When innovation outpaces regulations:The legal challenges for direct-to-patient supply of investigational medicinal products

AIMS: We profile the lack of specific regulation for direct‐to‐patient postal supply (DTP) of clinical trial medications (investigational medicinal products, IMPs) calling for increased efficiency of patient‐centred multi‐country remote clinical trials. METHODS: Questionnaires emailed to 28 European Economic Area (EEA) Medical Product Licensing Authorities (MPLAs) and Swissmedic MPLA were analysed in 2019/2020. The questionnaire asked whether DTP of IMPs was legal, followed by comparative legal analysis profiling relevant national civil and criminal liability provisions in 30 European jurisdictions (including The Netherlands), finally summarising accessible COVID‐19‐related guidance in searches of 30 official MPLA websites in January 2021. RESULTS: Twenty MPLAs responded. Twelve consented to response publication in 2021. DTP was not widely authorised, though different phrases were used to explain this. Our legal review of national laws in 29 EEA jurisdictions and Switzerland did not identify any specific sanctions for DTP of IMPs; however, we identified potential national civil and criminal liability provisions. Switzerland provides legal clarity where DTP of IMPs is conditionally legal. MPLA webpage searches for COVID‐19 guidance noted conditional acceptance by 19 MPLAs. CONCLUSIONS: Specific national legislation authorising DTP of IMPs, defining IMP categories, and conditions permitting the postage and delivery by courier in an EEA‐wide clinical trial, would support innovative patient‐centred research for multi‐country remote clinical trials. Despite it appearing more acceptable to do this between EU Member States, provided each EU MPLA and ethics board authorises it, temporary Covid‐19 restrictions in national Good Clinical Practice (GCP) guidance discourages innovative research into the safety and effectiveness of clinical trial medications

Couple interdependence impacts HIV‐related health behaviours among pregnant couples in southwestern Kenya: a qualitative analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138409/1/jia21224.pd

Research Priorities for Endometriosis:Recommendations From a Global Consortium of Investigators in Endometriosis

The 3rd International Consensus Workshop on Research Priorities in Endometriosis was held in São Paulo on May 4, 2014, following the 12th World Congress on Endometriosis. The workshop was attended by 60 participants from 19 countries and was divided into 5 main sessions covering pathogenesis/pathophysiology, symptoms, diagnosis/classification/prognosis, disease/symptom management, and research policy. This research priorities consensus statement builds on earlier efforts to develop research directions for endometriosis. Of the 56 research recommendations from the 2011 meeting in Montpellier, a total of 41 remained unchanged, 13 were updated, and 2 were deemed to be completed. Fifty-three new research recommendations were made at the 2014 meeting in Sao Paulo, which in addition to the 13 updated recommendations resulted in a total of 66 new recommendations for research. The research recommendations published herein, as well as those from the 2 previous papers from international consensus workshops, are an attempt to promote high-quality research in endometriosis by identifying and agreeing on key issues that require investigation. New areas included in the 2014 recommendations include infertility, patient stratification, and research in emerging nations, in addition to an increased focus on translational research. A revised and updated set of research priorities that builds on this document will be developed at the 13th World Congress on Endometriosis to be held on May 17-20, 2017, in Vancouver, British Columbia, Canada.Peter A. W. Rogers, G. David Adamson, Moamar Al-Jefout, Christian M. Becker, Thomas M. D, Hooghe, Gerard A. J. Dunselman, Asgerally Fazleabas, Linda C. Giudice, Andrew W. Horne, M. Louise Hull, Lone Hummelshoj, Stacey A. Missmer, Grant W. Montgomery, Pamela Stratton, Robert N. Taylor, Luk Rombauts, Philippa T. Saunders, Katy Vincent, Krina T. Zondervan for the WES/WERF Consortium for Research Priorities in Endometriosi

Identification of Adropin as a Secreted Factor Linking Dietary Macronutrient Intake with Energy Homeostasis and Lipid Metabolism

Obesity and nutrient homeostasis are linked by mechanisms that are not fully elucidated. Here we describe a secreted protein, adropin, encoded by a gene, Energy Homeostasis Associated (Enho), expressed in liver and brain. Liver Enho expression is regulated by nutrition: lean C57BL/6J mice fed high-fat diet (HFD) exhibited a rapid increase, while fasting reduced expression compared to controls. However, liver Enho expression declines with diet-induced obesity (DIO) associated with 3 months of HFD or with genetically induced obesity, suggesting an association with metabolic disorders in the obese state. In DIO mice, transgenic overexpression or systemic adropin treatment attenuated hepatosteatosis and insulin resistance independently of effects on adiposity or food intake. Adropin regulated expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma, a major regulator of lipogenesis. Adropin may therefore be a factor governing glucose and lipid homeostasis, which protects against hepatosteatosis and hyperinsulinemia associated with obesity. © 2008 Elsevier Inc. All rights reserved

TranscriptomeBrowser: A Powerful and Flexible Toolbox to Explore Productively the Transcriptional Landscape of the Gene Expression Omnibus Database

International audienceAs public microarray repositories are constantly growing, we are facing the challenge of designing strategies to provide productive access to the available data.\ We used a modified version of the Markov clustering algorithm to systematically extract clusters of co-regulated genes from hundreds of microarray datasets stored in the Gene Expression Omnibus database (n = 1,484). This approach led to the definition of 18,250 transcriptional signatures (TS) that were tested for functional enrichment using the DAVID knowledgebase. Over-representation of functional terms was found in a large proportion of these TS (84%). We developed a JAVA application, TBrowser that comes with an open plug-in architecture and whose interface implements a highly sophisticated search engine supporting several Boolean operators (http://tagc.univ-mrs.fr/tbrowser/). User can search and analyze TS containing a list of identifiers (gene symbols or AffyIDs) or associated with a set of functional terms.\ As proof of principle, TBrowser was used to define breast cancer cell specific genes and to detect chromosomal abnormalities in tumors. Finally, taking advantage of our large collection of transcriptional signatures, we constructed a comprehensive map that summarizes gene-gene co-regulations observed through all the experiments performed on HGU133A Affymetrix platform. We provide evidences that this map can extend our knowledge of cellular signaling pathways

Health workers' views on quality of prevention of mother-to-child transmission and postnatal care for HIV-infected women and their children

<p>Abstract</p> <p>Background</p> <p>Prevention of mother-to-child transmission has been considered as not a simple intervention but a comprehensive set of interventions requiring capable health workers. Viet Nam's extensive health care system reaches the village level, but still HIV-infected mothers and children have received inadequate health care services for prevention of mother-to-child transmission. We report here the health workers' perceptions on factors that lead to their failure to give good quality prevention of mother-to-child transmission services.</p> <p>Methods</p> <p>Semistructured interviews with 53 health workers and unstructured observations in nine health facilities in Hanoi were conducted. Selection of respondents was based on their function, position and experience in the development or implementation of prevention of mother-to-child transmission policies/programmes.</p> <p>Results</p> <p>Factors that lead to health workers' failure to give good quality services for prevention of mother-to-child transmission include their own fear of HIV infection; lack of knowledge on HIV and counselling skills; or high workloads and lack of staff; unavailability of HIV testing at commune level; shortage of antiretroviral drugs; and lack of operational guidelines. A negative attitude during counselling and provision of care, treating in a separate area and avoidance of providing service at all were seen by health workers as the result of fear of being infected, as well as distrust towards almost all HIV-infected patients because of the prevailing association with antisocial behaviours. Additionally, the fragmentation of the health care system into specialized vertical pillars, including a vertical programme for HIV/AIDS, is a major obstacle to providing a continuum of care.</p> <p>Conclusion</p> <p>Many hospital staff were not being able to provide good care or were even unwilling to provide appropriate care for HIV-positive pregnant women The study suggests that the quality of prevention of mother-to-child transmission service could be enhanced by improving communication and other skills of health workers, providing them with greater support and enhancing their motivation. Reduction of workload would also be important. Development of a practical strategy is needed to strengthen and adapt the referral system to meet the needs of patients.</p

Firm insoles effectively reduce hemolysis in runners during long distance running - a comparative study

<p>Abstract</p> <p>Background</p> <p>Shock absorbing insoles are effective in reducing the magnitude and rate of loading of peak impact forces generated at foot strike during running, whereas the foot impact force during running has been considered to be an important cause of intravascular hemolysis in long distance runners. Objective of this study was to evaluate the intravascular hemolysis during running and compare the effect of two different types of insoles (Soft and Firm) on hemolysis.</p> <p>Methods</p> <p>Twenty male long and middle distance runners volunteered to participate in this study. We selected two insoles (Soft and Firm) according to their hardness level (SHORE 'A' scale). Participants were randomly assigned to the soft insole (group 1) and firm insole (group 2) group with ten athletes in each group. Each athlete completed one hour of running at the calculated target heart rate (60-70%). Venous blood samples were collected before and immediately after running. We measured unconjucated bilirubin (mg/dl), lactate dehydrogenase (μ/ml), hemoglobin (g/l) and serum ferritin (ng/ml) as indicators of hemolysis.</p> <p>Results</p> <p>Our study revealed a significant increase in the mean values of unconjucated bilirubin (P < 0.05) while running with soft insoles indicating the occurrence of hemolysis in this group of athletes. Graphical analysis revealed an inverse relationship between hardness of insoles and hemolysis for the observed values.</p> <p>Conclusion</p> <p>Our results indicate that intravascular hemolysis occurs in athletes during long distance running and we conclude that addition of firm insoles effectively reduces the amount of hemolysis in runners compared to soft insoles.</p

Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice

The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice.These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health

Preparation of radioactive rare earth targets for neutron capture study

The understanding of thc details of nucleosynthesis in stars remains a great challenge. Though the basic mechanisms governing the processes have been known since the pioneering work of Burbidge, Burbidge, Fowler and Hoyle (l), we are now evolving into a condition where we can ask more specific questions. Of particular interest are the dynamics of the s ('slow') process. In this process the general condition is one in which sequential neutron captures occur at time scales long compared with the beta decay half lives of the capturing nuclides. The nucleosynthesis period for C or Ne burning stellar shells is believed to be in the year to few year time frame (2). This means that radionuclides with similar half lives to this burning period serve as 'branch point' nuclides. That is, there will be a competition between a capture to the next heavier isotope and a beta decay to the element of nexl higher atomic number. By understanding the abundances of these competing reactions we can learn about the dynamics of the nucleosynthesis process in the stellar medium. Crucial to this understanding is that we have a knowledge of the underlying neutron reaction cross sections on these unstable nuclides in the relevant stellar energy regions (neutrons of 0.1-100 KeV). Tm (1.9 years) and ls'Sm (90 ycws) have decay properties that permit their handling in an open fume hood. These Iwo were therefore selected to be the first radionuclides for neutron capture study in what will be an ongoing effort