The need for holistic, longitudinal and comparable, real-time assessment of the emotional, behavioral and societal impact of the COVID-19 pandemic across nations

As of the end of 2020, the COVID-19 pandemic has led to over 82 million verified infections and almost 1.8 million COVID-19-related deaths worldwide,1 resulting to an unprecedented public health response around the globe. The COVID-19 pandemic, together with the applied multi-level restrictive measures, has generated a unique combination of an unpredictable and stressful biomedical and socioeconomic environment (i.e., syndemic),2 introducing real-life threat, involuntary and drastic every-day life-style changes with uncertain financial and future prospects, alongside with minimized coping and stress management possibilities.3 This combination of so many different and vital stressors may lead to acute as well as long-term, direct, indirect and even transgenerational unfavourable effects on physical and mental health and functioning, which might even represent the most precarious and still unpredictable public-health-related part of the pandemic.4 Thereby, specific population groups could be at particular risk of poor health outcomes in relation to applied public health measures.4, 5 However, not every individual will experience the same level of negative impact on health and well-being during the pandemic, as several additional national, socioeconomic, environmental, behavioural, emotional and cognitive factors can moderate individual resilience and coping.6 Pandemic-related research should, thus, assess as many multidimensional risk and protective factors as possible in a longitudinal, large-scale and multi-national manner, enabling a profound and comprehensive understanding of the complex health and societal impact of the pandemic worldwide.7 Nevertheless, to date, most research findings are cross-sectional, report on small and non- representative samples from individual countries, or on specific population groups (e.g., health care workers, students, clinical populations) and usually assess only a very restricted set of outcomes and time-points. Thereby, only few studies assess coping strategies, medical history or detailed socioeconomic, demographic and environmental data. In addition, most studies leave behind linguistic differences, being available in one or at best two different languages. Such investigations of small outcome subsets within a narrow framework preclude a broader and clear understanding of the multifaceted pandemic impact on the general population and specific subgroups. Acknowledging these gaps in the existing literature, large- scale, collaborative research prospectively collecting and monitoring a broad range of real- time, multi-dimensional health-related, societal and behavioural outcome data from countries across the globe is currently explicitly needed. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH- FIT) envisions to fill this gap. Based on an easy-to-access webpage (www.coh-fit.com), COH- FIT is the currently largest-scale known international collaborative study of over 200 researchers around the globe, prospectively collecting the biggest set of multi-dimensional and multi-disciplinary data from 150 high, middle, and low-income countries in over 30 languages and in three different age groups (adults, adolescents, children) of the general population, focusing also on relevant at-risk subgroups. Albeit being a cross-sectional anonymous survey on an individual level, it is a longitudinal study on a population level, as data are collected continuously since April 2020 and until the WHO declares the end of the pandemic. In addition to snowball recruitment, this project also collects information from nationally representative samples. Furthermore, COH-FIT is the first study of this scale investigating pandemic effects on health and functioning measures between family members, while it also specifically assesses a large list of behavioral and coping factors (e.g., screen time, social media usage, physical activity, social interaction, religious practices, etc.) on outcomes of interest. COH-FIT also monitors changes in public health restrictive measures to enhance data harmonization across nations and time, and to better investigate their impact on physical and mental health, while it also collects information on changes in healthcare systems functioning. The COH-FIT project was worldwide first initiated in Greece after the ethics committee approval of the School of Medicine of the Aristotle University of Thessaloniki and is officially supported by the Hellenic Psychiatric Association, European Psychiatric Association, World Association of Social Psychiatry, ECNP Network on the Prevention of Mental Disorders and Mental Health Promotion, among many other national and international scientific associations. To date, COH-FIT has already collected >115,000 participations worldwide (>8,000 in Greece), but more participants are still needed, both during the second and third wave of the pandemic, as in the future, after the pandemic has ended. Currently, the COH-FIT survey actively collects the largest sample on multifactorial data on the impact of the COVD-19 pandemic on health and functioning not only in Greece, but around the globe. The elaborated design of COH-FIT and similar studies may allow a better identification of key parameters and population groups at increased risk during the pandemic, as well as potential targets for acute and long-term prevention or intervention strategies in the current as in possible future pandemics. A profound understanding of the health and societal impact of the pandemic could facilitate an optimized governmental, social and individual health preparedness during infection times8 and the bridging of individuals', societal and systemic needs and actions through multi-level guideline development with the aim to improve mental health outcomes globally

Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?

Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level

Trading volume and volatility : intraday evidence from the Athens stock exchange

With the present paper we document some standard statistical properties and 'stylized' facts of volume and volatility of nine common shares traded in the Athens Stock Exchange (ASE) * * *. Using econometrical tools we investigate the relationship between volume and volatility attempting to find support for the Mixture of Distribution Hypothesis (MDH). Although the Granger-causality results can support a trading volume equation the well documented property of volatility clustering cannot be supported by the data. Furthermore, the trading volume seems to convey no information for the stock exchange participants. So we could cast doubt in the hypothesis proposed by Lamoureux and Lastrapes (1990).peer-reviewe

Estimating a cost-effectiveness threshold for healthcare decision-making in the Greek NHS

Background: The introduction of new health technologies improves quality of life and longevity, but also imposes additional strains in the scarce resources of the health system. Consequently, decisions on the adoption of new technologies are typically based, among other criteria, on the difference between costs and outcomes among competing alternatives. This paper aims to estimate a cost-effectiveness threshold that can be used as an input in the decision-making process for the funding (or reimbursement) of health technologies in Greece. Methods: For a 30-year period, we calculate the Quality-Adjusted Life Expectancy (QALE) of the Greek population and regress it against per capita public health expenditure, using an instrumental variable approach and controlling for a set of covariates. The estimated coefficients of expenditure on QALE are used to inform a cost-effectiveness threshold, estimatead as the cost per QALY gained through a permanent increase in per capita spending. Results: Based on the estimated coefficient of health expenditure, we estimate a base case cost-effectiveness threshold of €27,117 per QALY gained for the Greek healthcare system, from a third-party payer perspective. Conclusions: In the Greek healthcare system, which is currently in the stage of establishing a comprehensive health technology assessment process, decision rules which are not based on heuristics or “rules of thumb”, are essential

Regional differences between North and South Greece at the turn of the century

Despite the confusion surrounding the measurement of public sector outputs with respect to their demand and their distribution, the growing abundance of statistical data on public expenditures has been given incentives to the investigators of public economics to undertake research on the determinants of such expenditures. Attention has been focused upon public expenditures in an attempt to redress the imbalance emphasized on the role of taxation only. Some one hundred years ago Adolph Wagner, the German economist has suggested that as the development of a Nation proceeds government expenditure would increase. The so called "law of expanding state activity" was empirically tested by a number of investigators. Wagner's law is tested in all these studies by observing the statistical significance of the income elasticity of public expenditures. Timm was the first to interpret Wagner's law from Wagner's original writings. Since Timm's important contribution there is a Despite the confusion surrounding the measurement of public sector outputs with respect to their demand and their distribution, the growing abundance of statistical data on public expenditures has been given incentives to the investigators of public economics to undertake research on the determinants of such expenditures. Attention has been focused upon public expenditures in an attempt to redress the imbalance emphasized on the role of taxation only. Some one hundred years ago Adolph Wagner, the German economist has suggested that as the development of a Nation proceeds government expenditure would increase. The so called "law of expanding state activity" was empirically tested by a number of investigators. Wagner's law is tested in all these studies by observing the statistical significance of the income elasticity of public expenditures. Timm was the first to interpret Wagner's law from Wagner's original writings. Since Timm's important contribution there is a significant number of researchers that attempted to verify Wagner's law. In these studies it seems that the investigators have some problems in identifying the correct definitions of the dependent and independent variables that enter Wagner's relation. As we will see the problem of the correct specification of Wagner's relation is also unsolved in the present study. The present article presents an attempt to verify Wagner's law for Greece. In order to have a significant result about its validity several specifications are estimated and tested. These specifications refer to the traditional as well as to some structural ones that associate the law with some special characteristics of the Greek economy. Therefore, in order to answer the question of what the Greek households get back for their money paid on taxes, we describe and give the traditional as well as the structural specifications of Wagner's relationship that we have estimated in the present study. Especially we emphasize the role of this "Law" in the North and South regional differences of Greece, at the turn of the century. Also, we describe the statistical data we have used and comment on the econometric problems that are associated with the estimation of the relationships. Finally, we present the results of the estimations and in the concluding section we summarized our results from the point of view of their precision and the implications that Wagner's law, has when accepted, for other macroeconomic variables of the Greek economy

Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation

Early life stressors display a high universal prevalence and constitute a major public health problem. Prolonged psychoneurobiological alterations as sequelae of early life stress (ELS) could represent a developmental risk factor and mediate risk for disease, leading to higher physical and mental morbidity rates in later life. ELS could exert a programming effect on sensitive neuronal brain networks related to the stress response during critical periods of development and thus lead to enduring hyper- or hypo-activation of the stress system and altered glucocorticoid signaling. In addition, alterations in emotional and autonomic reactivity, circadian rhythm disruption, functional and structural changes in the brain, as well as immune and metabolic dysregulation have been lately identified as important risk factors for a chronically impaired homeostatic balance after ELS. Furthermore, human genetic background and epigenetic modifications through stress-related gene expression could interact with these alterations and explain inter-individual variation in vulnerability or resilience to stress. This narrative review presents relevant evidence from mainly human research on the ten most acknowledged neurobiological allostatic pathways exerting enduring adverse effects of ELS even decades later (hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system and inflammation, oxidative stress, cardiovascular system, gut microbiome, sleep and circadian system, genetics, epigenetics, structural, and functional brain correlates). Although most findings back a causal relation between ELS and psychobiological maladjustment in later life, the precise developmental trajectories and their temporal coincidence has not been elucidated as yet. Future studies should prospectively investigate putative mediators and their temporal sequence, while considering the potentially delayed time-frame for their phenotypical expression. Better screening strategies for ELS are needed for a better individual prevention and treatment

CIN2+ detection of the HPV DNA Array genotyping assay in comparison with the Cobas 4800 HPV test and cytology

BACKGROUND: HPV DNA Array is an E1-targeting PCR genotyping test, with capability of distinguishing 18 high-risk (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) and 11 low-risk HPV types (6, 11, 40, 42, 44, 54, 67, 69, 70, 85, 97). HPV DNA Array uses multiplex PCR for E1-gene sequence amplification. The amplicons are detected and genotyped by reverse hybridization to immobilized DNA probes spotted as triplets in single 96 well-plate wells and read by AID ELISPOT reader. METHODS: Aim of the study was to evaluate the clinical performance of the assay against internationally accepted and FDA approved Cobas 4800 HPV test (Roche Diagnostics). Study population comprised of 500 cervical samples. RESULTS: HPV DNA Array demonstrated a very high sensitivity of 100% for CIN2+ and 100% for CIN3+ detection, same as Cobas 4800. HPV DNA Array showed greater sensitivity for CIN2+ detection than cytology (100% vs. 13.6%). The agreement to Cobas 4800 for HPV detection, irrespective of type, was 81.4% with κ = 0.613. The agreement for HPV 16 was 92.8% (κ = 0.929), and for HPV 18 54.2% (κ = 0.681). CONCLUSION: HPV DNA Array demonstrated good clinical performance for detection of high-grade lesions, and may be considered for usage in a screening setting