Patients’ experiences of dialysis services: are national health strategy targets being met?

Background The National Health Strategy envisages a health system incorporating patient views; and providing accessible, consultant-led dialysis services with patient choice of dialysis modality, in all regions. Aims To describe patients’ experiences of renal services against National Health Strategy objectives. Methods Telephone interviews with 192 dialysis patients from three hospitals in the Eastern region. Results One-quarter of participants (16% of haemodialysis [HD] and 46% of peritoneal dialysis patients) lived outside the Eastern region, and travelled there because dialysis was not available locally. Two-thirds (65%) had a choice of dialysis modality. High satisfaction with interpersonal care was observed (83–98% satisfaction). Dissatisfaction with physical environment included parking (39–56%), waiting areas (62–69%), HD unit space (74%). Regarding support services, dietary services were satisfactory (92–95%), with lower satisfaction ratings for social and financial support services (62%). Conclusions Structural and management issues must be addressed to advance a quality agenda for renal care in Ireland.     

Interim PET/CT-based prognostic model for the treatment of diffuse large B cell lymphoma in the post-rituximab era

The prognostic accuracy of interim ¹⁸F-fluoro-2-dexoy-d-glucose positron emission tomography/computerized tomography (PET/CT) using three different methods of response assessments during rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy was investigated in 186 patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The response of interim PET/CT was assessed based on a combined evaluation of the Deauville five-point scale (5-PS), the rates of reduction in the maximal standardized uptake value (ΔSUVmax), and the rates of reduction in the metabolic tumor volume (ΔMTV2.5). Positivity on the 5-PS, the optimal cutoff of ΔSUVmax, or the optimal cutoff of ΔMTV2.5 could each predict disease progression. Over a median follow-up of 22.8 months, the assessment of responses based on the 5-PS, ΔSUVmax, and ΔMTV2.5 had prognostic value for progression-free survival. When patients were allocated a score of 0 to 3 depending on the presence of an inadequate response by visual, ΔSUVmax, or ΔMTV2.5, the outcomes of patients with a score of 0 were significantly superior to those with a score of 1, 2, or 3. The interim PET/CT response based on visual, SUV-based, and MTV-based assessment had significant negative predictive value for disease progression and a high potential for predicting outcomes of patients with DLBCL.     

Epigenome‐wide DNA methylation changes with development of arsenic‐induced skin lesions in Bangladesh: A case–control follow‐up study

Studies have found an association between aberrant DNA methylation and arsenic‐induced skin lesions. However, little is known about DNA methylation changes over time in people who develop arsenic‐induced skin lesions. We sought to investigate epigenome‐wide changes of DNA methylation in people who developed arsenic‐induced skin lesions in a 10‐year period. In 2009–2011, we conducted a follow‐up study of 900 skin lesion cases and 900 controls and identified 10 people who developed skin lesions since a baseline survey in 2001–2003. The 10 cases (“New Cases”) were matched with 10 controls who did not have skin lesions at baseline or follow‐up (“Persistent Controls”). Drinking water and blood samples were collected, and skin lesion was diagnosed by the same physician at both time points. We measured DNA methylation in blood using Infinium HumanMethylation450K BeadChip, followed by quantitative validation using pyrosequencing. Two‐sample t‐tests were used to compare changes in percent methylation between New Cases and Persistent Controls. Six CpG (cytosine‐phosphate‐guanine) sites with greatest changes of DNA methylation over time among New Cases were further validated with a correlation of 93% using pyrosequencing. One of the validated CpG site (cg03333116; change of %methylation was 13.2 in New Cases versus ?0.09 in Persistent Controls; P < 0.001) belonged to the RHBDF1 gene, which was previously reported to be hypermethylated in arsenic‐exposed cases. We examined DNA methylation changes with the development of arsenic‐induced skin lesions over time but nothing was statistically significant given the small sample size of this exploratory study and the high dimensionality of data. Environ. Mol. Mutagen. 55:449–456, 2014. © 2014 Wiley Periodicals, Inc.     

Advanced glycation end-products and receptor for advanced glycation end-products expression in patients with idiopathic pulmonary fibrosis and NSIP

Advanced glycation end products (AGEs) are associated with the pathogenesis of various diseases. AGEs induce excess accumulation of extracellular matrix and expression of profibrotic cytokines. In addition, studies on receptor for advanced glycation end products (RAGE) have shown that the ligand-RAGE interaction activates several intracellular signaling cascades associated with several fibrotic diseases. We investigated the expression of AGEs and RAGE in samples from patients with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP). Lung tissues and plasma samples from patients with IPF (n=10), NSIP (n=10), and control subjects (n=10) were obtained. Expression of AGEs and RAGE was determined by immunofluorescence assay of lung tissue. Circulating AGEs were measured by Western blot and enzyme-linked immunosorbent assay. Lungs with IPF showed strong expression for both AGEs and RAGE compared to that in NSIP and controls. However, no difference in AGE or RAGE expression was observed in lungs with NSIP compared to that in the controls. Levels of circulating AGEs also increased significantly in lungs of patients with IPF compared to those with NSIP and normal control. Increased AGE-RAGE interaction may play an important role in the pathogenesis of IPF.     

Allopurinol-induced DRESS syndrome mimicking biliary obstruction

An 84-year-old man was admitted to our hospital with fever, jaundice, and itching. He had been diagnosed previously with chronic renal failure and diabetes, and had been taking allopurinol medication for 2 months. A physical examination revealed that he had a fever (38.8℃), jaundice, and a generalized maculopapular rash. Azotemia, eosinophilia, atypical lymphocytosis, elevation of liver enzymes, and hyperbilirubinemia were detected by blood analysis. Magnetic resonance cholangiography revealed multiple cysts similar to choledochal cysts in the liver along the biliary tree. Obstructive jaundice was suspected clinically, and so an endoscopic ultrasound examination was performed, which ruled out a diagnosis of obstructive jaundice. The patient was diagnosed with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome due to allopurinol. Allopurinol treatment was stopped and steroid treatment was started. The patient died from cardiac arrest on day 15 following admission.     

治疗性单克隆抗体药动学相互作用的风险评估策略

生物制剂可用于治疗各种疾病,包括肿瘤、风湿、胃肠道疾病、皮肤科疾病、呼吸道疾病、激素缺乏症和感染。尽管近来批准了很多生物制品,但有关其药物间相互作用临床研究还不多。单克隆抗体是最主要的一类治疗性生物制品,本文介绍评价其药物间相互作用的风险评估策略,指出了评估中的关键因素,并建议将相互作用风险评估作为治疗性生物制品综合药物开发的一部分。