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1. Community Use of Repurposed Drugs Before and During COVID-19 Pandemic in the Netherlands: An Interrupted Time-Series Analysis

Author

Zhou G, de Vos S, Schuiling-Veninga CC, Bos J, Oude Rengerink K, Pasmooij AMG, Mol PG, de Bock GH, and Hak E

Subjects
covid-19, drug utilization, repurposed drug, stringency index, Infectious and parasitic diseases, RC109-216
Abstract

Guiling Zhou,1 Stijn de Vos,1 Catharina CM Schuiling-Veninga,1 Jens Bos,1 Katrien Oude Rengerink,2 Anna Maria Gerdina Pasmooij,2 Peter GM Mol,2,3 Geertruida H de Bock,4 Eelko Hak1 1Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, Groningen, the Netherlands; 2Medicines Evaluation Board, Utrecht, the Netherlands; 3Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 4Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsCorrespondence: Guiling Zhou, Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, the Netherlands, Tel +31 503638707, Fax +31 503632772, Email g.zhou@rug.nlBackground: Repurposing registered drugs could reduce coronavirus disease (COVID-19) burden before novel drugs are authorized. Little is known about how the pandemic and imposed restrictions changed their dispensing. We aimed to investigate the impact of COVID-19 pandemic on repurposed drugs dispensing in the Netherlands.Methods: We performed interrupted time-series study using University of Groningen prescription database IADB.nl to evaluate dispensing trends of 24 repurposed drugs before (2017-February 2020) and after (March 2020– 2021) the pandemic’ start. Primary outcomes were monthly prevalence and incidence rates. An autoregressive integrated moving average model assessed the effect of pandemic and stringency index (measuring strictness of government’s restriction policies).Results: Annual number of IADB.nl population ranged from 919,697 to 952,400. Generally, dispensing of common long-term-used drugs was not significantly affected by pandemic. The prevalence of antibacterials (− 4.20 users per 1000 people), antivirals (− 0.04), corticosteroids (− 1.29), prednisolone (− 1.32), calcium channel blocker (− 0.41), and diuretics (− 1.29) was lower than expected after the pandemic’s start, while the prevalence of ivermectin (0.07), sulfonylureas (0.15), sodium-glucose co-transporter-2 (SGLT2) inhibitor (0.17), and anticoagulants (1.95) was higher than expected. The pandemic was associated with statistically significant decreases in the incidence of antibacterials (− 1.21), corticosteroids (− 0.60), prednisolone (− 0.64) and anticoagulants (− 0.02), and increases in ivermectin (0.02), aggregated antidiabetic drugs (0.13), and SGLT2 inhibitors (0.06). These trends were positively associated with pandemic and negatively associated with stringency index.Conclusion: Dispensing of most drugs was not significantly associated with pandemic and government’s response. Despite some statistically significant disruptions, these were not necessarily clinically relevant due to small absolute differences observed.Keywords: COVID-19, drug utilization, repurposed drug, stringency index

Published
2023

3. PI-02: FOLLOW-UP RESULTS OF A PHASE 2 STUDY ASSESSING THE SAFETY AND EFFICACY OF MITAPIVAT TREATMENT, AN ORAL PYRUVATE KINASE ACTIVATOR, FOR UP TO 60 WEEKS IN SUBJECTS WITH SICKLE CELL DISEASE

Author

VAN DIJK M., RAB M., VAN OIRSCHOT B., BOS J., DERICHS C., RIJNEVELD A., CNOSSEN M., NUR E., BIEMOND B., BARTELS M., JANS J., VAN SOLINGE W., SCHUTGENS R., VAN WIJK R., and VAN BEERS E.

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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5. A novel application of Fiber Bragg Grating (FBG) sensors in MPGD

Author

Abbaneo D., Abbas M., Abbrescia M., Abi Akl M., Aboamer O., Acosta D., Ahmad A., Ahmed W., Aleksandrov A., Altieri P., Asawatangtrakuldee C., Aspell P., Assran Y., Awan I., Bally S., Ban Y., Banerjee S., Barashko V., Barria P., Bencze G., Beni N., Benussi L., Bhopatkar V., Bianco S., Bos J., Bouhali O., Braghieri A., Braibant S., Buontempo S., Calabria C., Caponero M., Caputo C., Cassese F., Castaneda A., Cauwenbergh S., Cavallo F.R., Celik A., Choi M., Choi S., Christiansen J., Cimmino A., Colafranceschi S., Colaleo A., Conde Garcia A., Czellar S., Dabrowski M.M., De Lentdecker G., De Oliveira R., de Robertis G., Dildick S., Dorney B., Endroczi G., Errico F., Fenyvesi A., Ferrini M., Ferry S., Furic I., Giacomelli P., Gilmore J., Golovtsov V., Guiducci L., Guilloux F., Gutierrez A., Hadjiiska R.M., Hauser J., Hoepfner K., Hohlmann M., Hoorani H., Iaydjiev P., Jeng Y.G., Kamon T., Karchin P., Korytov A., Krutelyov S., Kumar A., Kim H., Lalli A., Lee J., Lenzi T., Litov L., Loddo F., Madorsky A., Maerschalk T., Maggi M., Magnani A., Mal P.K., Mandal K., Marchioro A., Marinov A., Majumdar N., Merlin J.A., Mitselmakher G., Mohanty A.K., Mohapatra A., Molnar J., Muhammad S., Mukhopadhyay S., Naimuddin M., Nuzzo S., Oliveri E., Pant L.M., Paolucci P., Park I., Passamonti L., Passeggio G., Pavlov B., Philipps B., Piccolo D., Pierluigi D., Postema H., Primavera F., Puig Baranac A., Radi A., Radogna R., Raffone G., Ranieri A., Rashevski G., Riccardi C., Rodozov M., Rodrigues A., Ropelewski L., RoyChowdhury S., Russo A., Ryu G., Ryu M.S., Safonov A., Salva S., Saviano G., Sharma A., Sharma R., Shah A.H., Shopova M., Sturdy J., Sultanov G., Swain S.K., Szillasi Z., Talvitie J., Tatarinov A., Tuuva T., Tytgat M., Valente M., Vai I., Van Stenis M., Venditti R., Verhagen E., Verwilligen P., Vitulo P., Volkov S., Vorobyev A., Wang D., Wang M., Yang U., Yang Y., Yonamine R., Zaganidis N., Zenoni F., and Zhang A.

Subjects
Physics, QC1-999
Abstract

We present a novel application of Fiber Bragg Grating (FBG) sensors in the construction and characterisation of Micro Pattern Gaseous Detector (MPGD), with particular attention to the realisation of the largest triple (Gas electron Multiplier) GEM chambers so far operated, the GE1/1 chambers of the CMS experiment at LHC. The GE1/1 CMS project consists of 144 GEM chambers of about 0.5 m2 active area each, employing three GEM foils per chamber, to be installed in the forward region of the CMS endcap during the long shutdown of LHC in 2108-2019. The large active area of each GE1/1 chamber consists of GEM foils that are mechanically stretched in order to secure their flatness and the consequent uniform performance of the GE1/1 chamber across its whole active surface. So far FBGs have been used in high energy physics mainly as high precision positioning and re-positioning sensors and as low cost, easy to mount, low space consuming temperature sensors. FBGs are also commonly used for very precise strain measurements in material studies. In this work we present a novel use of FBGs as flatness and mechanical tensioning sensors applied to the wide GEM foils of the GE1/1 chambers. A network of FBG sensors have been used to determine the optimal mechanical tension applied and to characterise the mechanical tension that should be applied to the foils. We discuss the results of the test done on a full-sized GE1/1 final prototype, the studies done to fully characterise the GEM material, how this information was used to define a standard assembly procedure and possible future developments.

Published
2018
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6. Quality control for the first large areas of triple-GEM chambers for the CMS endcaps

Author

Abbaneo D., Abbas M., Abbrescia M., Abi Akl M., Aboamer O., Acosta D., Ahmad A., Ahmed W., Aleksandrov A., Altieri P., Asawatangtrakuldee C., Aspell P., Assran Y., Awan I., Bally S., Ban Y., Banerjee S., Barashko V., Barria P., Bencze G., Beni N., Benussi L., Bhopatkar V., Bianco S., Bos J., Bouhali O., Braghieri A., Braibant S., Buontempo S., Calabria C., Caponero M., Caputo C., Cassese F., Castaneda A., Cauwenbergh S., Cavallo F.R., Celik A., Choi M., Choi S., Christiansen J., Cimmino A., Colafranceschi S., Colaleo A., Conde Garcia A., Czellar S., Dabrowski M.M., De Lentdecker G., De Oliveira R., de Robertis G., Dildick S., Dorney B., Endroczi G., Errico F., Fenyvesi A., Ferry S., Furic I., Giacomelli P., Gilmore J., Golovtsov V., Guiducci L., Guilloux F., Gutierrez A., Hadjiiska R.M., Hauser J., Hoepfner K., Hohlmann M., Hoorani H., Iaydjiev P., Jeng Y.G., Kamon T., Karchin P., Korytov A., Krutelyov S., Kumar A., Kim H., Lee J., Lenzi T., Litov L., Loddo F., Madorsky A., Maerschalk T., Maggi M., Magnani A., Mal P.K., Mandal K., Marchioro A., Marinov A., Majumdar N., Merlin J.A., Mitselmakher G., Mohanty A.K., Mohapatra A., Molnar J., Muhammad S., Mukhopadhyay S., Naimuddin M., Nuzzo S., Oliveri E., Pant L.M., Paolucci P., Park I., Passeggio G., Pavlov B., Philipps B., Piccolo D., Postema H., Puig Baranac A., Radi A., Radogna R., Raffone G., Ranieri A., Rashevski G., Riccardi C., Rodozov M., Rodrigues A., Ropelewski L., RoyChowdhury S., Ryu G., Ryu M.S., Safonov A., Salva S., Saviano G., Sharma A., Sharma R., Shah A.H., Shopova M., Sturdy J., Sultanov G., Swain S.K., Szillasi Z., Talvitie J., Tatarinov A., Tuuva T., Tytgat M., Vai I., Van Stenis M., Venditti R., Verhagen E., Verwilligen P., Vitulo P., Volkov S., Vorobyev A., Wang D., Wang M., Yang U., Yang Y., Yonamine R., Zaganidis N., Zenoni F., and Zhang A.

Subjects
Physics, QC1-999
Abstract

The CMS Collaboration plans to equip the very forward muon system with triple-GEM detectors that can withstand the environment of the High-Luminosity LHC. This project is at the final stages of R&D and moving to production. An unprecedented large area of several 100 m2 are to be instrumented with GEM detectors which will be produced in six different sites around the world. A common construction and quality control procedure is required to ensure the performance of each detector. The quality control steps will include optical inspection, cleaning and baking of all materials and parts used to build the detector, leakage current tests of the GEM foils, high voltage tests, gas leak tests of the chambers and monitoring pressure drop vs. time, gain calibration to know the optimal operation region of the detector, gain uniformity tests, and studying the efficiency, noise and tracking performance of the detectors in a cosmic stand using scintillators.

Published
2018
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9. Echocardiographic Diagnosis of Hypertrophic Cardiomyopathy by Machine Learning

Author

Farahani, Nasibeh Zanjirani, Aguirre, Mateo Alzate, Karlinski Vizentin, Vanessa, Enayati, Moein, Bos, J. Martijn, Medina, Andredi Pumarejo, Larson, Kathryn F., Pasupathy, Kalyan S., Scott, Christopher G., Zacher, April L., Schlechtinger, Eduard, Daniels, Bruce K., Kaggal, Vinod C., Geske, Jeffrey B., Pellikka, Patricia A., Oh, Jae K., Ommen, Steve R., Kane, Garvan C., Ackerman, Michael J., and Arruda-Olson, Adelaide M.

Published
2024
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18. Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Author

Bergeman, Auke T., Lieve, Krystien V.V., Kallas, Dania, Bos, J. Martijn, Rosés i Noguer, Ferran, Denjoy, Isabelle, Zorio, Esther, Kammeraad, Janneke A.E., Peltenburg, Puck J., Tobert, Katie, Aiba, Takeshi, Atallah, Joseph, Drago, Fabrizio, Batra, Anjan S., Brugada, Ramon, Borggrefe, Martin, Clur, Sally-Ann B., Cox, Moniek G.P.J., Davis, Andrew, Dhillon, Santokh, Etheridge, Susan P., Fischbach, Peter, Franciosi, Sonia, Haugaa, Kristina, Horie, Minoru, Johnsrude, Christopher, Kane, Austin M., Krause, Ulrich, Kwok, Sit-Yee, LaPage, Martin J., Ohno, Seiko, Probst, Vincent, Roberts, Jason D., Robyns, Tomas, Sacher, Frederic, Semsarian, Christopher, Skinner, Jonathan R., Swan, Heikki, Tavacova, Terezia, Tisma-Dupanovic, Svjetlana, Tfelt-Hansen, Jacob, Yap, Sing-Chien, Kannankeril, Prince J., Leenhardt, Antoine, Till, Janice, Sanatani, Shubhayan, Tanck, Michael W.T., Ackerman, Michael J., Wilde, Arthur A.M., and van der Werf, Christian

Published
2023
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29. Starting Strong: A Randomized Controlled Trial of the Building Assets Reducing Risks (BARR) Model in 9th Grade

Author

Society for Research on Educational Effectiveness (SREE), Hinojosa, T., Bos, J., O'Brien, B., Park, S., Liu, F., and Jerabek, A.

Abstract

Students beginning high school commonly experience increased stress and behavior problems alongside declines in grades, attendance, interest in school, and perceptions of academic competence and self-esteem (Alvidrez & Weinstein, 1993; Reyes et al., 2000). Moreover, research indicates that, relative to students who graduate from high school, those who leave school prematurely are more likely to have experienced deeper 9th grade declines (Reyes et al., 2000; Roderick, 1995). Research also demonstrates positive school climates, positive relationships between students and staff, and among staff, are essential ingredients for turning around low performing schools (Gordon, 2006; National Research Council, 2004; Cohen, 2006; Jerald, 2006; De La Ossa, 2005). More specifically, research is growing on the effectiveness of student-teacher relationships in producing increased attendance and academic performance, and decreased behavior problems. For example, Allen, Pianta, Gregory, Mikami, and Lun (2011) conducted a randomized controlled trial (RCT) in which secondary school teachers were given a year of coaching on effective teaching and student-teacher interactions. After a year of training, students with teachers in the experimental group scored significantly higher on year-end achievement tests than did students in the control group. Quality of student-teacher interaction was a significant mediator of student achievement. With core components derived from research, the Building Assets Reducing Risks (BARR) model© targets students at this critical juncture in their academic career--9th grade. BARR addresses developmental, academic, and structural challenges in the 9th grade by combining student asset building, teachers' real-time analysis of student data, and intensive teacher collaboration to prevent course failure. BARR develops positive student-teacher relationships and integrates student supports into a school's existing model for addressing nonacademic barriers to learning. With funding from the Investing in Innovation program, BARR has been rigorously studied using an RCT and is now under scientific investigation in schools of varying locales and geographic regions to better understand the broader context under which BARR impacts students transitioning to the 9th grade. This current study is a multisite randomized controlled trial that explores replication of BARR across three cohorts of schools. Results from the first RCT demonstrated positive impact on 9th grade students' standardized test scores, credits earned, and overall failure rate. Tables are appended.

Published
2016

36. Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients.

Author

Crotti, Lia, Neves, Raquel, Dagradi, Federica, Musu, Giulia, Giannetti, Federica, Bos, J. Martijn, Barbieri, Miriam, Cerea, Paolo, Giovenzana, Fulvio L. F., Torchio, Margherita, Mura, Manuela, Gnecchi, Massimiliano, Conte, Giulio, Auricchio, Angelo, Sala, Luca, Odening, Katja E., Ackerman, Michael J., and Schwartz, Peter J.

Published
2024
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37. Utilizing median and maximum QTc values improves prediction of breakthrough cardiac events in pediatric long QT syndrome.

Author

Rohatgi, Ram K., Tseng, Andrew S., Sugrue, Alan M., Lee, Alexander T., Scott, Christopher G., Wackel, Phillip L., Cannon, Bryan C., Bos, J. Martijn, and Ackerman, Michael J.

Subjects
LONG QT syndrome treatment, PREDICTIVE tests, RISK assessment, LONG QT syndrome, RESEARCH funding, SYNCOPE, RETROSPECTIVE studies, DESCRIPTIVE statistics, SEIZURES (Medicine), SHOCK (Pathology), CARDIAC arrest, PROGRESSION-free survival, COMPARATIVE studies, ECHOCARDIOGRAPHY, PATIENT aftercare, DISEASE risk factors, CHILDREN
Abstract

Introduction: Although prior studies indicate that a QTc > 500 ms on a single baseline 12‐lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS. Methods: We performed a retrospective analysis of 433 patients with LQTS evaluated, risk‐stratified, and undergoing active guideline‐based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF‐terminating ICD shock, and sudden cardiac death (SCD). Results: During the median follow‐up of 5.5 years (interquartile range [IQR] = 3–9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c‐statistic = 0.93–0.95). Patients in the high‐risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%–81%) when compared to patients in both medium‐risk (93%–97%) and low‐risk (98%–99%) groups. Conclusions: The risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12‐lead ECGs are at the highest risk of BCE while on guideline‐directed medical therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Genotype Predicts Outcomes in Fetuses and Neonates With Severe Congenital Long QT Syndrome

Author

Moore, Jeremy P., Gallotti, Roberto G., Shannon, Kevin M., Bos, J. Martijn, Sadeghi, Elham, Strasburger, Janette F., Wakai, Ronald T., Horigome, Hitoshi, Clur, Sally-Ann, Hill, Allison C., Shah, Maully J., Behere, Shashank, Sarquella-Brugada, Georgia, Czosek, Richard, Etheridge, Susan P., Fischbach, Peter, Kannankeril, Prince J., Motonaga, Kara, Landstrom, Andrew P., Williams, Matthew, Patel, Akash, Dagradi, Federica, Tan, Reina B., Stephenson, Elizabeth, Krishna, Mani Ram, Miyake, Christina Y., Lee, Michelle E., Sanatani, Shubhayan, Balaji, Seshadri, Young, Ming-Lon, Siddiqui, Saad, Schwartz, Peter J., Shivkumar, Kalyanam, and Ackerman, Michael J.

Published
2020
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43. Linking the heart and the brain: Neurodevelopmental disorders in patients with catecholaminergic polymorphic ventricular tachycardia

Author

Lieve, Krystien V.V., Verhagen, Judith M.A., Wei, Jinhong, Bos, J. Martijn, van der Werf, Christian, Rosés i Noguer, Ferran, Mancini, Grazia M.S., Guo, Wenting, Wang, Ruiwu, van den Heuvel, Freek, Frohn-Mulder, Ingrid M.E., Shimizu, Wataru, Nogami, Akihiko, Horigome, Hitoshi, Roberts, Jason D., Leenhardt, Antoine, Crijns, Harry J.G., Blank, Andreas C., Aiba, Takeshi, Wiesfeld, Ans C.P., Blom, Nico A., Sumitomo, Naokata, Till, Jan, Ackerman, Michael J., Chen, S.R. Wayne, van de Laar, Ingrid M.B.H., and Wilde, Arthur A.M.

Published
2019
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44. Proceed with caution: Standard protocol exercise stress tests fail to replicate the diagnostic utility of supine‐stand tests for long QT syndrome.

Author

Pinsky, Alexa M., Kulkarni, Veda K., Bos, J. Martijn, Neves, Raquel, Allison, Thomas G., and Ackerman, Michael J.

Subjects
LONG QT syndrome diagnosis, MEDICAL protocols, RECEIVER operating characteristic curves, DATA analysis, RESEARCH funding, STANDING position, STATISTICAL sampling, RETROSPECTIVE studies, DESCRIPTIVE statistics, ELECTROCARDIOGRAPHY, CARDIOPULMONARY system, SUPINE position, HEART beat, MEDICAL records, ACQUISITION of data, CASE-control method, ONE-way analysis of variance, STATISTICS, EXERCISE tests, DATA analysis software, CONFIDENCE intervals, GENOTYPES, SENSITIVITY & specificity (Statistics)
Abstract

Background: Long QT syndrome (LQTS) is a sudden death predisposing condition characterized by ECG‐derived prolongation of the QT interval. Previous studies have demonstrated that the supine‐stand test may aid in the diagnosis of LQTS as patients fail to shorten their QT interval in response to standing up. The aim of this study was to evaluate the diagnostic accuracy of ECG data derived from standard protocol, clinically performed treadmill exercise stress tests (TESTs) in their ability to mimic the formal supine‐stand test. Methods: We performed a retrospective review of 478 TESTs from patients evaluated for LQTS. Patients referred for evaluation of LQTS but who were dismissed as normal served as controls. Heart rate & QT values were obtained from standard protocol TESTs. Results: Overall, 243 patients with LQTS (125 LQT1, 63 LQT2, 55 LQT3; 146 [60%] female, mean age at TEST 30 ± 17 years) and 235 controls (142 [60%] female, mean age 24 ± 15 years) were included. The paired ΔQTc (QTcStand‐QTcSupine) was similar between LQTS (−5 ± 26) and controls (−2 ± 25; p =.2). During position change, the QT interval shortened by ≥20 ms in 33% of LQTS patients, remained unchanged in 62%, and increased in 5% of LQTS patients which was similar to controls (shortened in 40%, unchanged in 54%, and increased in 6% of controls; p =.2). Receiver‐operator curve analysis to test the diagnostic ability of supine‐stand ΔQT performed poorly in differentiating LQTS from controls with an of AUC 0.52 (p =.4). Conclusion: TESTs should be used with caution when trying to interpret supine‐stand changes for diagnosis of LQTS. [ABSTRACT FROM AUTHOR]

Published
2024
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