Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has changed our lives. The scientific community has been investigating re-purposed treatments to prevent disease progression in coronavirus disease (COVID-19) patients. Objective: To determine whether ivermectin treatment can prevent hospitalization in individuals with early COVID-19. Design, setting and participants: A randomized, double-blind, placebo-controlled study was conducted in non-hospitalized individuals with COVID-19 in Corrientes, Argentina. Patients with SARS-CoV-2 positive nasal swabs were contacted within 48 h by telephone to invite them to participate. The trial randomized 501 patients between August 19th 2020 and February 22nd 2021. Intervention: Patients were randomized to ivermectin (N = 250) or placebo (N = 251) arms in a staggered dose, according to the patient’s weight, for 2 days. Main outcomes and measures: The efficacy of ivermectin to prevent hospitalizations was evaluated as primary outcome. We evaluated secondary outcomes in relationship to safety and other efficacy end points. Results: The mean age was 42 years (SD ± 15.5) and the median time since symptom onset to the inclusion was 4 days [interquartile range 3–6]. The primary outcome of hospitalization was met in 14/250 (5.6%) individuals in ivermectin group and 21/251 (8.4%) in placebo group (odds ratio 0.65; 95% confidence interval, 0.32–1.31; p = 0.227). Time to hospitalization was not statistically different between groups. The mean time from study enrollment to invasive mechanical ventilatory support (MVS) was 5.25 days (SD ± 1.71) in ivermectin group and 10 days (SD ± 2) in placebo group, (p = 0.019). There were no statistically significant differences in the other secondary outcomes including polymerase chain reaction test negativity and safety outcomes. Limitations: Low percentage of hospitalization events, dose of ivermectin and not including only high-risk population. Conclusion: Ivermectin had no significant effect on preventing hospitalization of patients with COVID-19. Patients who received ivermectin required invasive MVS earlier in their treatment. No significant differences were observed in any of the other secondary outcomes. Trial registration: ClinicalTrials.gov NCT04529525.

Objectives: To assess the efficacy of ivermectin in addition to standard treatment compared to standard treatment alone in reducing hospitalizations in the COVID-19 patient population. Trial design: IVERCOR-COVID19 will be a single-center, prospective, randomized, double-blind, parallel group (1:1 ratio), placebo-controlled study. Participants: Patients who meet the following criteria will be invited to participate: Inclusion criteria: (1) Over 18 years of age who reside in the province of Corrientes at the time of diagnosis. (2) Confirmed diagnosis of COVID-19 by polymerase chain reaction (PCR) test for detection of SARS-CoV2 in the last 48 h. (3) In the case of women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study and for the entire period of time for the duration of the study and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study). (4) Weight at the time of inclusion greater than 48 kg. (5) That they sign the informed consent for participation in the study. Exclusion criteria: (1) pregnant or breastfeeding women; (2) known allergy to ivermectin or some of the components of ivermectin tablets or placebo; (3) current use of home oxygen; (4) require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19; (5) presence of mal-absorptive syndrome; (6) presence of any other concomitant acute infectious disease; (7) known history of severe liver disease, for example liver cirrhosis; (8) need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19; (9) need or use of hydroxychloroquine or chloroquine; (10) use of ivermectin up to 7 days prior to randomization; (11) patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months; and (12) current participation or in the last 30 days in a research study that has included the administration of a drug (Table 1). Table 1 Ivermectin/placebo dose according to patient weight Patient weight Ivermectin/placebo dose Total dose (mg) Equal to or greater than 48 kg and less than 80 kg 2 tablets of 6 mg each at the time of inclusion and 2 tablets 24 h after the first intake 24 Equal or greater than 80 kg and less than 110 kg 3 tablets of 6 mg each at the time of inclusion and 3 tablets 24 h after the first intake 36 Equal or greater than 110 kg 4 tablets of 6 mg each at the time of inclusion and 4 tablets 24 h after the first intake 48 The study will be carried out by the Ministry of Public Health of the Province of Corrientes (Argentina) in coordination with the Institute of Cardiology of Corrientes in the Province of Corrientes, Argentina. Intervention and comparator: Intervention group: patients who are randomized to ivermectin will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg ivermectin; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of ivermectin; patients weighing more than 110 kg will receive 4 tablets of 6 mg ivermectin) the day they enter the study and the same dose 24 h after the first dose. Control group: patients who are randomized to placebo will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg placebo; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of placebo; patients weighing more than 110 kg will receive 4 tablets of 6 mg placebo) on the day they enter the study and the same dose 24 h after the first dose (Table 2). Table 2 Inclusion and exclusion criteria Inclusion criteria Exclusion criteria 1. Over 18 years of age who reside in the province of Corrientes at the time of diagnosis 1. Pregnant or breastfeeding women 2.Confirmed diagnosis of COVID-19 by polymerase chain reaction test for detection of SARS-CoV2 in the last 48 h 2. Known allergy to ivermectin or some of the components of ivermectin tablets or placebo 3. In case of being women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study, during the entire period of time for the duration of the study, and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study) 3. Current use of home oxygen 4. Weight at the time of inclusion equal to or greater than 48 kg 4. That require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19 5. That they sign the informed consent for participation in the study 5. Presence of mal-absorptive syndrome 6. Presence of any other concomitant acute infectious disease 7. Known history of severe liver disease, for example liver cirrhosis 8. Need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19 9. Need or use of hydroxychloroquine or chloroquine 10. Use of ivermectin up to 7 days prior to randomization 11. Patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months 12. Current participation or in the last 30 days in a research study that has included the administration of a drug Main outcomes: Primary outcome will be the percentage of hospitalizations in patients with COVID-19 in the intervention and control groups. Secondary outcomes: time to hospitalization in each of the arms of the study: number of days elapsed from the inclusion in the study until the hospitalization of the patient; percentage of use of invasive mechanical ventilation in each of the study arms: every patient who is connected to invasive mechanical ventilation after signing the informed consent and before the final study visit; time to invasive mechanical ventilation in each of the arms of the study: number of days elapsed from inclusion in the study to connection to invasive mechanical ventilation of the patient; percentage of patients requiring dialysis in each of the study arms: all patients who require renal replacement therapy of any kind, temporary or permanent, and which begins after signing the informed consent and before the final visit; mortality from all causes in each of the two trial groups: death of the patient, from any cause. Negative PCR swab at 3 ± 1 and 12 ± 2 days after entering the study. Ivermectin safety: it will be analyzed according to the incidence of adverse events that patients present in the intervention and control groups. The end of study (EOS) is recorded as the day the patient is discharged or death. Discharge will be granted according to the current recommendations of the Ministry of Public Health of the Province of Corrientes. A follow-up visit (EOF) will be made by phone 30 days after the EOS when vital status will be verified. Randomization: Randomization will be done through a web system with randomly permuted blocks. Randomization will be carried out by one of the investigators who will not participate in the inclusion of patients or in the delivery of medication (Table 3). Table 3 EOS end of study, EOF end of follow-up Visit Basal and randomization, day 0 Day 3 ± 1 Day 12 ± 2 V#1 V#2 V#3 EOS EOF Informed consent X – – – – Inclusion/exclusion criteria X – – – – Demographic data and medical history X – – – – Concomitant medication X – – – – Vital signs* X X – – – Anthropometric data^{^} X – – – – Basal laboratory X – – – – PCR swab – X X – – Assessment of adverse events – X X X – Final objective evaluation – X X X X Randomization X – – – – Adherence to treatment X X – – – *Includes heart rate, temperature, and oxygen saturation by a digital saturometer ^Includes weight and height Blinding (masking): The participants, investigators, care providers, and outcome assessors will be blinded. Numbers to be randomized (sample size): We will include a total of 500 patients (250 patients in each group). Trial status: This is version 1.0, 17 August 2020. The recruitment started on 19 August 2020, and we anticipate the trial will finish recruitment on 31 December 2020. Trial registration: ClinicalTrials.gov NCT04529525. Registered on 26 August 2020 Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Modelling of patient-specific hemodynamics for a clinical case of severe coronary artery disease with the bifurcation stenosis was carried out with allowance for standard angiographic data obtained before and after successfully performed myocardial revascularization by stenting of two arteries. Based on a non-Newtonian fluid model and an original algorithm for fluid dynamics computation operated with a limited amount of initial data, key characteristics of blood flow were determined to analyse the features of coronary disease and the consequences of its treatment. The results of hemodynamic modelling near bifurcation sites are presented with an emphasis on physical, physiological and clinical phenomena to demonstrate the feasibility of the proposed approach. The main limitations and ways to minimize them are the subjects of discussion as well. This article is part of the theme issue ‘Transport phenomena in complex systems (part 2)’.

Цель. Выявить и оценить взаимосвязи между смертностью населения в Тюменской области и числом ЧКВ при ОКС в этом регионе в период с 2006 по 2012гг.Материал и методы. Использованы данные о количестве ЧКВ, представленные в ежегодных информационно-аналитических сборниках “Сердечно-сосудистая хирургия. Болезни и врожденные аномалии системы кровообращения”. Данные о смертности и заболеваемости опубликованы в статистических материалах департамента здравоохранения Тюменской области. Результаты. За изучаемый период на юге Тюменской области отмечалось прогрессивное снижение смертности населения и значительно увеличилось количество ЧКВ при ОКС. Была выявлена обратная корреляционная связь между количеством ЧКВ при ОКС и показателями общей смертности населения (r= –0,857, р=0,014), общей смертности среди трудоспособного населения (r= –0,893, р=0,007) и смертности населения от ССЗ (r= –0,857, р=0,014). Количество ЧКВ, выполняемых при ИМ оказалось связанным с общей смертностью (r= –0,929, p=0,003), общей смертностью среди трудоспособного населения (r= –0,964; р<0,001), смертностью от ИМ среди трудоспособного населения (r= –0,893; р=0,007) и среди мужчин трудоспособного населения (r= –0,893; р=0,007). Заключение. Наши данные подтверждают, что снижение сердечно-сосудистой смертности населения в Тюменской области во многом обусловлено прогрессивным увеличением с 2006 по 2012гг числа ЧКВ при острых формах ИБС.

Aim      To evaluate the effect of the total time of myocardial ischemia on results of the treatment of patients with ST segment elevation acute myocardial infarction (STEMI) who underwent percutaneous coronary interventions (PCI). Material and methods This study used data from a hospital register for PCI in STEMI from 2006 through 2017. 1649 patients were included. Group 1 consisted of 604 (36.6 %) patients with a total time of myocardial ischemia not exceeding 1880 min; group 2 included 531 (32.2 %) patients with a duration of myocardial ischemia from 180 to 360 min; and group 3 included 514 (31.2 %) patients with a duration of myocardial ischemia longer than 360 min. Results Mortality was lower in group 1 (2.3 %) than in groups 2 and 3 (6.2 and 7.2 %, respectively; p1–2=0.001; p1–3<0.001; p2–3=0.520). The incidence of major cardiac complications (“adverse cardiac events”, MACE) was lower in group 1 (4.1 %) than in groups 2 and 3 (7.3 and 9.5 %, respectively, p _1–2 =0.020; p _1–3 180 min were age (odd ratio, OR, 1.01 at 95 % confidence interval, CI, 1.0 to 1.02; р=0.044), female gender (OR, 1.64 at 95 % CI 1.26 to 2.13; р<0.001), chronic kidney disease (OR 1.82 at 95 % CI 1.21 to 2.74; р=0.004). Performing prehospital thrombolysis was associated with a decrease in the total time of myocardial ischemia (OR 0.4 at 95 % CI 0.31 to 0.51; р<0.001). A strong direct correlation was observed between the total time of myocardial ischemia and the time from the onset of pain syndrome to hospitalization (r=0.759; р180 min was associated with increased mortality and development of MACE. The total time of myocardial ischemia > 360 min was associated with increased incidence of the no-reflow phenomenon. The major predictors for the time of myocardial ischemia >180 min included age, female gender, and chronic kidney disease. The use of pharmacoinvasive strategy was associated with an increased number of patients with a total duration of myocardial ischemia <180 min. The contribution of the time of prehospital delay to the total time of myocardial ischemia was greater than the contribution of the “door-to-balloon” time. The time of prehospital delay showed a strong direct correlation with the total time of myocardial ischemia.

This mainly theoretical work is devoted to the study of the contribution of the cell-free layer (CFL) near the vessel wall to hemodynamics in a large coronary artery with stenosis to assess the relevance of CFL modeling to the needs of interventional cardiology. An Euler–Euler model considering blood as a two-component fluid with a discrete phase of erythrocytes and a liquid plasma phase was applied to a simple 2d vessel with 65% stenosis. It was found that both the CFL thickness and the local contribution of the CFL thickness to hemodynamics are inhomogeneous along the vessel. The effects of CFL on the velocity profiles, vortex formation, hematocrit, viscosity, and wall shear stresses in the area of stenosis were determined. To demonstrate the significance of CFL modeling for prognostic purposes, the same hemodynamic conditions, analyzed using a one-component model, were also considered. A comparison analysis showed that the existence of CFL resulted in a significant overestimation (up to over 100%) of the main hemodynamic characteristics of the flow obtained using the model based on the Carreau equation.