blood sample. After excluding survey members with self-reported diabetes (n=25), there were 1016 results for HbA1c and 942 for glucose (not the same individuals in each case). Around 5.4% of men and 1.7% of women aged 19-64 years, and 5.1% of men and 5.9% of women aged ≥65 years had impaired fasting glucose (glucose concentrations 6.1-6.9 mmol/L). Over 20% of men aged ≥65 years had fasting glucose concentrations above the clinical cut-off for diabetes (≥7 mmol/L) compared to 2.1% of women of similar age (p=0.007). Similarly, 16.4% of men had Hb(A1c) concentrations ≥6.5%, compared to 1.5% of women (p=0.003). Children and teenagers had fasting glucose and Hb(A1c) values largely within the normal range. To conclude, this is the first study to provide data on the distribution of HbA1c and glucose concentrations in a nationally representative sample of the British population. The high prevalence of men aged ≥65 years with Hb(A1c) and glucose concentrations above the clinical cut-off of diabetes warrants further attention.

Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26.

PURPOSE: Paclitaxel is an active drug for the treatment of breast cancer; however, the appropriate duration of administration is unknown. We assessed and compared the response rate, event-free survival, survival, and toxicity of paclitaxel 250 mg/m(2) delivered every 3 weeks as a 3-hour or 24-hour infusion. PATIENTS AND METHODS: A total of 563 women with stage IV or IIIB breast cancer were randomized into one of two groups: 279 received 3-hour paclitaxel and 284 received 24-hour paclitaxel. Patients were stratified by age, stage of disease, and prior therapy. RESULTS: A significantly higher rate of tumor response occurred in the first four cycles of therapy in patients who received the 24-hour infusion of paclitaxel (51% v 41%, respectively; P =.025). Tumor response over all cycles was also significantly higher in the group that received 24-hour infusion (54% v 44%, respectively; P =.023). There were no significant differences in event-free survival or survival between the two arms of the study (P =.9 and.8, respectively). No treatment by stage or by age interactions were observed. During the first four cycles of therapy, at least one episode of >/= grade 3 toxicity (excluding nadir hematologic values, alopecia, and weight change) occurred in 45% of patients who received the 3-hour paclitaxel infusion and in 50% of those who received the 24-hour paclitaxel infusion. Febrile neutropenia, >/= grade 3 infection, and >/= grade 3 stomatitis were less frequent, and severe neurosensory toxicity was more frequent in those who received the 3-hour paclitaxel infusion. Ten treatment-related deaths occurred in the first four cycles. Age, stage, and prior chemotherapy did not influence the effect of treatment. CONCLUSION: When administered as a continuous 24-hour infusion, high-dose paclitaxel results in a higher tumor response rate than when administered as a 3-hour infusion but does not significantly improve event-free survival or survival. Paclitaxel as a 24-hour infusion results in increased hematologic toxicity and decreased neurosensory toxicity.

High dose methotrexate infusion with leucovorin rescue for treatment of ectopic pregnancy.

The purpose of this article is to evaluate the effectiveness, side effects, and complications of high dose methotrexate infusion with leucovorin rescue in select patients with ectopic pregnancy. Between January 1991 and November 1994, 28 patients with ectopic pregnancies were prospectively treated with methotrexate (100 mg/m2 intravenous bolus followed by a 200 mg/m2 infusion over six hours) with leucovorin rescue. Twenty-seven of 28 patients (96%) were successfully treated. Only one patient (4%) required a second course of methotrexate to reach a normal hCG titer. One patient failed methotrexate infusion 45 days after treatment at a hCG titer of 12 mIU/mL. No Gynecologic Oncology Group grade 3 or 4 clinical, biochemical or hematologic toxicities occurred. Uterine bleeding and abdominal pain, not requiring transfusion or hospitalization, occurred in 71% and 56% of patients. The authors conclude that high dose methotrexate infusion with leucovorin rescue is a highly effective, well tolerated, nonsurgical treatment for select patients with ectopic pregnancy.

A clinical triad to diagnose paraneoplastic retinopathy.

Two elderly men developed photosensitivity and light-induced glare, transient visual symptoms, and progressive visual loss several months before small cell carcinoma of the lung was discovered. Both patients had impaired visual acuity and color vision, ring scotomas, and attenuated retinal arteriole caliber. Electroretinography demonstrated abnormal cone and rod-mediated responses. Antiretinal antibodies were identified in their serum. Their visual sensory function improved following therapy with immunosuppressive agents. The triad of photosensitivity, ring scotomatous visual field loss, and attenuated retinal arteriole caliber should alert one to a paraneoplastic disorder affecting the retina.

Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function.

cis-Diammine(1,1-cyclobutanedicarboxylato)platinum (CBDCA) is a nonnephrotoxic but myelosuppressive analogue of cisplatin (DDP) with greatly reduced protein binding and greatly increased renal excretion. Thus, CBDCA might produce undue toxicity in patients with decreased renal function. Twenty-two patients [14 females and 8 males; median age, 66 (range, 35 to 83); median Karnofsky performance status, 70 (range, 40 to 90)] with refractory tumors and renal dysfunction [creatinine clearance (CCr) 6 to 83 ml/min] were treated with 31 courses of i.v. bolus CBDCA every 4 to 5 weeks. Dosages were determined by pretreatment CCr. Patients with CCr greater than or equal to 40 ml/min received 400 mg/sq m; patients with CCr 20 to 39 ml/min received 250 mg/sq m; and patients with CCr 0 to 19 ml/min received 150 mg/sq m. Toxicities were assessed by weekly clinical and laboratory assessment. Responses were assessed in patients with measurable disease. Plasma pharmacokinetics and urinary excretion of total and ultrafilterable platinum were measured with flameless atomic absorption spectrometry. Observed toxicities were similar to those in patients with normal renal function. Myelosuppression, especially thrombocytopenia, was the major toxicity. Nausea and vomiting were mild to moderate. There was no ototoxicity, neurotoxicity, or nephrotoxicity or reduction in CCr due to CBDCA. Total body clearance of ultrafilterable platinum correlated highly with CCr. The percentage of reduction in platelet count correlated highly and linearly with the area under the curve (AUC) of plasma-ultrafilterable platinum. However, for any AUC, there was 17% greater platelet reduction in patients who had previously received extensive myelosuppressive chemotherapy than in nonpretreated patients. Since total body clearance is proportional to CCr, platelet reduction is proportional to AUC, and total body clearance = dosage/AUC, we have derived an equation to calculate a dosage that will produce a desired reduction in platelet count. Calculations for theoretical patients (both pretreated and nonpretreated) with CCr of 100 ml/min produce dosages very close to maximum tolerated dosages derived in actual Phase I trials. The actual clinical utility of these predictive equations must await validation in prospective studies with larger numbers of patients.