Critical review of European Medicines Agency (EMA) assessment report and related literature on domperidone

European Medicines Agency (EMA) issued a final decision on September 01, 2014 that restricts the maximum daily dose of domperidone to 30 mg and treatment duration to 7 days. This paper presents a critical review of the scientific basis of the literatures having a role in the decision of EMA on domperidone with an approach based on statistical and epidemiological perspective. Although observational studies used by EMA were published, the EMA didn’t use an algorithm including “randomized clinical trials” according to evidence-based medicine when presenting their results. In conclusion, the results obtained from published studies are controversial, especially for the bias. From these publications, it cannot be concluded that domperidone exposure definitely increases the risk of “sudden cardiac death”, “death associated with ventricular arrhythmia” or “ventricular arrhythmia” The most concrete result of these studies is that the risk is higher with metoclopramide exposure compared to domperidone exposure.

     

Controlled Growth of Polyamide Films atop Homogenous and Heterogeneous Hydrogels Using Gel–Liquid Interfacial Polymerization

Controlled growth of crosslinked polyamide (PA) thin films is demonstrated at the interface of a monomer‐soaked hydrogel and an organic solution of the complementary monomer. Termed gel–liquid interfacial polymerization (GLIP), the resulting PA films are measured to be chemically and mechanically analogous to the active layer in thin film composite (TFC) membranes. PA thin films are prepared using the GLIP process on both a morphologically homogeneous hydrogel prepared from poly(2‐hydroxyethylmethacrylate) and a phase‐separated, heterogeneous hydrogel prepared from poly(acrylamide). Two monomer systems are examined: trimesoyl chloride (TMC) reacting with m‐phenylene diamine (MPD) and TMC reacting with piperazine (PIP). Unlike the self‐limiting growth behavior in TFC membrane fabrication, diffusion‐limited, continuous growth of the PA films is observed, where both the thickness and roughness of the PA layers increase with reaction time. A key morphological difference is found between the two monomer systems using the GLIP process; TMC/MPD produces a ridge‐and‐valley surface morphology whereas TMC/PIP produces nodule/granular structures. The GLIP process represents a unique opportunity to not only explore the pore characteristics (size, spacing, and continuity) on the resulting structure and morphology of the interfacially polymerized thin films, but also a method to modify the surface of (or encapsulate) hydrogels.     

Vascular Structure and Function in Cancer Survivors after Hematopoietic Stem Cell Transplantation

This study examined the effects of hematopoietic cell transplantation (HCT) and associated preparative regimens on vascular structure and function. Measures of carotid artery stiffness and brachial artery endothelial-dependent dilation were obtained in patients who had survived ≥ 2 years after HCT for hematologic malignancy and were diagnosed at ≤21 years. HCT survivors (n?=?108) were examined: 66 received total body irradiation (TBI) alone or with a low-dose cranial radiation boost (TBI±LD-CRT), 19 received TBI plus high-dose cranial radiation (TBI+HD-CRT), and 23 received a chemotherapy-only preparative regimen (CHEMO). Siblings (n?=?83) were invited to participate as control subjects. Although endothelial-dependent dilation did not differ between siblings and HCT survivors, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, and diameter distensibility were greater in siblings than HCT survivors. Comparing the HCT preparative regimens, carotid cross-sectional compliance, cross-sectional distensibility, diameter compliance, diameter distensibility, and incremental elastic modulus were significantly lower in the TBI+HD-CRT group compared with siblings or with TBI±LD-CRT and CHEMO treatment groups. Cross-sectional distensibility and diameter compliance were significantly lower in the TBI±LD-CRT group compared with siblings. TBI±LD-CRT and CHEMO groups did not differ from each other in these vascular measures. HCT preparative regimens containing TBI+HD-CRT resulted in greater arterial decrements, indicating increased risk for cardiovascular disease.