One or two doses of live varicella virus-containing vaccines: Efficacy, persistence of immune responses, and safety six years after administration in healthy children during their second year of life

Abstract Background This phase III B follow-up of an initial multicenter study (NCT00226499) will evaluate the ten-year efficacy of two doses of the combined measles-mumps-rubella-varicella vaccine (MMRV) and one dose of the live attenuated varicella vaccine (V) versus a measles-mumps-rubella control group (MMR) for the prevention of clinical varicella disease. Here we present efficacy results for six years post-vaccination. Methods In phase A of the study, healthy children aged 12–22 months from ten European countries were randomized (3:3:1) and received either two doses of MMRV, or one dose of combined MMR and one dose of monovalent varicella vaccine (MMR+V), or two doses of the MMR vaccine (control), 42 days apart. Vaccine efficacy against all and against moderate or severe varicella (confirmed by detection of viral DNA or epidemiological link) was assessed from six weeks up to six years post-dose 2 for the MMRV and MMR+V groups, and was calculated with 95% confidence intervals (CI). The severity of varicella was calculated using the modified Vazquez scale (mild ≤ 7; moderately severe = 8–15; severe ≥ 16). Herpes zoster cases were also recorded. Results 5289 children (MMRV = 2279, mean age = 14.2, standard deviation [SD] = 2.5; MMR+V = 2266, mean age = 14.2, SD = 2.4; MMR = 744, mean age = 14.2, SD = 2.5 months) were included in the efficacy cohort. 815 varicella cases were confirmed. Efficacy of two doses of MMRV against all and against moderate or severe varicella was 95.0% (95% CI: 93.6–96.2) and 99.0% (95% CI: 97.7–99.6), respectively. Efficacy of one dose of varicella vaccine against all and against moderate or severe varicella was 67.0% (95% CI: 61.8–71.4) and 90.3% (95% CI: 86.9–92.8), respectively. There were four confirmed herpes zoster cases (MMR+V = 2, MMR = 2), all were mild and three tested positive for the wild-type virus. Conclusions Two doses of the MMRV vaccine and one dose of the varicella vaccine remain efficacious through six years post-vaccination

corrigendum to one or two doses of live varicella virus containing vaccines efficacy persistence of immune responses and safety six years after administration in healthy children during their second year of life vaccine 36 2018 381 387

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Фармакологическая безопасность при беременности: систематический обзор применения потенциально тератогенных лекарственных средств

Objective: To assess the prevalence of potentially teratogenic drug utilization by pregnant women: overall and in the periconceptional period. Methods: The electronic database PubMed/Medline was searched for the following keywords: «pharmacoepidemiology», «pregnancy», «drug use», «safety», «pregnancy risk category», «fetal risk», «teratogen». The systematic analysis included 28 studies published in English from January 2006 to 23 December 2015. Results. The review shows that the study designs and the choices for data analysis and presentation of results differ largely across published studies. In the USA and Canada, measured rates of maternal use of contraindicated drugs (FDA category X) during pregnancy ranged from 2.4% to 5.3% (1.1–5.0% in the first trimester).The use of drugs with positive evidence of risk (FDA category D) ranged from 5.8% to 39.6% (2.7–6.0%). In European countries, proportions of women using drugs of risk categories X and D ranged from 1.0% to 4.9% (0.31–3.2%) and from 2.0% to 5.9% (1.6–3.7%), respectively. In developing countries, respective proportions of women ranged within 0.2–2.1% and 1.9–11.4%. In early pregnancy (the first trimester), the proportion of women taking potentially teratogenic drugs was high if compared with the second and third trimesters. The use of contraindicated drugs during pregnancy fastly decreases compared with the period before conception. Although the reduction of use of drugs with positive evidence of risk is less marked, possibly, with relation of their efficacy for the treatment of chronic conditions. On the base of analyzed studies, the reference list of potentially teratogenic drugs was formed. Conclusion. The results of published literature confirm differences in study methods that make it difficult to compare the application of potentially teratogenic drugs in pregnancy. The fundamental challenge remains an insufficiency or lack of available information on the evidence of risk to fetus cuased by the drugs that are most widely used in pregnancy.Цель исследования: оценить распространенность использования потенциально тератогенных лекарственных средств (ЛС) женщинами на протяжении всей беременности и в периконцептуальном периоде. Методы. Поиск проводился в электронной базе данных Medline (PubMed) с использованием ключевых слов «pharmacoepidemiology», «pregnancy», «drug use», «safety», «pregnancy risk category», «fetal risk», «teratogen». В систематический обзор включали результаты исследований, опубликованных на английском языке в период с января 2006 по декабрь 2015 г. Результаты. Проанализированы результаты 28 исследований. Показано, что в США и Канаде доля беременных, принимавших противопоказанные препараты (категория X по классификации FDA), варьировала от 2,4 до 5,3% (1,1–5,0% в I триместре), а с доказанным риском (категория D) — от 5,8 до 39,6% (2,7–6,0). В европейских странах доля беременных, принимавших препараты категории X, варьировала в пределах 1,0–4,9% (0,3–3,2), препараты категории D — 2,0–5,9% (1,6–3,7), в развивающихся странах — в пределах 0,2–2,1 и 1,9–11,4% соответственно. Доля женщин, принимавших потенциально тератогенный препарат в I триместре, была выше по сравнению с величиной показателя во II и III триместрах. С наступлением беременности по сравнению с периодом до зачатия использование противопоказанных ЛС быстро уменьшается. Однако редукция в применении препаратов с доказанным риском менее выражена, возможно, из-за большей их востребованности для лечения хронических состояний. На основании полученных сведений сформирован рекомендательный перечень потенциально тератогенных ЛС. Заключение. Опубликованные данные подтверждают различия в методах исследования, затрудняющие сравнение оценки использования ЛС во время беременности. Фундаментальной проблемой остается недостаточность или отсутствие доступной информации о фетальной безопасности ЛС, часто используемых при беременности.

Federation Pharmacological Safety in Pregnancy: Modern Knowledge, Practice and Pharmacoepidemiological Approaches to the Studying and Recognizing of Drugs with Teratogenic Risk

One of the key issues in obstetric practice remains the lack or incompleteness of information on the teratogenicity of most drugs used by pregnant women. Uncertainty regarding teratogenic risks significantly affect the quality of information on drugs; nevertheless, counseling patients allows arriving at a more balanced solution regarding their risk in pregnancy. Determination of the most commonly taken drugs (prescription or OTC) in the first trimester of gestation and increase of knowledge on their embryofetal risks optimizes pharmacotherapy during pregnancy. Characteristics and epidemiological analysis of possible factors, including drugs, associated with the occurrence of congenital anomalies, are crucial for the development of prevention activities that have an impact on the incidence of defects

Pharmacological Safety in Pregnancy: A Systematic Review On the Use of Potentially Teratogenic Drugs

Objective: To assess the prevalence of potentially teratogenic drug utilization by pregnant women: overall and in the periconceptional period. Methods: The electronic database PubMed/Medline was searched for the following keywords: «pharmacoepidemiology», «pregnancy», «drug use», «safety», «pregnancy risk category», «fetal risk», «teratogen». The systematic analysis included 28 studies published in English from January 2006 to 23 December 2015. Results. The review shows that the study designs and the choices for data analysis and presentation of results differ largely across published studies. In the USA and Canada, measured rates of maternal use of contraindicated drugs (FDA category X) during pregnancy ranged from 2.4% to 5.3% (1.1–5.0% in the first trimester).The use of drugs with positive evidence of risk (FDA category D) ranged from 5.8% to 39.6% (2.7–6.0%). In European countries, proportions of women using drugs of risk categories X and D ranged from 1.0% to 4.9% (0.31–3.2%) and from 2.0% to 5.9% (1.6–3.7%), respectively. In developing countries, respective proportions of women ranged within 0.2–2.1% and 1.9–11.4%. In early pregnancy (the first trimester), the proportion of women taking potentially teratogenic drugs was high if compared with the second and third trimesters. The use of contraindicated drugs during pregnancy fastly decreases compared with the period before conception. Although the reduction of use of drugs with positive evidence of risk is less marked, possibly, with relation of their efficacy for the treatment of chronic conditions. On the base of analyzed studies, the reference list of potentially teratogenic drugs was formed. Conclusion. The results of published literature confirm differences in study methods that make it difficult to compare the application of potentially teratogenic drugs in pregnancy. The fundamental challenge remains an insufficiency or lack of available information on the evidence of risk to fetus cuased by the drugs that are most widely used in pregnancy

Antimicrobial Dispensing Practice in Community Pharmacies in Russia during the COVID-19 Pandemic

COVID-19 has had a significant impact on health care systems, including drug use. The present study aimed to evaluate the patterns of community supply of antimicrobials from community pharmacies during the COVID-19 pandemic in five cities of Russia. In a cross-sectional study, a random sample of pharmacies reported all episodes of antimicrobials supply during a one-week period. Patterns of supply (age and gender of customer, drug name and formulation, prescription availability, indication, etc.) were analyzed. Altogether, 71 pharmacies took part in the study and 5270 encounters were recorded. In total, 4.2% of visits resulted in supply of more than one antimicrobial agent and 5.2% were for parenteral formulations. The rate of prescription-based purchase in participated cities varied from 40.5 to 99.1%. Systemic antibiotics and antivirals accounted for the majority of supplies (60.5 and 26.3%, respectively). Upper respiratory tract infections were reported as the indication for antimicrobials usage in 36.9% of cases, followed by skin and soft tissue infections (12.1%) and urinary tract infections (8.7%); COVID-19 accounted for 8.4% of all supplies. Amoxicillin with clavulanic acid, azithromycin and amoxicillin were indicated as the top three antimicrobials purchased for upper respiratory tract infections, and azithromycin, umifenovir and levofloxacin were the top three for COVID-19. In general, a high rate of drugs dispensing without prescription was revealed. Antibiotics for systemic use remained the most common antimicrobials, whereas presumably viral upper respiratory tract infections were the main reason for their purchase. COVID-19 infection itself was responsible for a small proportion of the supply of antimicrobial agents, but systemic antibiotics accounted for more than a half of supplies

Antimicrobial prescribing patterns in patients with COVID-19 in Russian multi-field hospitals in 2021 : results of the Global-PPS Project

The COVID-19 pandemic is a global public health challenge with understudied effects on antimicrobial usage. We aimed to analyze antimicrobial prescribing patterns in COVID-19 patients in Russian multi-field hospitals by means of the Global-PPS Project developed by the University of Antwerp. Out of 999 patients in COVID-19 wards in six hospitals surveyed in 2021, 51.3% received antimicrobials (79% in intensive care, 47.5% in medical wards). Systemic antivirals and antibiotics were prescribed to 31% and 35.1% of patients, respectively, and a combination of both to 14.1% of patients. The top antivirals administered were favipiravir (65%), remdesivir (19.2%), and umifenovir (15.8%); the top antibiotics were ceftriaxone (29.7%), levofloxacin (18%), and cefoperazone/sulbactam (10.4%). The vast majority of antibiotics was prescribed for treatment of pneumonia or COVID-19 infection (59.3% and 25.1%, respectively). Treatment was based on biomarker data in 42.7% of patients but was targeted only in 29.6% (6.7% for antibiotics). The rate of non-compliance with guidelines reached 16.6%. Antimicrobial prescribing patterns varied considerably in COVID-19 wards in Russian hospitals with groundlessly high rates of systemic antibiotics. Antimicrobial usage surveillance and stewardship should be applied to inpatient care during the COVID-19 pandemic

A randomized trial assessing the efficacy, immunogenicity, and safety of vaccination with live attenuated varicella zoster virus-containing vaccines: ten-year follow-up in Russian children

In Russia, a universal varicella vaccination (UVV) program has not been implemented, and varicella vaccination coverage is low. We assessed the efficacy, antibody persistence, and safety of one- and two-dose varicella vaccination schedules in Russian children with a ten-year follow-up period, as part of an international phase IIIB, observer-blind, randomized, controlled trial (NCT00226499). Children aged 12–22 months were randomized (3:3:1) to receive two doses of tetravalent measles-mumps-rubella-varicella vaccine (V2 group), one dose trivalent measles-mumps-rubella (MMR) vaccine and one dose of varicella vaccine (V1 group), or two doses of MMR vaccine (V0 [control] group), 42 days apart. Main study outcomes were: vaccine efficacy (VE) against confirmed varicella cases, anti-varicella zoster virus (VZV) seropositivity rates and geometric mean concentrations, and reporting of (serious) adverse events ([S]AEs). The total vaccinated cohort in Russia comprised 1000 children; 900 were followed up until study end (year [Y] 10). VE estimates against confirmed varicella (Y10) were 92.4% in the V2 group and 74.7% in the V1 group. Anti-VZV seropositivity rates remained ≥99.4% in the V2 group and ≥89.7% in the V1 group from day 42 post-vaccination 2 until Y10. Occurrence of (un)solicited AEs and SAEs was similar across groups and confirmed the safety profile of the vaccines. No vaccination-related SAEs or deaths were reported. These results are consistent with the global trial results, i.e., the highest VE estimates observed following the two-dose schedule compared to the one-dose schedule. These data may inform decision-making related to potential implementation of a UVV program

Antimicrobial Prescribing Patterns in Patients with COVID-19 in Russian Multi-Field Hospitals in 2021: Results of the Global-PPS Project

The COVID-19 pandemic is a global public health challenge with understudied effects on antimicrobial usage. We aimed to analyze antimicrobial prescribing patterns in COVID-19 patients in Russian multi-field hospitals by means of the Global-PPS Project developed by the University of Antwerp. Out of 999 patients in COVID-19 wards in six hospitals surveyed in 2021, 51.3% received antimicrobials (79% in intensive care, 47.5% in medical wards). Systemic antivirals and antibiotics were prescribed to 31% and 35.1% of patients, respectively, and a combination of both to 14.1% of patients. The top antivirals administered were favipiravir (65%), remdesivir (19.2%), and umifenovir (15.8%); the top antibiotics were ceftriaxone (29.7%), levofloxacin (18%), and cefoperazone/sulbactam (10.4%). The vast majority of antibiotics was prescribed for treatment of pneumonia or COVID-19 infection (59.3% and 25.1%, respectively). Treatment was based on biomarker data in 42.7% of patients but was targeted only in 29.6% (6.7% for antibiotics). The rate of non-compliance with guidelines reached 16.6%. Antimicrobial prescribing patterns varied considerably in COVID-19 wards in Russian hospitals with groundlessly high rates of systemic antibiotics. Antimicrobial usage surveillance and stewardship should be applied to inpatient care during the COVID-19 pandemic