Use of Living Systematic Reviews (LSRS) Beyond COVID-19

Objectives: A LSR is a systematic review that is continually updated, incorporating new evidence as it becomes available. They are conducted in research areas where new evidence is constantly emerging on diagnostic methods, treatments, and outcomes. The objective of this study was to understand the current application of LSRs across research areas. Method(s): Embase, MEDLINE, and the Cochrane Database of Systematic Reviews were searched to identify LSRs. Only the most recent update of a LSR was included. Data regarding the indication, intervention, methods, frequency of updates, and funding were extracted. Result(s): Of the 1,243 records identified, 126 LSRs were included for analysis. The first LSR was published in 2015, with a significant increase in the number of LSRs published starting in 2020, coinciding with the COVID-19 pandemic. The most common indication represented by LSRs was COVID-19 (72%), followed by oncology (10%). Other indications with LSRs included chronic pain, traumatic brain injury, and skin disorders, among others. While most oncology LSRs identified interventional randomized-controlled trials (RCTs) (85%), only 54% of COVID-19 LSRs were restricted to interventional studies, including a combination of RCTS and real-world observational studies. Oncology LSRs included common cancers such as prostate, renal, or multiple myeloma. Of the reviews that reported update frequency, 28% planned monthly, 12% yearly, and 12% weekly updates. Only 46% of LSRs were registered. The majority of LSRs were funded by government or research organizations. Objectives of LSRs varied, with most stating the need to maintain up-to-date databases;however, several studies used LSRs to facilitate network meta-analysis or mixed treatment comparisons. Conclusion(s): While LSRs were introduced over five years ago, their frequency increased during the COVID-19 pandemic. Apart from COVID-19, LSRs are commonly used in oncology settings. LSRs provide high-level, relevant, and up-to-date evidence, making them a useful tool for clinical and real-world research.Copyright © 2023

Isometric thumb extension exercise as part of a multimodal intervention for de Quervain's syndrome: A randomised feasibility trial

Introduction: de Quervain's syndrome is a painful condition commonly presented to hand therapists. Exercise is utilised as an intervention, but isometric exercise has not been investigated. We aimed to assess the feasibility and safety of isometric thumb extension exercise for de Quervain's syndrome and to explore differences between high-load and low-load isometric exercise. Method(s): This parallel-group randomised clinical feasibility trial included individuals with de Quervain's syndrome. All participants underwent a 2 week washout period where they received an orthosis, education, and range of motion exercises. Eligible participants were then randomised to receive high or low-load isometric thumb extension exercises, performed daily for 4 weeks. Feasibility and safety were assessed by recruitment and drop-out rates, adherence, adverse events, and participant feedback via semi-structured interviews. Secondary outcomes included patient-reported outcomes for pain and function, and blinded assessment of range of motion and strength. Result(s): Twenty-eight participants were randomised. There were no drop-outs after randomisation, and no serious adverse events. Adherence to exercise was 86.7%, with 84% of participants stating they would choose to participate again. There were clinically and statistically significant improvements in pain and function over time (p < 0.001) but not in range of motion or strength. There were no statistically significant between-group differences. Conclusion(s): Isometric thumb extension exercise within a multimodal approach appears a safe and feasible intervention for people with de Quervain's syndrome. A large multi-centre trial would be required to compare high- and low-load isometric exercises. Further research investigating exercise and multimodal interventions in this population is warranted.Copyright © The Author(s) 2023.

Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.

INTRODUCTION: Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil. METHODS: We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré. RESULTS: Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset. CONCLUSION: An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.

Performance of two educational approaches in increasing knowledge of high-school students about COVID-19 during the first wave of pandemic.

OBJECTIVES: The coronavirus disease (COVID-19) pandemic has greatly altered peoples' daily lives. Teachers and students were found quite unprepared for the emergence of the first COVID-19 wave. So, improving the knowledge of students about COVID-19 is an important issue. METHODS: In this study, 240 high students attended. Two interventions with the same contents, but in different ways, were delivered. A structured questionnaire was utilized to collect data on demographic information, and information about the behavioral intention toward COVID-19 before and after the educational interventions as well as a control group that received no educational intervention. RESULTS: students in all arms had similar baseline knowledge of COVID-19. The results of the post-analysis showed the efficiency of educational techniques in increasing students' knowledge about COVID-19. So the audio-visual training method performed significantly better than the visual training method (p = 0.03). Both approaches achieved better scores than the control group (P < 0.001). CONCLUSION: During the outbreak of COVID-19, multimedia-based learning is a more effective educational approach and can improve the learning outcomes related to COVID-19 and achieve learning goals without close contact than written materials.

Effect of folic acid in patients with lung damage caused by coronavirus SARS-CoV-2

Aim of study. To evaluate the influence exerted by additional use of a fixed combination of folic acid with pyridoxine hydrochloride and cyanocobalamin in complex therapy for hospitalised patients with COVID-19-associated lung damage on parameters of inflammation and clinical outcomes. Material and methods. A comparative prospective interventional study included 117 patients with a lung lesion volume caused by the SARS-CoV-2 coronavi-rus corresponding to CT-1 and CT-2. The study group included 78 patients who additionally received a fixed combination of 5mg folic acid, 4mg pyridoxine hydrochloride, and 6mug cyanocobalamin three times a day in combination with standard therapy. The comparison group included 39 patients. Results. By days 14-21 of hospitalisation, the main group showed a decrease in the proportion of patients with CT symptoms of "cobblestone appearance" by 26% (p = 0.005) and an increase in the proportion of patients with transformation of viral lung lesions into areas of consolidation of the pulmonary parenchyma by 23% (p <0.001). The effect of a fixed combination of folic acid with vitamins B6, B12 on the achievement of the level of C-reactive protein <20 mg / l by day 7 depending on the red blood parameters and the number of platelets was established (likelihood ratio test in the logistic regression model: 13.925;P = 0.084) as well as the shortening of the time period required to reach the first negative result of the SARS-CoV-2 RNA test (in the linear regression model, R = 0.437;R2 = 0.191;F = 4.552;p = 0.006). Conclusion. The use of a fixed combination of folic acid with vitamins B6, B12 for patients with COVID-19 is associated with earlier achievement of positive dynamics in CT symptoms of lung damage. The additional use of these micronutrients in combination with restoration of red blood count and platelet count improves the odds ratio of an early decrease in serum C-reactive protein, negative result of the SARS-CoV-2 RNA test.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

Procalcitonin combined to point of care molecular respiratory panel testing for antibiotic stewardship in the emergency room: the PROARRAY study

Introduction: Molecular syndromic respiratory panel (RP) or procalcitonin (PCT)-driven algorithms have reported conflicting efficacy for antibiotic ATB) stewardship in LRTI. We hypothesized that combining real-time PCT measurement and virus identification would reduce ATB exposition in LRTI suspicions presenting to the emergency department (ED). Method(s): PROARRAY study is a prospective, randomized interventional trial, conducted in the adult ED of an academic 1600-bed hospital. Patients attending the ED with a suspicion of LRTI were randomized into the intervention arm (systematic PCT measurement and point of care BIOFIRE RP2plus (then 2.1) testing, with the recommendation to withhold or withdraw ATB if PCT < 0.25 mug/L and/or identification of a virus) or a standard of care (SOC) arm. The primary endpoint was the duration of antibiotic exposure in the first 28 days. Result(s): 451 patients were randomized (intervention: 225, SOC: 226), mean age 62.5 +/- 19.4 years, hospitalization rate 59.9%, mean length of stay 7.4 +/- 8.4 days. Main diagnoses were CAP (n = 129), COVID-19 (n = 91), AECOPD (n = 31). The BIOFIRE RP2.1plus identified at least one viral species in 112 patients (49.8%). The duration of ATB exposition in ITT population was 6.00 [0.00;9.00] and 5.00 [0.00-9.00] days in the SOC and interventional arm respectively (p = 0.71). ATB was started in 31.3% and 34.1% respectively (p = 0.54). ATB exposure was below 6 days in 100 (47.2%) and 108 patients (50.59%) respectively (p = 0.58). Conclusion(s): Displaying real-time PCT and RP results failed to significantly reduce the ATB exposition in LRTI suspicions. However, the ATB duration and rate of initiation were already low in SOC arm, which comprised PCT measurement in routine in our ED. Routine PCT measurement probably participated to the lower median ATB duration (6.0 days) than hypothesized (9.0 days) and argues for the main contribution of PCT in ATB stewardship. Moreover, as the intervention was done at ED's level, we did not control for ATB stewardship in wards for inpatients.

Which biomarker(s) to predict worsening of SARS-CoV2 infection? An ancillary study from the COVIDeF cohort

Introduction: COVID-19 has been responsible for millions of deaths and intensive care unit (ICU) admissions all over the world. Identifying the patients at risk of developing a severe form is crucial for an optimized orientation and allocation of resources. The main objective of our study was to identify among a selection of biomarkers, those predictive of short term worsening in COVID-19. Method(s): This is an ancillary study using clinical data and collected biobanking from the multicentric cohort study COVIDeF, which included prospectively from March 31th 2020 to March 30th 2021, patients admitted with a suspected Sars-CoV2 infection in the Assistance- Publique-Hopitaux de Paris network, France. Patients with confirmed COVID-19 were divided in 2 groups: a severe (ICU admission or invasive or non-invasive ventilation or ARDS or death) and a control group (no worsening). The routine blood tests and following biomarkers: troponin, C Reactive Protein (CRP), procalcitonin, Mild- Regional pro-Adrenomedulin (MR-proADM), pro-endothelin, SuPAR, NT-proBNP, calprotectin, PF4, D-dimers, were measured in plasma or serum and compared between both groups using a conditional logistic regression. Result(s): Among the 1040 first patients included in the COVIDEF cohort, we selected 512 patients having a blood sample drawn at admission before worsening, of which 60 secondarily worsened (severe group). The mean age was 59.5 (+/- 19.5) years and 50.2% were females. Among the biomarkers tested, three were independently associated with worsening: CRP (mg/l) OR 1.01 [IC 1.01-1.02], procalcitonin (ng/ml) OR 0.4428 [0.21-0.95] and MR-proADM (pg/ml) OR 3.012 [1.06-8.53]. Conclusion(s): Among a selection of biomarkers of interest, MRproADM appears to best identify at admission COVID-19 patients at risk of worsening. Future interventional studies should test the efficacy and security of this biomarker to rule-in and rule-out severe outcome and the usefulness for allocating resources.

FAVIPIRAVIR IN THE TREATMENT OF MILD CORONAVIRUS INFECTION: RESULTS OF A MULTICENTER OPEN-LABEL, POST-REGISTRATION, NON-INTERVENTIONAL STUDY.

Clinical parameters characterizing the efficacy and safety of favipiravir were examined in a multicenter, non-interventional (before-and-after study design) trial in 264 patients with mild COVID-19. It is shown that on the background of 14-day therapy with favipiravir body temperature normalized, blood oxygen saturation improved, and the frequency of tachycardia detection reduced by 16% (p < 0.0001). A statistically significant decrease by 91,3% (p 0.0001) in the frequency of SARS-nCoV-2 RNA detection in the nasopharyngeal mucosa discharge was revealed. A decrease in the concentration of ferritin (by 69% compared to initial values), blood glucose (by 21%), creatinine (by 10%), C-reactive protein (by 36%) (p 0.0001), and D-dimer by 61% (p = 0.016) was noted. The results of the SF-36 health survey questionnaire revealed a significant (p 0.05) improvement in the quality of life in terms of physical functioning (by 35%), and role functioning associated with physical and emotional state by 107% and 160%, respectively. Analysis of the COV19-QoL questionnaire revealed a decrease by 24% in negative perception of the disease (p < 0,01). Among the identified adverse events, elevated level of ALT (in 39.47% of patients), hyperuricemia (in 28.95% of patients), and elevated AST (in 23.68% of patients) prevailed. All the adverse events occurred with mild or moderate severity. There were no lethal outcomes in the studied sample of patients. The analysis showed a satisfactory level of the tolerability of the treatment.Copyright © 2023 Izdatel'stvo Meditsina. All rights reserved.

Characteristics Of Heart Failure Clinical Trials Registered In Clinicaltrials.gov- A Cross Sectional Analysis

Purpose: To perform an analysis of trends and characteristics of heart failure (HF) trials registered in ClinicalTrials.gov (CTG). Design(s): Cross-sectional study Methods: All heart failure clinical trials registered on CTG from September 27, 2007 to March 31, 2022 were identified using Advanced Search feature in ClinicalTrials.gov. Trial characteristics were assessed through relative frequency calculations. Hazard ratio and 95% confidence intervals were determined for characteristics associated with early discontinuation. Result(s): A total of 4272 clinical trials were registered in CTG during this period. There were 68.8% interventional studies and 31.2% were observational studies. Patient registry studies constituted 15.8% of observational studies. Interestingly, registry studies in HF were more frequent compared overall clinical studies (4.8% vs 2.5%). In HF, 32.4% trials were funded by industry, 6.6% trials were by funded the National Institute of Health (NIH) and other U.S Federal agencies (FA) and 61.8% trials by all others which includes individuals, universities, research organizations etc. Observational studies constituted 28% of the industry sponsored trials in HF versus 15% of the total registered clinical trials. Completion rate were 58.9% for NIH and FA funded trials as compared to 50% for industry sponsored and 38.9% for other sponsored. Discontinuation rates were 9.6% for NIH and FA funded trials as compared to 16.8% for industry sponsored. On the other hand unknown status of the trial was higher for other sponsors (19.8%) as compared to NIH and FA (3.2%) and industry sponsors (9.3%). Trend analysis for last 15 years showed an increasing number of clinical trials in HF each year. During the two years of COVID-19 pandemic (April 2020 to March 2022) 15.5% total number of trials registered were in HF even though the number of NIH and FA funded trials decreased by 28.9%. This was much higher than the previous two years (April 2018 to March 2020). Total of 492 trials (11.52%) were withdrawn, suspended or discontinued early. Trials were less likely to be discontinued if funded by sources other than industry and NIH considered together (OR 1.93;X2= 47.50;p<0.01). A detailed analysis of various phases of trials and trends of discontinued trials will also be presented. Conclusion(s): Number of clinical trials in HF are increasing. Registry trials and observational studies are more common in HF. Number of HF trials increased during COVID-19 pandemic. Trials funded by NIH and FA have better completion rate, whereas discontinuation rates were much higher for industry sponsored trials.Copyright © 2022

Fear of covid-19, stress and coping strategies among nurses during the covid-19 pandemic's second wave: A quasi-intervention study

Background: The COVID-19 pandemic and its related consequences caused a higher risk of mental health problems for nurses. Hence, this study aims to reduce the level of fear and stress related to the COVID-19 pandemic and promote active coping among Egyptian nurses. Method(s): This quasi-intervention study was conducted on 125 nurses working at Benha's University hospitals, who were selected by a systematic random sampling technique within the time interval of March 2021 to July 2021. The study was conducted using the fear of COVID-19 scale, the stress scale of depression, anxiety and stress scales, and the Brief (COPE) inventory scale. Result(s): The mean ages of the studied nurses were 36.70 +/- 9.50. Almost half of the studied nurses were males and married. Before the intervention, 47.2% of nurses had severe stress levels while 82.4% had a high level of fear of COVID-19. Experience years, type of department, and worries about vaccine side effects were the predictors of the fear of COVID-19. A significant difference (p =.000) was found between both mean stress and fear scores pre-intervention (15.27 +/- 5.47 and 25.56 +/- 6.13) and post-intervention (4.87 +/- 2.14 and 11.92 +/- 2.43). The most prevalent coping strategies among nurses before the intervention were self-distraction (5.03 +/- 1.53), followed by behavioral disengagement and self-blaming. However, after the intervention, religion was found to be the utmost coping mechanism (6.12 +/- 1.17), followed by positive reframing and acceptance. Conclusion(s): The majority of the nurses in the study reported a significant fear of COVID-19, and around half of the nurses had severe stress as a result. After the intervention, the stress and fear scores were reduced by half or even less. Age, longer work experience, and worries about the vaccine were the predictors of fear of COVID-19. The coping strategies used after the intervention shifted toward active coping strategies.Copyright © 2023 Omar et al.

TrialTree: A Novel Application for Interactive Trial Design

Background: Important lapses in the research enterprise, notably low-quality studies, amount to research waste. Close to 50% of this research waste comes from research on low-priority research questions, omitting important outcomes, not involving stakeholders in research design and poor methodology. With the COVID-19 pandemic, the urge to generate evidence to address important questions regarding optimal management strategies has further aggravated this problem. Most COVID-related trials are of low quality. This is in part due to deficiencies in designing high-quality trials at short notice. Consequently, results from these trials do not reliably inform clinical practice for the treatment or management of patients with COVID-19. Innovative approaches to trial design that incorporate existing tools are required to ensure that trials can be designed rapidly, efficiently, and consistently. Learning objectives: (1) To understand the key features of trial design. (2) To apply the use of existing trial resources in trial design. (3) To learn about how to match the research question with the appropriate design features. (4) To be able to use an electronic application to design a trial. Outline: In the first part, participants will review core concepts in trial design (equipoise, research question formulation, knowledge gaps, hypotheses etc.) and a collection of tools/frameworks meant to enhance trial design. These tools/frameworks include the PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2), Template for Intervention Description and Replication (TIDieR), Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), Core Outcome Measures in Effectiveness Trials (COMET;https://comet-initiative.org/), TrialForge (Tools aimed at improving trial efficiency;https:// www.trialforge.org/), Support for statistical analyses plans (SAP), PROGRESS-Plus (a framework of sociodemographic factors-Place of residence, Race/ethnicity/ culture/language, Occupation, Gender/Sex, Religion, Education, Socioeconomic status, and Social capital-'Plus' refers to other personal, time-dependent or relationship-dependent factors, such as pregnancy, age, disability, and sexual orientation). The second part will be a hands-on session in trial design using the TrialTree application (https://trialtree.logicnets.net/ lmc/TT) and the production of a design report. TrialTree is organized into eight modules that cover the main design features. It includes tips, prompts, and feedback on trial design. Evaluation: (1) Completion of a post-workshop quiz. (2) Production of a complete design report in TrialTree. Materials required: (1) A laptop (access to the TrialTree application will be provided free of charge). (2) Pre-workshop readings will be provided. Goals of Session: The goal of this session is to build capacity in novice and experienced trialists on the use of an electronic application for interactive trial design.

Simultaneous Individual Complicated Grief Treatment With a Couple

Persistent complex bereavement/complicated grief occurs when, after a period of 12 months following a death, there remains an ongoing intense yearning and sorrow for the deceased, preoccupation with the death and its circumstances, difficulty accepting its reality, and disruption in personal identity. This case study illustrates the successful application of Complicated Grief Treatment (CGT), a manualized research-supported intervention, with a husband and wife each receiving individual therapy simultaneously with separate clinicians. The core of CGT involves graded completion of imaginal and situational revisiting (i.e., exposure) exercises. To target maladaptive rumination and counterfactual thinking more explicitly, strategies from a research-based treatment for trauma, Cognitive Processing Therapy, were also incorporated for one member of the couple. To our knowledge, CGT has not been examined with couples receiving individual therapy delivered simultaneously. As such, practitioners have little information about how to proceed with cases where multiple members of the same family are experiencing complicated grief. We will detail the treatment provided, outlining the course of care for each member of the couple, highlighting unique adjustments made to tailor implementation to each individual and to deliver the intervention simultaneously. Quantitative and qualitative data show the effects of treatment on symptoms of complicated grief, depression, and relationship satisfaction.Copyright © The Author(s) 2022.

From 2020 Home BP Consensus to 2022 TSOC/THS Hypertension Guideline

Background: Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Numerous epidemiological studies and pharmacological intervention trials have demonstrated that lower and lowering blood pressures (BP) are associated with fewer CV events and lower mortality. Despite the positive correlations between BP levels and later CV events are continuous since BP levels as low as 90/60 mmHg in almost all large-scale epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years (since the release of the Fifth Report of the Joint National Committee [JNC 5] on high BP in 1993). The publication of both the SPRINT and the STEP trials (comprising >8,500 Caucasian/African and Chinese participants, respectively) provides enough evidence to shake this 140/90 mmHg dogma. In both trials, lowering systolic BP (SBP) to <130 mmHg, compared to the traditional SBP target of <140 (130-139) mmHg, was consistently associated with a 25-30% relative risk reduction in CV events. Another dogma regarding hypertension management is "office (or clinic) BP measurements" Although standardized office BP measurement has been widely recommended, the practice of office BP measurements is hard to be or has never been ideal in real-world practice. Further, the debate regarding the numerical equivalence between automated office BP (AOBP) measurements adopted in the SPRINT trial and office BP measurements has never been settled. The variations of office BP readings and the differences between office BP and home BP readings bewilder not only patients, but also healthcare professionals. On the other hand, out-of-office BP monitoring receives growing attention in contemporary hypertension guidelines. Home BP monitoring (HBPM) and ambulatory BP monitoring (ABPM) are two recognized approaches to obtaining out-of-office BP. HBPM is easy-to-use, more likely to be free of environmental and/or emotional stress (such as white-coat effect), feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events. Methods/Results: The Taiwan Hypertension Society (THS) and the Taiwan Society of Cardiology (TSOC) jointly issued the Consensus Statement on HBPM in 2020. The "722" protocol to standardize HBPM has been advocated by both Societies and widely accepted by healthcare professionals. In the 2022 Taiwan Hypertension Guidelines, we break the dogma of "office BP-based management strategy" and further expand the role of HBPM to the whole hypertension management process, from diagnosis to long-term follow-up. The Task Force considers that, to improve the quality of long-term management of all chronic diseases including hypertension, patients themselves should take an active role and HBPM is the right tool to achieve this goal, regardless of many other advantages of HBPM. This approach is of particularly importance in the post-COVID era and can bridge the management with artificial intelligence technologies. Conclusion(s): To facilitate implementation of the guidelines, a series of flowcharts to encompass assessment, adjustment, and HBPM-guided hypertension management are provided.

Future of Arterial Stiffness Measurement, Clinical Applications

Arterial stiffness is the best surrogate for vascular aging. We have put forward the notion of early vascular aging (EVA), in which subjects have arteries older than chronological age. On the opposite, subjects can be resilient to the effect of age and risk factors, and present arteries younger than chronological age, called supernormal vascular aging (SUPERNOVA). In the present lecture, I will discuss the definition and clinical utility of EVA and SUPERNOVA, how we can practically measure EVA and SUPERNOVA in clinics, and what measures can be applied to correct for EVA, and promote SUPERNOVA, especially in the context of COVID pandemic. I will also present the first results from the SPARTE interventional trial, and what the next steps should be.

SAFETY AND EFFICIENCY OF INHALATION METHOD FOR ADMINISTRATION OF SMALL EXTRACELLULAR VESICLES DERIVED FROM MULTIPOTENT MESENCHYMAL STROMAL CELLS OF HUMAN UMBILICAL CORD IN SARS-COV-2 ASSOCIATED PNEUMONIA.

The coronavirus infection (COVID-19), an acute viral disease with predominant affection of the upper respiratory tract, is a challenge for modern medicine. Considering the fact that in the patho-genesis of coronavirus pneumonia there is violation of the im-mune response (hyper-response, cytokine storm) the drugs that locally regulate it may be promising in the pneumonia treatment. Biological activity of exosomes is widely investigated in the world. Small extracellular vesicles of mesenchymal cells have the following effects: anti-apoptotic, proliferation stimulation, anti-inflammatory and immunomodulatory. Objective(s): to evaluate the safety and efficacy of the method of inhalation administration of small extracellular vesicles in bilateral pneumonia caused by a new SARS-CoV-2 coronavirus infection. To study these effects an interventional, prospective, random-ized, double-blind, placebo-controlled study has been conducted to evaluate the safety and efficacy of inhaled small extracellular vesicles administration to the patients with bilateral pneumonia caused by the new coronavirus infection SARS-CoV-2. Altogether 36 patients with confirmed new coronavirus infection COVID-19, complicated by bilateral pneumonia of moderate severity (12 patients each in study groups 1 and 2, depending on the type of given small extracellular vesicles, and the control group) participated in the study. Small extracellular vesicles were inhaled twice a day in the dose of 2-10x1010 particles. The efficacy and safety of the method were assessed judging by the patients' general state, as-sessment of the disease severity, general and biochemical blood tests, coagulogram, saturation, CT scan of the lungs before and after 10 days of treatment. The observation period was 30 days after hospitalization. During the study the safety of the method was proved, all the patients recovered. Reliable differences of the blood CRP index, which normalized by day 10 of treatment in groups 1 and 2, but remained elevated in the control group. No significant differences were found in other assessed parameters.Copyright © 2022, Human Stem Cell Institute. All rights reserved.

Interventions for improving indoor and outdoor air quality in and around schools

Students spend nearly one third of their typical day in the school environment, where they may be exposed to harmful air pollutants. A consolidated knowledge base of interventions to reduce this exposure is required for making informed decisions on their implementation and wider uptake. We attempt to fill this knowledge gap by synthesising the existing scientific literature on different school-based air pollution exposure interventions, their efficiency, suitability, and limitations. We assessed technological (air purifiers, HVAC - Heating Ventilation and Air Conditioning etc.), behavioural, physical barriers, structural, school-commute and policy and regulatory interventions. Studies suggest that the removal efficiency of air purifiers for PM2.5, PM10, PM1 and BC can be up to 57 %, 34 %, 70 % and 58 %, respectively, depending on the air purification technology compared with control levels in classroom. The HVAC system combined with high efficiency filters has BC, PM10 and PM2.5 removal efficiency up to 97 %, 34 % and 30 %, respectively. Citizen science campaigns are effective in reducing the indoor air pollutants' exposure up to 94 %. The concentration of PM10, NO2, O3, BC and PNC can be reduced by up to 60 %, 59 %, 16 %, 63 % and 77 %, respectively as compared to control conditions, by installing green infrastructure (GI) as a physical barrier. School commute interventions can reduce NO2 concentration by up to 23 %. The in-cabin concentration reduction of up to 77 % for PM2.5, 43 % for PNC, 89 % for BC, 74 % for PM10 and 75 % for NO2, along with 94 % reduction in tailpipe emission of total particles, can be achieved using clean fuels and retrofits. No stand-alone method is found as the absolute solution for controlling pollutants exposure, their combined application can be effective in most of the scenarios. More research is needed on assessing combined interventions, and their operational synchronisation for getting the optimum results.Copyright © 2022 The Authors

Evaluating the Effectiveness of Interventions to Improve the Follow-up Rate for Children With Visual Disabilities in an Eye Hospital in Nepal: Nonrandomized Study.

BACKGROUND: Monitoring ocular morbidity among pediatric patients requires regular follow-up visits. We found that the follow-up rate was poor among children in our setting. Therefore, we intended to assess the effectiveness of 2 interventions-(1) counseling and (2) SMS text messaging and phone calls-to improve the follow-up rates. OBJECTIVE: This study aimed to evaluate the effectiveness of 2 interventions, counseling and SMS and phone calls group, as well as a routine standard care for improving the follow-up rate of pediatric patients. METHODS: A Nonrandomized, quasiexperimental design was used. Children (aged 0-16 years) with ocular conditions requiring at least 3 follow-up visits during the study period were included. A total of 264 participants were equally allocated to the 3 intervention groups of (1) counseling, (2) SMS and phone calls, and (3) routine standard care group. A 20-minute counseling session by a trained counselor with the provision of disease-specific leaflets were given to those in the counseling group. For the second intervention group, parents of children received an SMS text 3 days before and a phone call 1 day before their scheduled follow-up visits. Participants allocated for the routine standard care group were provided with the existing services with no additional counseling and reminders. Participants attending 3 follow-ups within 2 days of the scheduled visit date were considered compliant. The difference in and among the proportion of participants completing all 3 follow-up visits in each group was assessed. RESULTS: The demographic characteristics of the participants were similar across the study groups. Only 3% (8/264) of participants completed all 3 follow-up visits, but overall compliance with the follow-up, as defined by the investigators, was found to be only 0.76% (2/264). There was no statistically significant difference in the proportion of follow-up between the intervention groups. However, the proportion of participants attending the first and second follow-ups, as well as the overall total number of follow-ups, was more in the SMS and phone-call group followed by the counseling group. CONCLUSIONS: We did not find any evidence on the effectiveness of our interventions to improve the follow-up rate. The primary reason could be that this study was conducted during the COVID-19 pandemic. It could also be possible that the intensity of the interventions may have influenced the outcomes. A rigorously designed study during the absence of any lockdown restrictions is warranted to evaluate intervention effectiveness. The study also provides useful insights and highlights the importance of designing and systematically developing interventions for improving the follow-up rate and ensuring a continuum of care to children with visual disabilities in Nepal and similar contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT04837534; https://clinicaltrials.gov/ct2/show/NCT04837534. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/31578.

Recruitment of Adolescent Young Carers to a Psychosocial Support Intervention Study in Six European Countries: Lessons Learned from the ME-WE Project.

Young carers provide a substantial amount of care to family members and support to friends, yet their situation has not been actively addressed in research and policy in many European countries or indeed globally. Awareness of their situation by professionals and among children and young carers themselves remains low overall. Thus, young carers remain a largely hidden group within society. This study reports and analyses the recruitment process in a multi-centre intervention study offering psychosocial support to adolescent young carers (AYCs) aged 15-17 years. A cluster-randomised controlled trial was designed, with recruitment taking place in Italy, the Netherlands, Slovenia, Sweden, Switzerland and the United Kingdom exploiting various channels, including partnerships with schools, health and social services and carers organisations. In total, 478 AYCs were recruited and, after screening failures, withdrawals and initial dropouts, 217 were enrolled and started the intervention. Challenges encountered in reaching, recruiting and retaining AYCs included low levels of awareness among AYCs, a low willingness to participate in study activities, uncertainty about the prevalence of AYCs, a limited school capacity to support the recruitment; COVID-19 spreading in 2020-2021 and related restrictions. Based on this experience, recommendations are put forward for how to better engage AYCs in research.

Menstrual Irregularities Post-COVID-19 Infection/Vaccination in Indian Population

Introduction: Increased reporting of menstrual disturbances post-vaccination and inadequate inclusion of questions about menstruation in vaccine trials and disease progression studies have been the baseline for conducting this study. We aim to assess the influence of vaccines and COVID-19 infection on menstruation and identify patterns, if any, in cycles post-disease/vaccination. Methods: A multicenter observational study was performed using a questionnaire-based survey via an online link. The participants who filled the survey were predominantly in the age group of 21–25 years (80%). Participants with prior menstrual irregularities were eliminated from the study. Results: The prevalence of unusual menstrual cycles post-infection/vaccination was 21.7%. A total of 17.11% experienced changes post-vaccination and 22.8% of the infected individuals reported abnormalities post-COVID-19 disease. A substantial increase in dysmenorrhea was reported (p <0.001) post-infection/vaccination. An increase in menstrual flow was observed in 14.9% post-vaccination and 23.9% post-infection. Conclusion: Menstrual changes post-vaccination were insignificant;however, significant differences in menstruation were reported post-infection. The study strengthens the association between COVID-19 and menstruation and urges the inclusion of menstrual health in disease intervention studies.