Waning Effectiveness of SARS-CoV-2 mRNA Vaccines in Older Adults: A Rapid Review

The U.S. Centers for Disease Control and Prevention (CDC) and other health agencies have recently recommended a booster dose of COVID-19 vaccines for specific vulnerable groups including adults 65 years and older. There is limited evidence whether vaccine effectiveness in older adults decreases over time, especially against severe COVID-19. We performed a rapid review of published studies available through 04 November 2021 that provide effectiveness data on mRNA vaccines approved/licensed in the United States and identified eight eligible studies which evaluated vaccine effectiveness in older adults. There is evidence of a decline in vaccine effectiveness against both SARS-CoV-2 infection and severe COVID-19 in older adults among studies which analyzed data up to July-October 2021. Our findings suggest that vaccine effectiveness diminishes in older adults, which supports the current recommendation for a booster dose in this population.

Neutralization of SARS-CoV-2 Omicron pseudovirus by BNT162b2 vaccine-elicited human sera

A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage, B.1.1.529, was recently detected in Botswana and South Africa and is now circulating globally. Just two days after it was first reported to the World Health Organization (WHO), this strain was classified as a variant of concern (VOC) and named Omicron. Omicron has an unusually large number of mutations, including up to 39 amino acid modifications in the spike (S) protein, raising concerns that its recognition by neutralizing antibodies from convalescent and vaccinated individuals may be severely compromised. In this study, we tested pseudoviruses carrying the SARS-CoV-2 spike glycoproteins of either the Wuhan reference strain, the Beta, the Delta or the Omicron variants of concern with sera of 51 participants that received two doses or a third dose (≥6 months after dose 2) of the mRNA-based COVID-19 vaccine BNT162b2. Immune sera from individuals who received two doses of BNT162b2 had more than 22-fold reduced neutralizing titers against the Omicron as compared to the Wuhan pseudovirus. One month after a third dose of BNT162b2, the neutralization titer against Omicron was increased 23-fold compared to two doses and antibody titers were similar to those observed against the Wuhan pseudovirus after two doses of BNT162b2. These data suggest that a third dose of BNT162b2 may protect against Omicron-mediated COVID-19, but further analyses of longer-term antibody persistence and real-world effectiveness data are needed.

Development of Student Worksheets Based on a Multi-Representation Approach to Improve Students' Mastery of Sound Wave Concepts

This development research aims to produce a product in the form of student worksheets based on a multi-representation approach to improve students' mastery of the sound wave concept that is valid, and effective. The product developed is student worksheets. The research design used is a 4D model consisting of Define, Design, Develop and Disseminate. Data collection techniques used validation sheets and concept mastery evaluation tools. Device validity data were analyzed using a Likert scale. Product effectiveness data were analyzed using Gain standards. Product validity was assessed by three expert validators and three practitioner validators. The assessment by the expert validator is 3.50 and by the practitioner validator it is 3.70 with valid criteria. The average result of the N Gain test for mastery of Sound Wave concepts is 0.73 in the high category. So, it can be concluded that student worksheets based on a multi-representation approach to improve students' mastery of sound wave concepts are valid and effective

PENGEMBANGAN MODUL PEMBELAJARAN FISIKA SMA POKOK BAHASAN FLUIDA STATIS BERBASIS POTENSI LOKAL PADA WADUK LECARI BANYUWANGI

ABSTRAKBerdasarkan survei awal yang dilakukan di SMAN 1 Gambiran, media pembelajaran di kelas menggunakan buku ajar konvensional. Beberapa penelitian pada buku ajar menunjukkan adanya miskonsepsi pada penjelasan konsep, penyajian rumus, penulisan simbol, penggunaan satuan, penyajian gambar maupun penyajian soal. Modul merupakan salah satu sarana selain buku ajar yang dapat membantu siswa dalam menghubungkan materi pada kehidupan sehari-hari, susunan modul juga tidak hanya materi saja namun modul juga menyajikan contoh soal, ringkasan, latihan soal, dan tes formatif. Modul dapat digunakan secara mandiri dalam mencapai tujuan pembelajaran, sehingga siswa mampu berkembang dengan sendirinya. Pengimplementasian potensi lokal pada sarana pembelajaran juga layak dikembangkan dan memudahkan siswa untuk memahami materi yang terdapat dalam modul. Penelitian ini menggunakan model pengembangan four-D, analisis data yang digunakan terbagi menjadi tiga, yaitu validitas, kepraktisan, dan efektivitas. Teknik analisis data untuk validitas menggunakan analisis deskriptif kuantitatif. Pada efektivitas menggunakan ketuntasan individu dan ketuntasan belajar klasikal. Sedangkan untuk kepraktisan menggunakan analisis skala Likert lima interval secara kuantitatif. Hasil validasi menunjukkan klasifikasi sangat valid dan dapat digunakan sebagai bahan ajar. Hasil respon siswa mendapatkan persentase 75,6% dengan kriteria praktis. Hasil efektivitas diperoleh dari ketuntasan belajar klasikal yang mencapai 86,67% dengan kriteria sangat baik. Modul pengembangan dinyatakan valid, praktis dan efektif. Kata kunci: modul; potensi lokal; validitas; kepraktisan; efektivitas. ABSTRACTBased on the initial survey conducted at SMAN 1 Gambiran, the learning media in the classroom uses conventional textbooks. Several studies on textbooks show that there are misconceptions in explaining concepts, presenting formulas, writing symbols, using units, presenting images and presenting questions. The module is a tool other than textbooks that can help students relate material to everyday life. The module arrangement is not only material but also provides sample questions, summaries, practice questions, and formative tests. Modules can be used independently in achieving learning objectives, so that students are able to develop on their own. The implementation of local potential in learning facilities is also worth developing and making it easier for students to understand the material contained in the module. This study uses a four-D development model, the data analysis used is divided into three, namely validity, practicality, and effectiveness. Data analysis techniques for validity using quantitative descriptive analysis. On the effectiveness of using individual mastery and classical learning completeness. As for the practicality of using a Likert scale analysis of five intervals quantitatively. The validation results show the classification is very valid and can be used as teaching materials. The results of student responses get a percentage of 75.6% with practical criteria. The results of the effectiveness obtained from classical learning completeness which reached 86.67% with very good criteria. The development module is declared valid, practical and effective. Keywords: module; local potencial; validity; practicality; effectiveness.

Safety and Effectiveness of Idelalisib in Patients with Double-Refractory Follicular Lymphoma: A Pan-European Cohort of 242 Patients

Background: Malignant lymphoid cells are characteristically dependent on signals mediated by the phosphatidylinositol 3-kinase delta isoform (PI3Kδ). Idelalisib is an oral, selective, PI3Kδ inhibitor approved by the FDA and EMA as monotherapy for the treatment of advanced follicular lymphoma (FL). The approval was based on a phase 2 trial in patients with indolent non-Hodgkin lymphoma including 72 patients with FL who were refractory to at least 2 prior regimens (NCT01282424; Study 101-09). Interim safety analysis of this large, pan-European, noninterventional study of refractory FL patients treated with idelalisib monotherapy (EUPAS19618; NCT03568929) showed that the adverse event (AE) profile in clinical practice corroborates the known safety profile of idelalisib reported from clinical trials. Herein, we report the effectiveness and updated safety analysis from this study. Methods: This was a non-interventional, retrospective, cohort study. Adult patients treated with idelalisib for FL in routine clinical practice in 10 European countries were included. Data were collected retrospectively from sites by study personnel from remotely source data-verified medical records using electronic case report forms. Safety and effectiveness data for each patient were collected from time of idelalisib initiation until 6 months post-discontinuation of idelalisib, start of next treatment, or death. For this analysis, the data cut-off date was 16 June 2021. Effectiveness of idelalisib was assessed by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). The overall safety profile of idelalisib was assessed by estimating the incidence of AEs, serious AEs, adverse drug reactions (ADRs), and serious ADRs. Focus was given to special health outcomes of interest (HOIs), including transaminase elevation, hepatocellular injury, severe diarrhea/colitis, pneumonitis, neutropenia, rash, Stevens-Johnson syndrome, and serious infections. Multivariate Poisson regression analyses are used to estimate rates of ADRs, serious ADRs, and HOIs, and are adjusted for potential confounders. Time-to-event data were analyzed using Kaplan-Meier methods. Results: Overall, there were 257 eligible patients in the study from 85 sites. The Full Analysis Set (FAS) consisted of 242 patients excluding those with deviations (n=10) or those without any data contribution at the cut-off date (n=5). Of the 242 patients, 183 initiated idelalisib at least 12 months prior to data cut-off date and were included in the Effectiveness Analysis Set (EAS; n=49 patients did not have effectiveness data recorded, and 10 did not meet effectiveness inclusion criteria). For the 183 patients in the EAS, median age was 67 years and 54.6% (n=100) were male (Fig. 1A). Median number of prior therapies was 3 (range 1-10) and median time since diagnosis was 5.8 years (range: 0.4-32). At treatment initiation, 64% (n=117) had Ann Arbor stage III/IV disease. Median duration of idelalisib exposure was 6.8 months (IQR 3.0-15.6); 41.5% (n=76) had dose interruptions. Patients received doses of 150 mg only (67.8%), both 150 mg and 100 mg (28.4%), or 100 mg only (3.8%). Patients were observed for a median of 9.8 months (IQR 5.2-19.3). In the EAS, 103/183 patients achieved a response with 30 patients (16.4%) achieving a complete response (CR) and 73 (39.9%) achieving a partial response (PR), yielding a best ORR of 56.3% (95% CI: 48.8-63.6; Fig. 1B). Median DOR, PFS, and TTNT were 22.5 (95% CI: 15.1-27.9), 11.1 (95% CI: 8.1-18.1) and 15.4 months (95% CI: 9.9-22.2), respectively (Fig. 1B, C). Median OS had not been reached at the time of data cut-off (Fig. 1D). Updated safety information was available from the 242 patients in the FAS. The most frequent AEs recorded were infections, diarrhea and/or colitis, and transaminase elevation. The proportion of patients in the FAS experiencing Grade 3/4, severe, common, and HOI TEAEs are presented in Fig. 1E. Conclusions: We report to our knowledge the largest cohort of FL patients treated with idelalisib outside of the clinical trial setting. Our effectiveness findings are remarkably similar to those from the registrational study 101-09 (Gopal 2014 N Engl J Med). Safety profile of idelalisib was consistent with trial experience, and no new safety signals were identified. Idelalisib remains an effective treatment option for FL patients. Figure 1 Figure 1. Disclosures Gyan: Gilead Sciences, Inc.: Consultancy; Novartis: Research Funding; Mundipharma: Research Funding; Fresenius Kabi: Research Funding; Sanofi: Honoraria; AbbVie: Other: Hospitality; AstraZeneca: Honoraria. Tisi: Incyte: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Merli: Takeda: Consultancy; Janssen Pharmaceuticals: Consultancy; Gilead Sciences, Inc.: Consultancy; Novartis: Consultancy. Di Raimondo: Amgen: Honoraria; AbbVie: Honoraria; Pfizer: Honoraria; Bristol Myers Squibb: Honoraria; Janssen Pharmaceuticals: Honoraria; Jazz Pharmaceutical: Honoraria. Mercadal: Gilead Sciences, Inc.: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Vandenberghe: Janssen Pharmaceuticals: Honoraria; AbbVie: Honoraria. Boland: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Shah Gupta: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. van Troostenburg: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Dunnill: Gilead Sciences, Inc.: Current equity holder in publicly-traded company, Other: Contractor. Ramroth: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Rajakumaraswamy: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Salles: Genentech/Roche: Consultancy; Incyte: Consultancy; Regeneron: Consultancy, Honoraria; Miltneiy: Consultancy; Genmab: Consultancy; Epizyme: Consultancy, Honoraria; Velosbio: Consultancy; Novartis: Consultancy; Ipsen: Consultancy; Morphosys: Consultancy, Honoraria; Allogene: Consultancy; Debiopharm: Consultancy; Janssen: Consultancy; Kite/Gilead: Consultancy; Loxo: Consultancy; Takeda: Consultancy; Rapt: Consultancy; BMS/Celgene: Consultancy; Beigene: Consultancy; Abbvie: Consultancy, Honoraria; Bayer: Honoraria.

PENGEMBANGAN EMORISH UNTUK MENINGKATKAN KETERAMPILAN PEMECAHAN MASALAH PADA PEMBELAJARAN FISIKA

Penelitian ini bertujuan menghasilkan produk berupa EMORISH yang layak digunakan dalam pembelajaran Fisika untuk meningkatkan keterampilan pemecahan masalah peserta didik. Jenis penelitian yang digunakan adalah penelitian dan pengembangan melalui model ADDIE dengan desain uji coba one group pre-test post-test design. Subjek uji coba pada penelitian ini ialah 25 orang peserta didik kelas X program MIPA SMAN 6 Banjarmasin. Penilaian mengenai kelayakan produk yang dikembangkan ditinjau berdasarkan tiga aspek yang meliputi validitas, kepraktisan, dan efektivitas. Teknik pengumpulan data diperoleh melalui instrumen tes dan non-tes. Instrumen non-tes meliputi penilaian validator untuk mengukur validitas EMORISH dan angket respon peserta didik untuk mengukur kepraktisan EMORISH. Sementara instrumen tes meliputi penilaian hasil belajar peserta didik saat pre-test dan post-test untuk mengukur efektivitas EMORISH. Analisis data diperoleh melalui rata-rata uji validitas, rata-rata skor angket respon peserta didik, dan uji N-gain pada tes hasil belajar. Hasil penelitian menunjukkan bahwa EMORISH berkategori sangat valid dengan skor 3,54, EMORISH berkategori praktis dengan skor 2,86, EMORISH dinyatakan efektif berdasarkan perolehan n-gain dengan skor 0,37 dan berkategori sedang, sehingga EMORISH layak digunakan dalam proses pembelajaran untuk meningkatkan keterampilan pemecahan masalah peserta didik.THE DEVELOPMENT OF EMORISH TO IMPROVE STUDENTS’ PROBLEM-SOLVING SKILLS IN PHYSICS LEARNING This research aims to produce EMORISH (electronic module on simple harmonic motion subject) which is eligible to be implemented in physics learning process to improve students' problem solving skills. This research used research and development through the ADDIE model within a one group pre-test post-test design. The research subjects in this study were 25 students X grade of MIPA program at Senior High School 6 Banjarmasin. The assessment of the eligibility of the product is based on three aspects including validity, practicality, and effectiveness. Data collection techniques were obtained through test and non-test instruments. Non-test instruments include validator assessments to measure EMORISH validity and student response questionnaires to measure EMORISH practicality. Meanwhile, the test instrument is student learning outcomes during pre-test and post-test to measure EMORISH effectiveness. Data analysis was obtained through the average validity test, students' questionnaire responses average score, and the N-gain score on learning outcomes test. The research showed that EMORISH was in the very valid category with a score of 3.54, EMORISH was in the practical category with a score of 2.86, EMORISH was declared effective based on the acquisition of n-gain with a score of 0.37 and was in the moderate category, so that EMORISH was eligible to be implemented in physics learning process to improve students' problem solving skills.

14. Postmarketing Safety Experience With MenACWY-TT

Background MenACWY-TT (Nimenrix®), a quadrivalent meningococcal tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in 82 countries but not in the United States. MenACWY-TT is administered in infants as a 2 + 1 (6 weeks to < 6 months of age) or 1 + 1 (6 to < 12 months of age) schedule with the booster dose at 12 months of age, and from 12 months of age as a single dose. In addition to its widespread use to protect against meningococcal serogroups A, C, W, and Y, MenACWY-TT is a constituent of an investigational pentavalent meningococcal (MenABCWY) vaccine currently undergoing clinical development. Methods Using the MenACWY-TT Periodic Safety Update Report (PSUR) with format and content in accordance with Good Pharmacovigilance Practice Module VII and International Council for Harmonisation Guideline E2C, for data up to April 19, 2020, postmarketing safety experience with MenACWY-TT is considered. The PSUR data included herein are spontaneous adverse events (AEs) from the Pfizer safety database. AEs were coded by system organ class (SOC) and preferred term (PT) using MedDRA v.22.1J. Results The cumulative estimated exposure of MenACWY-TT was nearly 26 million doses, with the majority administered in 0- to 16-year-olds and in the Western European Union (Figure 1). Over the reporting period, 13,301 cumulative AEs occurred. The most common SOCs in the reporting period were general disorders and administration site conditions (n=5169; 39%); nervous system disorders (n=1986; 15%); injury, poisoning and procedural complications (n=1266; 10%); and gastrointestinal disorders (n=1031; 8%) (Figure 2). By PT, the most common AEs were pyrexia (n=1613; 12%), headache (n=738; 6%), and vaccination site pain (n=394; 3%) (Figure 3). Of the 3299 serious AEs reported, the most common were pyrexia (n=317; 10%) and headache (n=209; 6%). Conclusion Based on cumulative safety data in conjunction with existing efficacy and effectiveness data, the benefit-risk profile of MenACWY-TT remains favorable and is consistent with the safety profile of MenACWY-TT established in clinical studies. Disclosures Lidia Serra, MS, Pfizer Inc (Employee, Shareholder) Susan Mather, MD, Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Chris Webber, MD, Pfizer (Employee, Shareholder)

Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.