The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol

ABSTRACT: BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin </= 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level </= 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793

Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial

ABSTRACT: Iron deficiency without anemia (IDWA) is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of an iron treatment after blood donation. METHODS: One week after donation, we randomly assigned 154 female donors with IDWA aged <50 years to a 4-week oral treatment of ferrous sulfate vs. placebo. The main outcome was the change in the level of fatigue before and after the intervention. Also evaluated were aerobic capacity, mood disorder, quality of life, compliance and adverse events. Biological markers were hemoglobin and ferritin. RESULTS: Treatment effect from baseline to 4 weeks for hemoglobin and ferritin were 5.2 g/L (p < 0.01) and 14.8 ng/mL (p < 0.01) respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 to 0.6, p = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces. CONCLUSIONS: These data are valuable as they enable us to conclude that donors with IDWA after a blood donation would not clinically benefit from iron supplementation. Trial registration: NCT00689793

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. METHODS: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. RESULTS: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P&lt;5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P&lt;10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P&lt;10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P&lt;0.005). CONCLUSIONS: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.</p

An Online Influenza Surveillance System for Primary Care Workers in Switzerland: Observational Prospective Pilot Study

Système en ligne de surveillance de la grippe chez les professionnels actifs en médecine de famille en Suisse : une étude de faisabilité Contexte : Une meilleure compréhension de l'épidémiologie de la grippe chez les professionnels actifs en médecine de famille pourrait orienter les futures recommandations visant à prévenir la transmission dans ce contexte. Nous avons donc conçu une étude pilote afin d’évaluer la faisabilité d'un système en ligne de surveillance de la grippe parmi les professionnels travaillant dans ce contexte. Une telle approche est particulièrement pertinente dans le contexte de la pandémie COVID-19, car ses conclusions pourraient être applicables à d'autres maladies infectieuses ayant des mécanismes de transmission similaires. Objectif : Mettre en place un système en ligne de surveillance de la grippe parmi les professionnels actifs en médecine de famille. Méthodes : Les médecins et le personnel d'une permanence et de deux cabinets de médecine de famille sélectionnés ont été inclus dans une étude pilote prospective observationnelle pendant la saison grippale 2017-2018. Ils ont été invités à enregistrer d’éventuels symptômes d'un état grippal (EG) dans une enquête hebdomadaire en ligne adressée par courrier électronique, et à effectuer eux-mêmes un frottis naso-pharyngé en présence de symptômes. Les échantillons ont été testés par RT-PCR pour influenza A et B ainsi qu’un panel d'agents pathogènes respiratoires. Résultats : Parmi les membres du personnel éligibles, 58,2 % ont consenti à l'étude et 53,7 % ont finalement fourni des données. À partir du moment où tous les participants ont été inclus, le taux de réponse hebdomadaire à l'enquête est resté proche de 100 % jusqu'à la fin de l'étude. Sur 79 épisodes symptomatiques (moyenne de 2,2 par participant), 10 participants sur 7 ont présenté un épisode correspondant à la définition de cas d’EG (taux d'attaque de 19,4 %). Un frottis était positif pour influenza A H1N1 (taux d'attaque 2,8 %, 95CI 0,4 % - 18,3 %). La réalisation du frottis a été considérée comme relativement facile. Conclusions : La mise en place d’un système en ligne de surveillance de la grippe est possible chez les professionnels en médecine de famille. Cette méthodologie prometteuse pourra être utilisée dans de futures études à plus large échelle afin d'améliorer la compréhension de l'épidémiologie de la grippe et d'autres maladies telles que le COVID-19 dans le contexte de la médecine de famille et d'orienter les futures recommandations visant à prévenir la transmission. Une étude à plus large échelle devrait également permettre d'évaluer les infections asymptomatiques

Remodelling family medicine teaching at the University of Lausanne using a modified Delphi method

BACKGROUND: In the context of implementing a new framework for pre-graduate medical education in Switzerland (PROFILES) and the ongoing reform of the medical curriculum at the Faculty of Biology and Medicine of the University of Lausanne, we set out to determine the priority teaching themes of family medicine and to collect expert opinions about the most appropriate teaching methods for family medicine. Such data would contribute to the production of a coherent family medicine teaching programme encompassing its specificities as well as future challenges facing medicine in general. METHOD: We mapped the current family medicine courses at the Faculty of Biology and Medicine to obtain an overview of current learning objectives and teaching content priorities. We classified and analysed the lessons using the PROFILES grid and the principles of family medicine described by the World Organization of Family Doctors (WONCA). Then we used a modified Delphi method with a selected panel of experts and two consensus rounds to prioritise objectives for family medicine teaching at the University of Lausanne. After choosing the top objectives/activities for family medicine, subgroups of experts then discussed what would be the best teaching methods for family medicine at the University of Lausanne. RESULTS: The mapping of family medicine teaching at the University of Lausanne showed that current teaching addresses most of the primary topics of family medicine education. The modified Delphi method allowed us to identify priority themes for teaching family medicine at the University of Lausanne: (1) take a medical history and clinical examination; (2) doctor-patient relationship / patient-centred care; (3) clinical reasoning; (4) interprofessional collaboration; (5) care planning/ documentation; (6) shared decision-making; (7) communication; (8) cost-effective care; (9) health promotion; (10) assessment of urgency. The discussion with the experts identified the strengths and weaknesses of the various teaching modalities in family medicine education. Teaching should be structured, coherent and show continuity. Clinical immersion and small group teaching were the preferred teaching modalities. CONCLUSION: This approach made it possible to create the guidelines for restructuring the family medicine teaching curriculum at the University of Lausanne

Nanoscale Stoichiometric Analysis of a High-Temperature Superconductor by Atom Probe Tomography

The functional properties of the high-temperature superconductor Y1Ba2Cu3O7−δ (Y-123) are closely correlated to the exact stoichiometry and oxygen content. Exceeding the critical value of 1 oxygen vacancy for every five unit cells (δ>0.2, which translates to a 1.5 at% deviation from the nominal oxygen stoichiometry of Y7.7Ba15.3Cu23O54−δ) is sufficient to alter the superconducting properties. Stoichiometry at the nanometer scale, particularly of oxygen and other lighter elements, is extremely difficult to quantify in complex functional ceramics by most currently available analytical techniques. The present study is an analysis and optimization of the experimental conditions required to quantify the local nanoscale stoichiometry of single crystal yttrium barium copper oxide (YBCO) samples in three dimensions by atom probe tomography (APT). APT analysis required systematic exploration of a wide range of data acquisition and processing conditions to calibrate the measurements. Laser pulse energy, ion identification, and the choice of range widths were all found to influence composition measurements. The final composition obtained from melt-grown crystals with optimized superconducting properties was Y7.9Ba10.4Cu24.4O57.2