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Background: Clinical trials remain key to the development of evidence‐based medical practice. However, they are becoming increasingly complex, mainly in a multinational setting. To address these challenges, the European Union (EU) adopted the Clinical Trial Regulation EU No. 536/2014 (CTR). Once in force, the CTR will lead to more consistent rules and simplification of procedures for conducting clinical trials throughout the EU. Existing harmonization initiatives and "research infrastructures" for clinical trials may facilitate this process. This publication offers a snapshot of the current level of harmonization activities in academic clinical research in Europe. Methods: A survey was performed among the member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardized questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the harmonization of academic clinical research processes at national level, to facilitate the exchange of expertise and experience among countries, and to identify new fields of action. Results: Most scientific partners already have in place various working groups and harmonization activities at national level. Furthermore, they are involved in and open to sharing their know‐how and documents. Since harmonization was mainly a bottom‐up approach up until now, the extent and topics dealt with are diverse and there is only little cross‐networking and cross‐country exchange so far. Conclusions: Currently, the ECRIN member countries offer a very solid base and collaborative spirit for further aligning processes and exchanging best practices for clinical research in Europe. They can support a smooth implementation of the EU CTR and may act as single contact with consolidated expertise in a country. [ABSTRACT FROM AUTHOR]

Background: Limited data exist on human zinc absorption from wheat biofortified via foliar (FBW) or root (hydroponically fortified wheat, HBW) zinc application. Stable isotope labels added at point of consumption (extrinsic labeling) might not reflect absorption from native zinc obtained by intrinsic labeling.Objectives: We measured fractional and total zinc absorption (FAZ, TAZ) in FBW and HBW wheat, compared with control wheat (CW) and fortified wheat (FW). The effect of labeling method was assessed in HBW (study 1), and the effect of milling extraction rate (EXR, 80% and 100%) in FBW (studies 2 and 3).Methods: Generally healthy adults (n = 71, age: 18-45 y, body mass index: 18.5-25 kg/m2) were allocated to 1 of the studies, in which they served as their own controls. In study 1, men and women consumed wheat porridges colabeled intrinsically and extrinsically with 67Zn and 70Zn. In studies 2 and 3, women consumed wheat flatbreads (chapatis) labeled extrinsically. Zinc absorption was measured with the oral to intravenous tracer ratio method with a 4-wk wash-out period between meals. Data were analyzed with linear mixed models.Results: In study 1 there were no differences in zinc absorption from extrinsic versus intrinsic labels in either FW or HBW. Similarly, FAZ and TAZ from FW and HBW did not differ. TAZ was 70-76% higher in FW and HBW compared with CW (P < 0.01). In studies 2 and 3, TAZ from FW and FBW did not differ but was 20-48% higher compared with CW (P < 0.001). Extraction rate had no effect on TAZ.Conclusions: Colabeling demonstrates that extrinsic zinc isotopic labels can be used to accurately quantify zinc absorption from wheat in humans. Biofortification through foliar zinc application, root zinc application, or fortification provides higher TAZ compared with unfortified wheat. In biofortified wheat, extraction rate (100-80%) has a limited impact on total zinc absorption. These studies were registered on clinicaltrials.gov (NCT01775319). [ABSTRACT FROM AUTHOR]

In Switzerland, Pharmaceutical Medicine has existed as one of 46 physician specialties accredited by the Federal Office of Public Health for more than 20 years. As a medical-scientific discipline, our goal is to enable best possible therapeutic coverage for the benefit of patients and society through a medical need-based development and optimal use of medicinal products. The role of the specialist in Pharmaceutical Medicine is to closely collaborate with various stakeholders of the healthcare system in the context of the discovery, research, development and approval of new medicinal products, as well as safe and effective use of new and established medicinal products in daily clinical practice. The post-graduate training consists of 2 years of patient-related clinical work, followed by 3 years of vocational training at certified training centers in Pharmaceutical Medicine. This also includes completion of an academic post-graduate diploma in Pharmaceutical Medicine (30 ECTS) according to the IFAPP/PharmaTrain syllabus and a 1 day board exam. As part of an ongoing revision of the training curriculum, we are developing a Swiss Catalog of Core Competencies in Pharmaceutical Medicine (SC3-PM), based on the IFAPP competency framework for drug development specialists in industry. In this article we discuss how we adapt the scope of the IFAPP competency framework to better reflect such roles in academic institutions or regulatory bodies in Switzerland. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic steatohepatitis (NASH) is defined by liver inflammation and consecutive fibrotic damage caused by a deposition of fat in the liver. No licensed medical treatments exist and lifestyle modification is difficult to incorporate into everyday life. We investigated the efficacy and safety of a 48-week treatment with vitamin D3 in NASH patients. Methods: Histologically determined NASH patients with elevated alanine aminotransferase (ALT) and decreased 25-OH vitamin D level at baseline received vitamin D3 or placebo orally over a 48-week period. The primary endpoint of this study was the change in ALT from baseline to the end-of-treatment. Steatohepatitis was categorized according to the Steatosis, Activity and Fibrosis Score and disease activity was assessed using the NAFLD activity score. Results: Serum 25-OH vitamin D levels significantly increased only in the vitamin D3 group over the 48-week treatment phase indicating compliance. In contrast to placebo, patients in the vitamin D group had markedly decreased ALT levels after the end-of-treatment phase. A significant decrease during treatment with vitamin D was also observed for cytokeratin-18 fragments compared with placebo. The study was not powered to detect changes in histological score, hence only descriptive results for histopathological characteristics are available. Conclusions: Treatment with 2100 IE vitamin D q.d. over 48 weeks was well tolerated and led to a significant improvement of serum ALT levels in patients with hypovitaminosis D and histology-proven NASH as the primary endpoint together with a trend toward reduction of hepatic steatosis, which was not significant due to a small number of available biopsy specimens. [ABSTRACT FROM AUTHOR]

Background: Rice can be fortified with the use of hot or cold extrusion or coating, but the nutritional qualities of the resulting rice grains have never been directly compared.Objective: Using fortified rice produced by coating or hot or cold extrusion, we compared 1) iron and zinc absorption with the use of stable isotopes, 2) iron and zinc retention during cooking, and 3) starch microstructure.Methods: We conducted 2 studies in young women: in study 1 [n = 19; mean ± SD age: 26.2 ± 3.4 y; body mass index (BMI; in kg/m2): 21.3 ± 1.6], we compared the fractional iron absorption (FAFe) from rice meals containing isotopically labeled ferric prophosphate (57FePP), zinc oxide (ZnO), citric acid, and micronutrients fortified through hot extrusion (HER1) with rice meals fortified through cold extrusion containing 57FePP, ZnO, citric acid, and micronutrients (CER); in study 2 (n = 22; age: 24 ± 4 y; BMI: 21.2 ± 1.3), we compared FAFe and fractional zinc absorption (FAZn) from rice meals fortified through hot extrusion (HER2) compared with rice meals fortified through coating containing 57FePP, ZnO, a citric acid and trisodium cirate mixture (CA/TSC), and micronutrients (COR) relative to rice meals extrinsically fortified with ferrous sulfate (reference). Rice types HER1 and CER contained citric acid, whereas types HER2 and COR contained CA/TSC. We assessed retention during standardized cooking experiments and characterized the rice starch microstructure.Results: FAFe (95% CI) was greater from CER [2.2% (1.4%, 3.4%)] than from HER1 [1.2% (0.7%, 2.0%)] (P = 0.036). There was no difference in FAFe between HER2 [5.1% (3.7%, 7.1%)] and COR [4.0% (2.9%, 5.4%)] (P = 0.14), but FAFe from COR was lower than that from the reference meal [6.6% (4.9%, 9.0%)] (P = 0.003), and the geometric mean FAZn (95% CI) did not differ between HER2 [9.5% (7.9%, 11.6%)] and COR [9.6% (8.7%, 10.7%)] (P = 0.92). Cooking in a rice-to-water ratio of 1:2 resulted in iron and zinc retentions >80%, and cooking in excess water did not affect iron retention from hot-extruded rice but caused iron losses of 25% from CER and COR. Distinct variations in starch microstructure were found in CER and HER1.Conclusions: Iron absorption was 64% higher from CER than from hot-extruded rice, with no difference between COR compared with hot-extruded rice. Lower extrusion temperatures may generate a more readily digestible starch structure, allowing for greater iron release in vivo but lower mineral retention during cooking. This trial was registered at clinicaltrials.gov as NCT02176759. [ABSTRACT FROM AUTHOR]

Background: Biofortification of staple food crops is a promising strategy to combat zinc deficiency, and it is of particular interest for rice and crops that are not consumed as flours and therefore not suitable for postharvest fortification. Because zinc absorption is decreased by phytic acid (PA) and perhaps other dietary components, it is important to measure the absorption of zinc from a biofortified crop before determining its efficacy.Objective: In this study, we compared the zinc absorption from zinc-biofortified rice (hydroponically enriched with (70)Zn) with that from a control rice of the same variety fortified with (70)ZnSO4 at point of use to reach the same total zinc content of 1.1 mg/meal. Both rice meals had a PA:Zn molar ratio of 12.Methods: Fractional absorption of zinc (FAZ) was measured with the use of the double-isotope tracer ratio method in 16 apparently healthy adults [18-45 y old; BMI (in kg/m(2)) 19-25] who consumed 2 single meals at 4-wk intervals in random order in a crossover design.Results: The FAZ from the biofortified rice (mean ± SD: 25.1 ± 8.7%) did not differ significantly from that of the point-of-use fortified rice (mean ± SD: 20.8 ± 7.1%) (P = 0.08).Conclusions: These results suggest that the native zinc accumulated in the biofortified rice was readily released from the rice matrix and that its absorption by adults was influenced by PA and other food components in a similar way to the inorganic zinc compound added to the rice at point of use. Moreover, rice biofortification is likely to be as good as postharvest zinc fortification as an intervention strategy to combat zinc deficiency. This trial was registered at clinicaltrials.gov as NCT01633450. [ABSTRACT FROM AUTHOR]

Herpes labialis affects one third of the population. We evaluated the topical application of an antiviral compound, hydroxypropyl-β-cyclodextrin (2-HPβCD), in reducing herpes labialis relapses. In this double-blind, randomized, placebo-controlled trial, 40 patients were randomized to a polyethylene glycol (PEG) formulation containing 20% 2-HPβCD or to a vehicle control arm. The gel was applied to the lips twice daily for 6 months. The primary objective was reducing herpes relapses. Surprisingly, the drug group had significantly more relapses than the vehicle group (p = 0.003). While the median numbers of relapses in the preceding year were 12 in the vehicle group and 10 in the drug group, both groups experienced very few relapses during the 6-month treatment period, with a median of 0 in the vehicle group and a median of 2 in the drug group. The impressive reduction of relapses in both groups may be due to a placebo effect or due to the topical treatment with PEG. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to assess the predictive value of myocardial perfusion imaging with (13)N-ammonia positron emission tomography (PET) and coronary flow reserve (CFR) on long-term prognosis in patients with suspected myocardial ischemia. Background: No prognostic data exist on the predictive value of CFR and (13)N-ammonia PET. Methods: Perfusion and CFR were assessed in 256 patients using (13)N-ammonia PET, and follow-up was obtained in 245 (96%) patients. Sixteen early revascularized patients were excluded and 229 were assigned to normal versus abnormal perfusion or normal versus abnormal CFR (<2.0). Major adverse cardiac events (MACE) (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for cardiac reasons) were assessed using the Kaplan-Meier method. Cox proportional hazard regression was used to identify independent predictors for cardiac events. Results: During follow-up (5.4 +/- 2.2 years), 78 patients had at least 1 cardiac event, including 29 cardiac deaths. Abnormal perfusion (n = 126) was associated with a higher incidence of MACE (p < 0.001) and cardiac death (p < 0.05). In patients with normal perfusion, abnormal CFR was independently associated with a higher annual event rate over 3 years compared with normal CFR for MACE (1.4% vs. 6.3%; p < 0.05) and cardiac death (0.5% vs. 3.1%; p < 0.05). In abnormal perfusion, CFR remained predictive throughout the 10-year follow-up (p < 0.001). Conclusions: Perfusion findings in (13)N-ammonia PET and CFR are strong outcome predictors. CFR allows further risk stratification, suggesting a "warranty" period of 3 years if normal CFR is associated with normal perfusion. Conversely, in patients with abnormal perfusion, an impaired CFR has added value for predicting adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to assess the predictive value of myocardial perfusion imaging with 13N-ammonia positron emission tomography (PET) and coronary flow reserve (CFR) on long-term prognosis in patients with suspected myocardial ischemia. Background: No prognostic data exist on the predictive value of CFR and 13N-ammonia PET. Methods: Perfusion and CFR were assessed in 256 patients using 13N-ammonia PET, and follow-up was obtained in 245 (96%) patients. Sixteen early revascularized patients were excluded and 229 were assigned to normal versus abnormal perfusion or normal versus abnormal CFR (<2.0). Major adverse cardiac events (MACE) (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for cardiac reasons) were assessed using the Kaplan-Meier method. Cox proportional hazard regression was used to identify independent predictors for cardiac events. Results: During follow-up (5.4 ± 2.2 years), 78 patients had at least 1 cardiac event, including 29 cardiac deaths. Abnormal perfusion (n = 126) was associated with a higher incidence of MACE (p < 0.001) and cardiac death (p < 0.05). In patients with normal perfusion, abnormal CFR was independently associated with a higher annual event rate over 3 years compared with normal CFR for MACE (1.4% vs. 6.3%; p < 0.05) and cardiac death (0.5% vs. 3.1%; p < 0.05). In abnormal perfusion, CFR remained predictive throughout the 10-year follow-up (p < 0.001). Conclusions: Perfusion findings in 13N-ammonia PET and CFR are strong outcome predictors. CFR allows further risk stratification, suggesting a “warranty” period of 3 years if normal CFR is associated with normal perfusion. Conversely, in patients with abnormal perfusion, an impaired CFR has added value for predicting adverse outcomes. [Copyright &y& Elsevier]