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Background: Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities. Methods: The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023. Discussion: This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS. Trial registration: ClinicalTrials.gov NCT03800524. Registered on January 11, 2019. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a pandemic of unprecedented proportions in recent human history. To date, the world has paid a high toll in terms of human lives lost, and on economic, financial, and social repercussions. In Europe, countries tried to mobilize all resources available to contain the COVID-19 effects, but the outcomes are diverse across countries. There have also been massive efforts geared towards finding safe and effective vaccines and to distribute them massively to the population. The main objective of this paper is to describe the COVID-19 prevalence in Europe. Secondly, it aims to identify epidemiological typologies allowing to distinguish the countries in terms of their response to the pandemic, and finally assess the effect of vaccination on pandemic control., Methods: The study covers 30 European countries: EU 27 in addition to Norway, Switzerland, and United Kingdom. Four epidemiological variables are analyzed at two distinct moments, at the end of 2020 and at the beginning of 2022: total number of cases per million, total number of deaths per million, total number of tests per thousand, and case fatality rate. In a second step, it uses a fuzzy approach, namely archetypal analysis, to identify epidemiological typologies, and positions countries by their response to the pandemic. Finally, it assesses how vaccination, stringency measures, booster doses and population age affect the case fatality rate, using a multiple regression model., Results: The outcomes unveil four epidemiological typologies for both periods. The clearest sign of change in the two periods concerns the case fatality rate that is found to be low in a single typology in 2020 but occurs in three typologies in 2022, although to different degrees. There is also statistical evidence of the positive impact of the primary vaccination on mortality reduction; however, the same does not hold for the booster dose and stringency measures., Conclusions: The study shows that primary vaccination is the most effective measure to reduce mortality by COVID-19 suggesting that vaccination provides hope for an end to the pandemic. However, a worldwide access to vaccination is needed to make this happen., (© 2022. The Author(s).)

Background: The COVID-19 pandemic has initiated several initiatives to better understand its behavior, and some projects are monitoring its evolution across countries, which naturally leads to comparisons made by those using the data. However, most "at a glance" comparisons may be misleading because the curve that should explain the evolution of COVID-19 is different across countries, as a result of the underlying geopolitical or socio-economic characteristics. Therefore, this paper contributes to the scientific endeavour by creating a new evaluation framework to help stakeholders adequately monitor and assess the evolution of COVID-19 in countries, considering the occurrence of spikes, "secondary waves" and structural breaks in the time series., Methods: Generalized Additive Models were used to model cumulative and daily curves for confirmed cases and deaths. The Root Relative Squared Error and the Percentage Deviance Explained measured how well the models fit the data. A local min-max function was used to identify all local maxima in the fitted values. The pure Markov-Switching and the family of Markov-Switching GARCH models were used to identify structural breaks in the COVID-19 time series. Finally, a quadrants system to identify countries that are more/less efficient in the short/long term in controlling the spread of the virus and the number of deaths was developed. Such methods were applied in the time series of 189 countries, collected from the Centre for Systems Science and Engineering at Johns Hopkins University., Results: Our methodology proves more effective in explaining the evolution of COVID-19 than growth functions worldwide, in addition to standardizing the entire estimation process in a single type of function. Besides, it highlights several inflection points and regime-switching moments, as a consequence of people's diminished commitment to fighting the pandemic. Although Europe is the most developed continent in the world, it is home to most countries with an upward trend and considered inefficient, for confirmed cases and deaths., Conclusions: The new outcomes presented in this research will allow key stakeholders to check whether or not public policies and interventions in the fight against COVID-19 are having an effect, easily identifying examples of best practices and promote such policies more widely around the world., (© 2021. The Author(s).)

Background: Primary Health Care (PHC) plays a crucial role in managing the COVID-19 pandemic, with only 8% of cases requiring hospitalization. However, PHC COVID-19 data often goes unnoticed on European government dashboards and in media discussions. This project aims to examine official information on PHC patient care during the COVID-19 pandemic in Europe, with specific objectives: (1) Describe PHC's clinical pathways for acute COVID-19 cases, including long-term care facilities, (2) Describe PHC COVID-19 pandemic indicators, (3) Develop COVID-19 PHC activity indicators, (4) Explain PHC's role in vaccination strategies, and (5) Create a PHC contingency plan for future pandemics. Methods: A mixed-method study will employ two online questionnaires to gather retrospective PHC data on COVID-19 management and PHC involvement in vaccination strategies. Validation will occur through focus group discussions with medical and public health (PH) experts. A two-wave Delphi survey will establish a European PHC indicators dashboard for future pandemics. Additionally, a coordinated health system action plan involving PHC, secondary care, and PH will be devised to address future pandemic scenarios. Analysis: Quantitative data will be analysed using STATA v16.0 for descriptive and multivariate analyses. Qualitative data will be collected through peer-reviewed questionnaires and content analysis of focus group discussions. A Delphi survey and multiple focus groups will be employed to achieve consensus on PHC indicators and a common European health system response plan for future pandemics. The Eurodata research group involving researchers from 28 European countries support the development. Discussion: While PHC manages most COVID-19 acute cases, data remains limited in many European countries. This study collects data from numerous countries, offering a comprehensive perspective on PHC's role during the pandemic in Europe. It pioneers the development of a PHC dashboard and health system plan for pandemics in Europe. These results may prove invaluable in future pandemics. However, data may have biases due to key informants' involvement and may not fully represent all European GP practices. PHC has a significant role in the management of the COVID-19 pandemic, as most of the cases are mild or moderate and only 8% needed hospitalization. However, PHC COVID-19 activity data is invisible on governments' daily dashboards in Europe, often overlooked in media and public debates. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a vasculitis of unknown origin of small and medium caliber blood vessels, especially involving coronary arteries and is the leading cause of acquired heart disease in childhood in developed countries. Although rarely, it can recur: most recurrences occur within 2 years of the initial episode. No data are available on incidence of recurrent KD in Europe and multiple recurrences are rarely seen. We reviewed the medical literature on Kawasaki disease recurrence and reported a new case of Kawasaki disease recurrence in a child with SARS-CoV-2 infection. We believe that in our case SARS Cov2 acted as a trigger capable to determine, in a genetically susceptible individual, a second recurrence of the disease. In the Covid-19 era we affirm the importance for Kawasaki disease to be tested for SARS Cov2 infection. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the Coronavirus disease 2019(COVID-19) vaccine policies disparities and effectiveness in Germany, Denmark and Bulgaria, with a view to providing lessons for global vaccination and response to possible outbreak risks. Methods: This study analyzed big data through public information on the official websites of the Ministries of Health of the European Union, Germany, Denmark and Bulgaria and the official websites of the World Health Organization. We systematically summarized the COVID-19 vaccine policies of the three countries, and selected the following six indicators for cross-cutting vaccination comparisons: COVID-19 vaccine doses administered per 100 people, COVID-19 vaccination rate, the share of people with fully vaccinated, the share of people only partly vaccinated, cumulative confirmed COVID-19 cases per million, cumulative confirmed COVID-19 deaths per million. Meanwhile, we selected the following four indicators for measuring the effectiveness of COVID-19 vaccine policy implementation: daily cases per million, daily deaths per million, the effective reproduction rate (Rt), the moving-average case fatality rate (CFR). Results: Although these three EU countries had the same start time for vaccination, and the COVID-19 vaccine supply was coordinated by the EU, there are still differences in vaccination priorities, vaccination types, and vaccine appointment methods. Compared to Germany and Denmark, Bulgaria had the least efficient vaccination efforts and the worst vaccination coverage, with a vaccination rate of just over 30% as of June 2023, and the maximum daily deaths per million since vaccination began in the country was more than three times that of the other two countries. From the perspective of implementation effect, vaccination has a certain effect on reducing infection rate and death rate, but the spread of new mutant strains obviously aggravates the severity of the epidemic and reduces the effectiveness of the vaccine. Among them, the spread of the Omicron mutant strain had the most serious impact on the three countries, showing an obvious epidemic peak. Conclusions: Expanding vaccination coverage has played a positive role in reducing COVID-19 infection and mortality rates and stabilizing Rt. Priority vaccination strategies targeting older people and at-risk groups have been shown to be effective in reducing COVID-19 case severity and mortality in the population. However, the emergence and spread of new variant strains, and the relaxation of epidemic prevention policies, still led to multiple outbreaks peaking. In addition, vaccine hesitancy, mistrust in government and ill-prepared health systems are hampering vaccination efforts. Among the notable ones are divergent types of responses to vaccine safety issue could fuel mistrust and hesitancy around vaccination. At this stage, it is also necessary to continue to include COVID-19 vaccination in priority vaccination plans and promote booster vaccination to prevent severe illness and death. Improving the fairness of vaccine distribution and reducing the degree of vaccine hesitancy are the focus of future vaccination work. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 control policies might negatively impact older adults' participation in volunteer work, instrumental support provision, and the likelihood of receiving instrumental support. Studies that quantify changes in these activities and the related factors are limited. The current study aimed to examine the level of volunteering, instrumental support provision and receipt before and during the first phase of the COVID-19 pandemic in Europe and to determine whether older adults' volunteering, instrumental support provision and receipt were associated with individual exposure to COVID-19 and the stringency of country's COVID-19 control policy during the first phase of the COVID-19 pandemic. Methods: A cross-sectional survey using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) Corona Survey 1 was designed to focus on community-dwelling Europeans aged ≥50 years. History of participation in volunteering work and instrumental support provision or receipt was assessed from the previous SHARE Wave data. The country's COVID-19 control policy stringency index (S-Index) was from the Oxford COVID-19 Government Response Tracker database. A total of 45,669 respondents from 26 European countries were included in the volunteering analysis. Seventeen European countries were included in the analyses of instrumental support provision (N = 36,518) and receipt (N = 36,526). The multilevel logistic regression model was fitted separately to analyse each activity. Results: The level of volunteering and instrumental support provision was lower during the pandemic, but instrumental support receipt was higher. The country S-Index was positively associated with support provision (OR:1.13;95%CI:1.02–1.26) and negatively associated with support receipt (OR:0.69;95%CI:0.54–0.88). Exposure to COVID-19 was positively associated with support receipt (OR:1.64;95%CI:1.38–1.95). COVID-19 exposure on close ones positively associated with volunteering (OR:1.47;95%CI:1.32–1.65), support provision (OR:1.28;95%CI:1.19–1.39), and support receipt (OR:1.25;95%CI:1.15–1.35). Conclusions: The COVID-19 pandemic impacted older Europeans' volunteering, instrumental support provision, and instrumental support receipt from outside their household. When someone close to them was exposed to COVID-19, older Europeans were likely to receive instrumental support and to volunteer and provide instrumental support. A stricter country's COVID-19 control policy might motivate older adults to provide instrumental support, but it prevents them from receiving instrumental support from outside their households. [ABSTRACT FROM AUTHOR]

Background: Emerging research suggests that physical activity among children and adolescents decreased during the COVID-19 pandemic. However, a differentiated overview of European youth is lacking. In particular, no systematic analysis has been conducted to date on the impact of heterogeneous pandemic restrictions and school closures within European countries, and with regard to potentially vulnerable groups. Methods: We searched seven databases and included studies for children and adolescents (≤ 19 years) of the WHO European Region that compared physical activity during the COVID-19 pandemic with a pre-pandemic baseline using validated measurement instruments. We used the Oxford Stringency Index and School Closure Index as indicators of restriction stringency. Screening for eligibility, data extraction, assessment of the study risk of bias (using the 'Risk of Bias in Non-randomized Studies - of Exposure' [ROBINS-E]) and certainty grading of evidence (using the GRADE approach), were all done in duplicate. Unpublished data was requested from study authors. Data were pooled in random effects models. An a priori protocol was published, reporting is carried out in accordance with the 'Preferred Reporting Items for Systematic Review and Meta-Analyses' (PRISMA) statement. Results: Of 14,897 non-duplicate records, 26 publications (n = 15,038 pre-pandemic, n = 13,041 during pandemic) met full inclusion criteria. Comparison before and during the COVID-19 pandemic revealed a significant reduction in total physical activity (standardized mean difference [SMD], -0.57 [95%CI, -0.95; -0.20]) and moderate-to-vigorous physical activity (SMD, -0.43 [95% CI, -0.75; -0.10]), corresponding to a decrease of 12 min per day (a 20% reduction of the WHO recommendation). A decrease in sporting activity was also recorded. Subgroup analyses suggested that middle childhood (aged 8–12) and adolescents were particularly affected by the decline. School closures were associated with a reduction in physical activity. The certainty of evidence for all outcomes was low. Conclusions: A sharp decline in all forms of physical activity was recorded among European children and adolescents during the COVID-19 pandemic. This decline was higher during periods of school closure and mainly affected younger schoolchildren and adolescents. Immediate action by policy-makers and practitioners, as well as evidence-based public health strategies, are imperative in reversing this trend. Trial registration: PROSPERO: CRD42023395871 [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 transmission dynamics have been greatly modulated by human contact behaviour. To curb the spread of the virus, global efforts focused on implementing both Non-Pharmaceutical Interventions (NPIs) and pharmaceutical interventions such as vaccination. This study was conducted to explore the influence of COVID-19 vaccination status and risk perceptions related to SARS-CoV-2 on the number of social contacts of individuals in 16 European countries. Methods: We used data from longitudinal surveys conducted in the 16 European countries to measure social contact behaviour in the course of the pandemic. The data consisted of representative panels of participants in terms of gender, age and region of residence in each country. The surveys were conducted in several rounds between December 2020 and September 2021 and comprised of 29,292 participants providing a total of 111,103 completed surveys. We employed a multilevel generalized linear mixed effects model to explore the influence of risk perceptions and COVID-19 vaccination status on the number of social contacts of individuals. Results: The results indicated that perceived severity played a significant role in social contact behaviour during the pandemic after controlling for other variables (p-value < 0.001). More specifically, participants who had low or neutral levels of perceived severity reported 1.25 (95% Confidence intervals (CI) 1.13 - 1.37) and 1.10 (95% CI 1.00 - 1.21) times more contacts compared to those who perceived COVID-19 to be a serious illness, respectively. Additionally, vaccination status was also a significant predictor of contacts (p-value < 0.001), with vaccinated individuals reporting 1.31 (95% CI 1.23 - 1.39) times higher number of contacts than the non-vaccinated. Furthermore, individual-level factors played a more substantial role in influencing contact behaviour than country-level factors. Conclusion: Our multi-country study yields significant insights on the importance of risk perceptions and vaccination in behavioral changes during a pandemic emergency. The apparent increase in social contact behaviour following vaccination would require urgent intervention in the event of emergence of an immune escaping variant. [ABSTRACT FROM AUTHOR]

Background: Considering the heterogenous evidence, a systematic review of the change in anxiety in European children and adolescents associated with the COVID-19 pandemic is lacking. We therefore assessed the change compared with pre-pandemic baselines stratified by gender and age as well as evaluated the impact of country-specific restriction policies. Methods: A registration on the 'International Prospective Register of Systematic Reviews' (PROSPERO) occurred and an a priori protocol was published. We searched six databases (PubMed, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, WHO COVID-19) using a peer-reviewed search string with citation tracking and grey literature screening. Primary outcomes were: (1) general anxiety symptoms; and (2) clinically relevant anxiety rates. We used the Oxford COVID-19 Stringency Index as an indicator of pandemic-related restrictions. Screening of title/abstract and full text as well as assessing risk of bias (using the 'Risk of Bias in Non-randomized Studies of Exposure' [ROBINS-E]) and certainty of evidence (using the 'Grading of Recommendations Assessment, Development and Evaluation' [GRADE]) was done in duplicate. We pooled data using a random effects model. Reporting is in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement. Results: Of 7,422 non-duplicate records, 18 studies with data from 752,532 pre-pandemic and 763,582 pandemic participants met full inclusion criteria. For general anxiety symptoms the total change effect estimate yielded a standardised mean difference (SMD) of 0.34 (95% confidence interval [CI], 0.17–0.51) and for clinically relevant anxiety rates we observed an odds ratio of 1.08 (95%-CI, 0.98–1.19). Increase in general anxiety symptoms was highest in the 11–15 years age group. Effect estimates were higher when pandemic-related restrictions were more stringent (Oxford Stringency Index > 60: SMD, 0.52 [95%-CI, 0.30–0.73]) and when school closures (School Closure Index ≥ 2: SMD, 0.44 [95%-CI, 0.23–0.65]) occurred. Conclusion: General anxiety symptoms among children and adolescents in Europe increased in a pre/during comparison of the COVID-19 pandemic; particularly for males aged 11–15 years. In periods of stringent pandemic-related restrictions and/or school closures a considerable increase in general anxiety symptoms could be documented. PROSPERO registration: CRD42022303714. [ABSTRACT FROM AUTHOR]

Background: Pandemics such as the COVID-19 pandemic and other severe health care disruptions endanger individuals to miss essential care. Machine learning models that predict which patients are at greatest risk of missing care visits can help health administrators prioritize retentions efforts towards patients with the most need. Such approaches may be especially useful for efficiently targeting interventions for health systems overburdened during states of emergency. Methods: We use data on missed health care visits from over 55,500 respondents of the Survey of Health, Ageing and Retirement in Europe (SHARE) COVID-19 surveys (June – August 2020 and June – August 2021) with longitudinal data from waves 1–8 (April 2004 – March 2020). We compare the performance of four machine learning algorithms (stepwise selection, lasso, random forest, and neural networks) to predict missed health care visits during the first COVID-19 survey based on common patient characteristics available to most health care providers. We test the prediction accuracy, sensitivity, and specificity of the selected models for the first COVID-19 survey by employing 5-fold cross-validation, and test the out-of-sample performance of the models by applying them to the data from the second COVID-19 survey. Results: Within our sample, 15.5% of the respondents reported any missed essential health care visit due to the COVID-19 pandemic. All four machine learning methods perform similarly in their predictive power. All models have an area under the curve (AUC) of around 0.61, outperforming random prediction. This performance is sustained for data from the second COVID-19 wave one year later, with an AUC of 0.59 for men and 0.61 for women. When classifying all men (women) with a predicted risk of 0.135 (0.170) or higher as being at risk of missing care, the neural network model correctly identifies 59% (58%) of the individuals with missed care visits, and 57% (58%) of the individuals without missed care visits. As the sensitivity and specificity of the models are strongly related to the risk threshold used to classify individuals, the models can be calibrated depending on users' resource constraints and targeting approach. Conclusions: Pandemics such as COVID-19 require rapid and efficient responses to reduce disruptions in health care. Based on characteristics available to health administrators or insurance providers, simple machine learning algorithms can be used to efficiently target efforts to reduce missed essential care. [ABSTRACT FROM AUTHOR]

Background: The aim of this cross-sectional study was to evaluate the course of self-reported mental distress and quality of life (QoL) of physicians, working in the outpatient care (POC). Outcomes were compared with a control group of physicians working in the inpatient care (PIC), throughout the Corona Virus Disease (COVID)-19 pandemic. The impact of risk and protective factors in terms of emotional and supportive human relations on mental distress and perceived QoL of POC were of primary interest. Methods: Within the largest prospective, multi-center survey on mental health of health care workers (HCW), conducted during the first (T1) and second (T2) wave of the COVID-19 pandemic in Europe, we investigated the course of current burden (CB), depression (Patient Health Questionnaire-2), anxiety (Generalized Anxiety Disorder-2) and QoL, cross-sectionally, in n = 848 POC (T1: n = 536, T2: n = 312). The primary outcomes were compared with an age- and gender-matchted control group of n = 458 PIC (T1: n = 262, T2: n = 196). COVID-19-, work-related, social risk and protective factors were examined. Results: At T1, POC showed no significant differences with respect to CB, depression, anxiety, and QoL, after Bonferroni correction. Whereas at T2, POC exhibited higher scores of CB (Cohen´s d/ Cd =.934, p <.001), depression (Cd = 1.648, p < 001), anxiety (Cd = 1.745, p <.001), work-family conflict (Cd = 4.170, p <.001) and lower QoL (Cd =.891, p =.002) compared with PIC. Nearly all assessed parameters of burden increased from T1 to T2 within the cohort of POC (e.g. depression: CD = 1.580, p <.001). Risk factors for mental distress of POC throughout the pandemic were: increased work-family conflict (CB: ß =.254, p <.001, 95% CI:.23,.28; PHQ-2: ß =.139, p =.011, 95% CI:.09,.19; GAD-2: ß =.207, p <.001, 95% CI:.16,.26), worrying about the patients´ security (CB: ß =.144, p =.007, 95% CI:.07,.22; PHQ-2: ß =.150, p =.006, 95% CI:.00,.30), fear of triage situations (GAD-2: ß =.132, p =.010, 95% CI: -.04,.31) and burden through restricted social contact in spare time (CB: ß =.146, p =.003, 95% CI:.07,.22; PHQ-2: ß =.187, p <.001, 95% CI:.03,.34; GAD-2: ß =.156, p =.003, 95% CI: -.01,.32). Protective factors for mental distress and QoL were the perceived protection by local authorities (CB: ß = -.302, p <.001, 95% CI: -.39, -.22; PHQ-2: ß = -.190, p <. 001, 95% CI: -.36, -.02; GAD-2: ß = -.211, p <.001, 95% CI: -.40, -.03; QoL: ß =.273, p <.001, 95% CI:.18,.36), trust in colleagues (PHQ-2: ß = -.181, p <.001, 95% CI: -.34, -.02; GAD-2: ß = -.199, p <.001, 95% CI: -.37, -.02; QoL: ß =.124, p =.017, 95% CI:.04,.21) and social support (PHQ-2: ß = -.180, p <.001, 95% CI: -.22, -.14; GAD-2: ß = -.127, p =.014, 95% CI: -.17, -.08; QoL: ß =.211, p <.001, 95% CI:.19,.23). Conclusions: During the pandemic, the protective role of emotional and supportive human relations on the mental distress and quality of life of POC should be taken into account more thoroughly, both in practice and future research. [ABSTRACT FROM AUTHOR]

Background: A growing number of studies point to a high mental health burden among children and adolescents during the COVID-19 pandemic, particularly concerning anxiety. However, the study quality and effect direction are heterogeneous in the existing primary studies with a lacking overview for the European continent. Therefore, this systematic review aims to critically synthesise the evidence regarding the impact of the COVID-19 pandemic on anxiety among children and adolescents in Europe compared to a pre-pandemic baseline. Methods: A systematic literature search will be performed in six databases (MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, and WHO COVID-19 database) with a peer reviewed search strategy according to the evidence-based checklist Peer Review of Electronic Search Strategies (PRESS). Inclusion criteria are children and adolescents ≤ 19 years living in Europe and data report during the COVID-19 pandemic with an appropriate pre-pandemic baseline. Primary outcomes are general anxiety symptoms and clinically relevant anxiety rates. Risk of bias will be assessed using the 'Risk of Bias in Non-randomised Studies of Exposure' (ROBINS-E). Data extraction will systematically include information on study design, population characteristics, COVID-19 determinants, pre-pandemic baseline, diagnostic instruments and outcome. The certainty of evidence for each outcome will be evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach adapted to the use of non-randomised studies. All process steps will be performed independently by two reviewers; any discrepancies will be discussed and, if necessary, resolved by a third author. Also, subgroup analysis, sensitivity analysis, publication bias analysis, and meta-regression analysis, if applicable, will be performed. The systematic review was registered in the Prospective Register of Systematic Reviews (PROSPERO) and the protocol was prepared in accordance to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. Discussion: This systematic review will address the lack of a critical and comprehensive summary of findings on the COVID-19 pandemic impact on anxiety among children and adolescents in Europe. In addition, it aims to identify pandemic-policy differences, such as the effect of school-closures, and identify particularly vulnerable risk groups. Systematic review registration: CRD42022303714 (PROSPERO). [ABSTRACT FROM AUTHOR]

Background: Research points to a high depression burden among youth during the COVID-19 pandemic; however, a lack of systematic evidence exists. We determine the change in depression symptoms among children and adolescents during COVID-19 compared to pre-pandemic baselines. By using country differences in pandemic-related restrictions and school closures in Europe as quasi-experimental design, we evaluate policy impacts on depression. Methods: In this systematic review and meta-analysis, following the PRISMA statement, we searched six databases (MEDLINE, EMBASE, PsycINFO, Cochrane Central, Web of Science, WHO COVID-19) using a peer-reviewed search string up until March 18, 2022 with citation tracking and grey literature searches. No limitations regarding language and effect measures existed. We included studies that compared (1) general depression symptoms or (2) clinically relevant depression rates in children and adolescents (≤ 19 years) before and during the COVID-19 pandemic in Europe. The validated Oxford Stringency Index was used as indicator for pandemic-related restrictions. Screening for eligibility, extracting data from published reports and from unpublished data requested directly from study authors, assessing the study risk of bias and grading certainty of evidence using the GRADE approach, were all done in duplicate. Data were pooled in a random-effects model. PROSPERO: CRD42022303714. Results: Of 7,422 nonduplicate records, 22 studies with data from 868,634 participants pre-pandemic and 807,480 during pandemic, met full inclusion criteria. For the comparison of depression symptoms before and during the COVID-19 pandemic, moderate certainty of evidence was observed for general depression symptoms (standardized mean difference, 0.21 [95%CI, 0.12–0.30]; I2 = 94%) and low certainty of evidence for clinically relevant depression rates (odds ratio, 1.36 [95%CI, 1.05–1.76]; I2 = 95%) for total population. Increase in general depression symptoms was higher for male adolescents, whereas increase in clinically relevant depression rates was higher for females. Effect estimates were significantly higher when pandemic-related restrictions were more stringent or school closure occurred. Conclusion: An increase in depression symptoms occurred in a pre-pandemic vs. during-pandemic comparison within the COVID-19 pandemic, whereby pandemic-related restrictions (such as school closures) resulted in a considerable effect increase. Ensuring adequate supply of mental health recovery services and long-term monitoring is of high public health relevance. [ABSTRACT FROM AUTHOR]

Background: Assessing the impact of government responses to Covid-19 is crucial to contain the pandemic and improve preparedness for future crises. We investigate here the impact of non-pharmaceutical interventions (NPIs) and infection threats on the daily evolution of cross-border movements of people during the Covid-19 pandemic. We use a unique database on Facebook users' mobility, and rely on regression and machine learning models to identify the role of infection threats and containment policies. Permutation techniques allow us to compare the impact and predictive power of these two categories of variables. Results: In contrast with studies on within-border mobility, our models point to a stronger importance of containment policies in explaining changes in cross-border traffic as compared with international travel bans and fears of being infected. The latter are proxied by the numbers of Covid-19 cases and deaths at destination. Although the ranking among coercive policies varies across modelling techniques, containment measures in the destination country (such as cancelling of events, restrictions on internal movements and public gatherings), and school closures in the origin country (influencing parental leaves) have the strongest impacts on cross-border movements. Conclusion: While descriptive in nature, our findings have policy-relevant implications. Cross-border movements of people predominantly consist of labor commuting flows and business travels. These economic and essential flows are marginally influenced by the fear of infection and international travel bans. They are mostly governed by the stringency of internal containment policies and the ability to travel. [ABSTRACT FROM AUTHOR]

Background: The closing of bars, restaurants and international borders during the COVID-19 pandemic led to significant changes in alcohol availability. This study provides a first systematic overview of the monthly development of alcohol sales in Europe during the pandemic in order to determine the effect of closed borders on the sales and consumption of alcohol.Methods: The study covers 72 months from January 2015 to December 2020 in 14 countries from northern, central and western Europe with excise revenue data for beer, spirits, wine separately and summed, converted into litres of pure alcohol per capita 15+ as a proxy for alcohol sales. March-December 2020 is seen as the pandemic period. The analyses consist of (1) descriptive trends of sales before and during the pandemic, (2) assessment of the pandemic impact on sales by time-series analyses and (3) case studies of countries and a region with substantial cross-border inflow or outflow of alcohol.Results: The result shows an overall reduction in alcohol sales with 3.6% during the pandemic. Nevertheless, the results differ based on the level of cross-border purchasing flows pre-pandemic, as countries with high cross-border inflow saw an increase in domestic sales as the pandemic hit. Norway, for example, saw a 23% increase in domestic sales during the pandemic period March-December 2020 compared to the same period in 2019.Conclusion: The closing of intra-European borders had a significant redistributing effect on alcohol sales. While noting sales increases, cross-border inflow countries generally saw a decrease in total amount of alcohol consumed per capita as not all cross-border purchases were replaced by domestic sales. This has important policy implications as large volumes of cross-border inflow of alcohol can negatively affect excise revenue as well as public health outcomes. The methodology can be used to further explore the reliance of different purchasing streams in a domestic alcohol market. [ABSTRACT FROM AUTHOR]

Background: Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). Objectives: We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. Methods: We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. Results: Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8–40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1–0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. Conclusions: During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally. [ABSTRACT FROM AUTHOR]

Background: Spain has been hit hard by COVID-19 since March 2020, especially in its metropolitan areas. We share experiences from Barcelona in measuring socioeconomic inequalities in the incidence of COVID-19 in the different waves, and in implementing coordinated and equity-oriented public health policy responses. Methods: We collected daily data on confirmed COVID-19 cases, geocoded the address of residence to assign each case to one of the 73 neighborhoods and 1068 census tracts, and calculated the cumulative incidence of COVID-19 by neighborhood and five income groups (quintiles of census tracts) by sex across four waves of the pandemic. We adjusted hierarchical Bayesian spatial models to obtain the relative risk (RR) of cumulative incidences in each quintile compared with the richest areas. A variety of public health policies implemented to tackle the pandemic and especially these inequalities in COVID-19 incidence and vaccination are selected and described. Results: Area-level income inequalities in the incidence of COVID-19 were present at different degree in all four waves. In the second wave (10/1/2020 to 12/6/2020), RR for the poorest income quintile census tracts compared with the richest was 1.43 (95% credible interval-CI-: 1.22–1.67) for men and 1.58 (95% CI: 1.35–1.83) for women. Later, inequalities in vaccination coverage also arose. Equity-oriented policy responses included: "health hotels" or home delivery of basic products for individuals with COVID-19 and without adequate conditions for isolation; new emergency facilities for homeless people, including those with active drug use; mass screening in high incidence areas; contingency plans for nursing homes and schools; adapting community health programs for their early reactivation; digital self-appointment support points and community vaccination days. Conclusion: COVID-19 hit Barcelona neighborhoods unequally, with variations between waves. The rapid availability of geolocalized data and by socioeconomic level helped public authorities to implement targeted policies and collaborative interventions for the most vulnerable populations. Further studies would be needed to evaluate their impact. [ABSTRACT FROM AUTHOR]

The article focuses on report by World Health Organization revealing death occurred in people older than 60 years due to COVID-19 in the European Region. Topics discussed include protection of each nation's older adults and to promote intergenerational equity and solidarity, and priori age cut-offs to decide who should get access to healthcare, as such ideas discriminate against older people.

Background: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance.Methods: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance.Results: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001).Conclusions: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates. [ABSTRACT FROM AUTHOR]