Prevalence of and Predictive Factor for Abdominal Aortic Calcification in Thai Chronic Kidney Disease Patients

Presence and severity of cardiovascular calcifications strongly predict cardiovascular morbidity and mortality in patients with CKD. This multicenter, cross‐sectional study primarily aimed to determine prevalence of abdominal aortic calcification (AAC) detected by plain lateral abdominal radiograph, and secondarily aimed to assess predictive factors for AAC. Patients (N = 1500), aged 18–70 years, with CKD stages 3–5D for ≥3 months prior to evaluation, were enrolled at 24 study centers in Thailand; 54.3% were non‐dialysis patients. The prevalence of AAC was 70.6% and 70.8% in non‐dialysis and dialysis patients, respectively. Patient's advanced age and widening pulse pressure were identified as predictive factors for AAC ≥ 5 in non‐dialysis patients, while patient's age, history of coronary heart disease or diabetes, longer dialysis vintage, and increasing corrected serum calcium or high‐sensitivity C‐reactive protein were identified as such in dialysis patients. With additional regression having covariates in binary, corrected serum calcium ≥9.5 mg/dL gave an OR 1.974 (95% CI: 1.324–2.943) for AAC ≥ 5 among the dialysis patients. AAC in diabetes subgroup (N = 692) was additionally evaluated and found that it was prevalent at 84.7% with increased phosphorus as predictive factor (OR, 1.178; 95% CI: 1.032–1.344) and 1,25 (OH)₂ vitamin D as protective factor (OR, 0.983; 95% CI, 0.970–0.996). The prevalence of AAC in the Thai CKD population is lower than that reported in the literature, and yet the burden is prominent in patients coexisting with diabetes. Variable relationships identified in this study may guide preventive measures against cardiovascular complications in CKD patients.     

Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: Exploratory analysis of the GIM2 trial

Dose-dense adjuvant chemotherapy is standard of care in high-risk early breast cancer patients. However, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose-dense chemotherapy in HER2-positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node-positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose-dense) or 3 (standard-interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2-positive patients. The efficacy of dose-dense chemotherapy in terms of disease-free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2-positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow-up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2-positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose-dense chemotherapy was associated with a significant survival improvement in high-risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2-positive disease who received adjuvant trastuzumab.     

Amenamevir,a novel helicase–primase inhibitor,for treatment of herpes zoster: A randomized,double‐blind,valaciclovir‐controlled phase 3 study

Amenamevir is a potent helicase–primase inhibitor and a novel class of antiviral agent other than nucleoside compounds, such as aciclovir, valaciclovir and famciclovir. This study is the first randomized, double‐blind, valaciclovir‐controlled phase 3 study to evaluate the efficacy and safety of amenamevir in Japanese patients with herpes zoster when treated within 72 h after onset of rash. A total of 751 patients were randomly assigned to receive either amenamevir 400 mg or 200 mg p.o. once daily or valaciclovir 1000 mg three times daily (daily dose, 3000 mg) for 7 days. The primary efficacy end‐point was the proportion of cessation of new lesion formation by day 4 (“day 4 cessation proportion”). The day 4 cessation proportions for amenamevir 400 and 200 mg and valaciclovir were 81.1% (197/243), 69.6% (172/247) and 75.1% (184/245), respectively. Non‐inferiority of amenamevir 400 mg to valaciclovir was confirmed by a closed testing procedure. Days to cessation of new lesion formation, complete crusting, healing, pain resolution and virus disappearance were evaluated as secondary end‐points. No significant differences were observed in any of the treatment groups. Amenamevir 400 and 200 mg were well tolerated as well as valaciclovir. The proportions of patients who experienced drug‐related adverse events were 10.0% (25/249), 10.7% (27/252) and 12.0% (30/249) with amenamevir 400 and 200 mg and valaciclovir, respectively. In conclusion, amenamevir 400 mg appears to be effective and well tolerated for treatment of herpes zoster in immunocompetent Japanese patients.