The H1-receptor antagonist cetirizine ameliorates high-fat diet-induced glucose intolerance in male C57BL/6 mice,but not diabetes outcome in female non-obese diabetic (NOD) mice

Background It has been proposed that the histamine 1-receptor (H1-receptor) not only promotes allergic reactions, but also modulates innate immunity and autoimmune reactions. In line with this, we have recently reported that the H1-receptor antagonist cetirizine partially counteracts cytokine-induced beta-cell signaling and destruction. Therefore, the aim of this study was to determine whether cetirizine affects diabetes in NOD mice, a model for human type 1 diabetes, and glucose intolerance in high-fat diet C57BL/6 mice, a model for human glucose intolerance.Methods Female NOD mice were treated with cetirizine in the drinking water (25 mg/kg body weight) from 9 until 30 weeks of age during which precipitation of diabetes was followed. Male C57BL/6 mice were given a high-fat diet from 5 weeks of age. When the mice were 12 weeks of age cetirizine was given for 2 weeks in the drinking water. The effects of cetirizine were analyzed by blood glucose determinations, glucose tolerance tests, and insulin sensitivity tests.Results Cetirizine did not affect diabetes development in NOD mice. On the other hand, cetirizine treatment for 1 week protected against high-fat diet-induced hyperglycemia. The glucose tolerance after 2 weeks of cetirizine treatment was improved in high-fat diet mice. We observed no effect of cetirizine on the insulin sensitivity of high-fat diet mice.Conclusion Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction.     

The ECG in sarcoidosis – a marker of cardiac involvement? Current evidence and clinical implications

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas. Cardiac involvement is often limiting patients’ prognosis. Cardiac sarcoidosis can manifest with variant cardiac arrhythmias, of which atrioventricular (AV)-block-related bradycardia and ventricular tachycardias are the most common. Although cardiac sarcoidosis remains a histopathological diagnosis, the significance of imaging modalities, especially cardiac magnetic resonance imaging is increasing rapidly but mainly remains reserved for patients with a high suspicion due to a previous arrhythmia or unknown cardiomyopathy. Thus, there is a need for screening in daily clinical practice so that possible characteristic electrocardiographic (ECG) findings may guide the way to detect the disease.We therefore evaluated the ECG as a potential tool for screening of cardiac sarcoidosis and present different electrophysiological manifestations of cardiac sarcoidosis based on a literature review.The ECG is a valuable tool for screening of cardiac involvement in patients with sarcoidosis. Several parameters have been shown to be associated with cardiac involvement in sarcoidosis such as higher-degree AV-block, QRS complex fragmentation and widening, as well as certain T wave abnormalities that may indicate cardiac involvement, of which the latter two are most promising and specific. However, prospective studies examining a large number of trials are desirable.     

Advances in pharmacotherapy to treat kidney transplant rejection

Introduction: Current immunosuppressive combination therapy provides excellent prevention of T-cell-mediated rejection following renal transplantation; however, antibody-mediated rejection remains of high concern and accounts for a large number of long-term allograft losses. The recent development of protocol biopsies resulted in the definition of subclinical rejection (SCR), showing histologic evidence for rejection but unremarkable clinical course.

Areas covered: This review describes the current knowledge and evidence of pharmacotherapy to treat kidney allograft rejections and covers SCR treatment options. Each substance is analyzed with regard to its classical indication and further discussed for the treatment of other forms of rejection.

Expert opinion: Despite a lack of randomized trials, early acute T-cell-mediated rejection can be treated effectively in most cases without graft loss. The necessity to treat SCR is currently unclear. Due to a lack of effective therapies, new treatment approaches for antibody-mediated rejection are an urgent medical need to improve long-term outcomes. Future research should aim to better define pathophysiology and histology, stratify risk, and develop rational treatment strategies from randomized controlled trials, in order to establish the value of novel therapies in the arsenal of rejection pharmacotherapy. However, the effective prevention of rejection with minimal side effects still remains the goal in immunosuppression.     

Prospective payment systems and discretionary coding—Evidence from English mental health providers

Reimbursement of English mental health hospitals is moving away from block contracts and towards activity and outcome‐based payments. Under the new model, patients are categorised into 20 groups with similar levels of need, called clusters, to which prices may be assigned prospectively. Clinicians, who make clustering decisions, have substantial discretion and can, in principle, directly influence the level of reimbursement the hospital receives. This may create incentives for upcoding. Clinicians are supported in their allocation decision by a clinical clustering algorithm, the Mental Health Clustering Tool, which provides an external reference against which clustering behaviour can be benchmarked. The aims of this study are to investigate the degree of mismatch between predicted and actual clustering and to test whether there are systematic differences amongst providers in their clustering behaviour. We use administrative data for all mental health patients in England who were clustered for the first time during the financial year 2014/15 and estimate multinomial multilevel models of over, under, or matching clustering. Results suggest that hospitals vary systematically in their probability of mismatch but this variation is not consistently associated with observed hospital characteristics.