Analysis of the Associations of Measurements of Body Composition and Inflammatory Factors with Cardiovascular Disease and Its Comorbidities in a Community-Based Study.

The associations of cardiovascular disease (CVD) with comorbidities and biochemical and body composition measurements are repeatedly described but have not been studied simultaneously. In the present cross-sectional study, information on CVD and comorbidities [type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HDL)], body composition, levels of soluble markers, and other measures were collected from 1079 individuals. When we examined the association of each comorbidity and CVD, controlling for other comorbidities, we observed a clear pattern of the comorbidity-related specific associations with tested covariates. For example, T2DM was significantly associated with GDF-15 levels and the leptin/adiponectin (L/A) ratio independently of two other comorbidities; HTN, similarly, was independently associated with extracellular water (ECW) levels, L/A ratio, and age; and HDL was independently related to age only. CVD showed very strong independent associations with each of the comorbidities, being associated most strongly with HTN (OR = 10.89, 6.46-18.38) but also with HDL (2.49, 1.43-4.33) and T2DM (1.93, 1.12-3.33). An additive Bayesian network analysis suggests that all three comorbidities, particularly HTN, GDF-15 levels, and ECW content, likely have a main role in the risk of CVD development. Other factors, L/A ratio, lymphocyte count, and the systemic inflammation response index, are likely indirectly related to CVD, acting through the comorbidities and ECW.

Pathogens Causing Pediatric Community Acquired Urinary Tract Infections and Their Increasing Antimicrobial Resistance: A Nationwide Study.

Urinary tract infections (UTIs) in childhood are common and are associated with considerable acute morbidity and long-term complications. The need for updated data to optimize empiric antibiotic therapy is crucial. We aimed to investigate the pathogens causing pediatric community acquired UTIs, their correlation with demographic characteristics, and trends in their antimicrobial resistance. This nationwide cross-sectional study included all 53,203 children (<18 years) diagnosed with UTI in community outpatient clinics in the following selected years: 2007, 2011, 2015, 2019 and 2021. Escherichia coli (E. coli) (82.1%) was the most common uropathogen, followed by Enterobacter, Klebsiella, Proteus, Pseudomonas, and Enterococcus species. The bacterial distribution displayed statistically significant (p < 0.0001) gender- and sector-specific patterns with a higher relative prevalence of non-E. coli UTI in Jewish and males. The rate of extended-spectrum beta-lactamase-positive E. coli increased substantially and significantly (p < 0.001) from only 6.1% in 2007 to 25.4% in 2021. Most non-E. coli uropathogens exhibited resistance to commonly used empiric antibiotics for UTIs in children. These findings are significant in guiding optimal empiric antibiotic treatment for pediatric community acquired UTIs. The resistance of uropathogens to antimicrobials is region- and time-dependent. Therefore, the periodic and local assessment of antibiotic resistance trends is essential to update guidelines and provide the most appropriate antibacterial therapy for children with UTIs.

Relationships between Circulating Biomarkers and Body Composition Parameters in Patients with Metabolic Syndrome: A Community-Based Study.

Metabolic syndrome (MetS) is a complex disease involving multiple physiological, biochemical, and metabolic abnormalities. The search for reliable biomarkers may help to better elucidate its pathogenesis and develop new preventive and therapeutic strategies. In the present population-based study, we looked for biomarkers of MetS among obesity- and inflammation-related circulating factors and body composition parameters in 1079 individuals (with age range between 18 and 80) belonging to an ethnically homogeneous population. Plasma levels of soluble markers were measured by using ELISA. Body composition parameters were assessed using bioimpedance analysis (BIA). Statistical analysis, including mixed-effects regression, with MetS as a dependent variable, revealed that the most significant independent variables were mainly adipose tissue-related phenotypes, including fat mass/weight (FM/WT) [OR (95% CI)], 2.77 (2.01-3.81); leptin/adiponectin ratio (L/A ratio), 1.50 (1.23-1.83); growth and differentiation factor 15 (GDF-15) levels, 1.32 (1.08-1.62); inflammatory markers, specifically monocyte to high-density lipoprotein cholesterol ratio (MHR), 2.53 (2.00-3.15), and a few others. Additive Bayesian network modeling suggests that age, sex, MHR, and FM/WT are directly associated with MetS and probably affect its manifestation. Additionally, MetS may be causing the GDF-15 and L/A ratio. Our novel findings suggest the existence of complex, age-related, and possibly hierarchical relationships between MetS and factors associated with obesity.

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study.

OBJECTIVE: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. METHODS: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD (N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio (N = 37,116). RESULTS: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p < .0001). CONCLUSIONS: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a doseresponse relationship.

Increased Rate of Familial Mediterranean Fever in Children With ADHD: A Population-Based Case-Control Study.

OBJECTIVE: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. METHODS: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. RESULTS: Fifty-six (0.30%) children with ADHD (N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18-2.51); p = .003]. CONCLUSIONS: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation.

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association. METHODS: The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case-controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08-1.25], p < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22-1.38], p < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01-1.24], p = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], p < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], p = 0.047). CONCLUSIONS: G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD.

Physician-Patient Communication Course: When the Inauguration of a New Israeli Medical School Coincided with COVID-19 Pandemic.

Purpose: The curriculum of the Adelson School of Medicine at Ariel University, the newly established sixth medical school in Israel, includes a simulation center-based extended course on physician-patient communication, aiming to help students master the core competency of interpersonal and communication skills. For more than a year following the emergence of the COVID-19 pandemic, the school suspended most face-to-face (F2F) encounters, transforming most teaching activities to remote platforms. The paper outlines the ways we adapted teaching of this course to these circumstances, the reactions of students and mentors to the changes and results of 1st year students' survey. Methods: During the lockdown in the first year 48 of 70 first-year students participated in a voluntary anonymous online evaluation of the course assessing motivation to become a physician; perceptions, feelings and attitudes towards the communication course, and advantages and disadvantages of online and F2F medical interviews. Results: 46.1% of the responding students reported that the pandemic strengthened their desire to become physicians. 56.3% claimed that they were able to a relatively large extent to empathize with COVID-19 patients who were exposed to the virus; 79.1% viewed their mentors as positive role models of communication skills. The students were able to receive and offer social support to their peers. They evaluated very highly the short instructional videos produced by the faculty. Conclusion: During the lockdown, the respondents generally indicated positive attitudes towards the communication course, the mentors and the inclusion of physician-patient communication as a topic in medical education. The students and mentors reported many disadvantages and few advantages of remote learning. Yet inevitably remote learning including online-based simulations is a step towards preparations for future practice within virtual medical care and telemedicine. The limitations of this study include the cross-sectional design, small sample size and self-reporting.

Pediatric antibiotic stewardship programs in Europe: a pilot survey among delegates of The European Academy of Pediatrics.

Background: Antimicrobial resistance (AMR) is one of the leading causes of morbidity and mortality worldwide. Efforts to promote the judicious use of antibiotics and contain AMR are a priority of several medical organizations, including the WHO. One effective way to achieve this goal is the deployment of antibiotic stewardship programs (ASPs). This study aimed to survey the current situation of pediatric ASPs in European countries and establish a baseline for future attempts to harmonize pediatric ASPs and antibiotic use in Europe. Methods: A web-based survey was conducted among national delegates of the European Academy of Paediatrics (EAP). The survey assessed the presence of pediatric ASPs in the representatives' countries in the inpatient and outpatient settings, the staff included in the programs, and their detailed activities regarding antibiotic use. Results: Of the 41 EAP delegates surveyed, 27 (66%) responded. Inpatient pediatric ASPs were reported in 74% (20/27) countries, and outpatient programs in 48% (13/27), with considerable variability in their composition and activities. Guidelines for managing pediatric infectious diseases were available in nearly all countries (96%), with those for neonatal infections (96%), pneumonia (93%), urinary tract (89%), peri-operative (82%), and soft tissue (70%) infections being the most common. Pediatric ASPs were reported at the national (63%), institutional (41%), and regional/local (<15%) levels. Pediatricians with infectious disease training (62%) and microbiologists (58%) were the most common members of the program personnel, followed by physician leaders (46%), infectious disease/infection control physicians (39%), pharmacists (31%), and medical director representatives (15%). Activities of the pediatric ASPs included educational programs (85%), monitoring and reporting of antibiotic use (70%) and resistance (67%), periodic audits with feedback (44%), prior approval (44%), and post-prescription review of selected antibiotic agents (33%). Conclusion: Although pediatric ASPs exist in most European countries, their composition and activities vary considerably across countries. Initiatives to harmonize comprehensive pediatric ASPs across Europe are needed.

The Association of Weight Reduction and Other Variables after Bariatric Surgery with the Likelihood of SARS-CoV-2 Infection.

BACKGROUND AND AIMS: Although obesity has been confirmed as a risk factor for SARS-CoV-2 infection and its severity, the role of post-bariatric surgery (BS) variables and the infection is unclear. We, therefore, aimed to study comprehensively the relationship between the extent of weight reduction after surgery and other demographic, clinical, and laboratory variables with the rates of SARS-CoV-2 infection. METHODS: A population-based cross-sectional study was performed, utilizing advanced tracking methodologies on the computerized database of a nation-wide health maintenance organization (HMO). The study population included all HMO members aged ≥18 years that had been tested at least once for SARS-CoV-2 during the study period and underwent BS at least one year before their testing. RESULTS: Of the total 3038 individuals who underwent BS, 2697 (88.78%) were positive for SARS-CoV-2 infection and 341 (11.22%) were negative. Multivariate regression analysis demonstrated that the body mass index and the amount of weight reduction after the BS were not related to the likelihood of SARS-CoV-2 infection. Post-operative low socioeconomic status (SES) and vitamin D3 deficiency were associated with significant and independent increased rates of SARS-CoV-2 infection (odds ratio [OR] 1.56, 95% confidence interval [CI], 1.19-2.03, p < 0.001; and OR 1.55, 95% CI, 1.18-2.02, p < 0.001; respectively). Post-operative physical activity > 3 times/week was associated with a significant and independent reduced rate of SARS-CoV-2 infection (OR 0.51, 95% CI, 0.35-0.73, p < 0.001). CONCLUSION: Post-BS vitamin D3 deficiency, SES, and physical activity, but not the amount of weight reduction, were significantly associated with the rates of SARS-CoV-2 infection. Healthcare workers should be aware of these associations after BS and intervene accordingly.

Process of drug registration in Israel: the correlation between the number of discussions within the Ministry of Health and postapproval variations by EMA and/or FDA.

OBJECTIVES: US FDA and EMA allow facilitated regulatory pathways to expedite access to new treatments. Limited supportive data may result in major postapproval variations. In Israel, partly relying on Food and Drug Administration (FDA) and European Medicines Agency (EMA), clinical data are reviewed independently by the Advisory Committee of Drug Registration (ACDR). In this study, the correlation between the number of discussions at the ACDR and major postapproval variations is examined. DESIGN: This is an observational retrospective comparative cohort study. SETTING: Applications with FDA and/or EMA approval at time of assessment in Israel were included. The timeframe was chosen to allow a minimum of 3 years of postmarketing approval experience for potential major label variations. Data regarding the number of discussions at ACDR were extracted from protocols. Data on postapproval major variations were extracted from the FDA and EMA websites. RESULTS: Between 2014 and 2016, 226 (176 drugs) applications, met the study criteria. 198 (87.6%) and 28 (12.4%) were approved following single and multiple discussions, respectively. A major postapproval variation was recorded in 129 (65.2%) compared with 23 (82.1%) applications approved following single and multiple discussions, respectively (p=0.002). Increased risk for major variation was found for medicines approved following multiple discussions (HR=1.98, 95% CI: 1.26 to 3.09) with a median time of 1.2 years, applications approved based on phase II trials (HR=2.58, 95% CI: 1.72 to 3.87), surrogate endpoints (HR=1.99, 95% CI: 1.44 to 2.74) and oncologic indications (HR=2.48, 95% CI: 1.78 to 3.45). CONCLUSIONS: Multiple ACDR discussions associated with limited supportive data are predictive for major postapproval variations. Moreover, our findings demonstrate that approval by the FDA and/or EMA does not pave the way to automatic approval in Israel. In a substantial per cent of the cases, submission of the same clinical data resulted in different safety and efficacy considerations, requiring additional supporting data in some cases or even rejection of the application in others.

The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study.

Background: The susceptibility to SARS-CoV-2 infection is complex and not yet fully elucidated, being related to many variables; these include human microbiome and immune status, which are both affected for a long period by antibiotic use. We therefore aimed to examine the association of previous antibiotic consumption and SARS-CoV-2 infection in a large-scale population-based study with control of known confounders. Methods: A matched case-control study was performed utilizing the electronic medical records of a large Health Maintenance Organization. Cases were subjects with confirmed SARS-CoV-2 infection (n = 31,260), matched individually (1:4 ratio) to controls without a positive SARS-CoV-2 test (n = 125,039). The possible association between previous antibiotic use and SARS-CoV-2 infection was determined by comparing antibiotic consumption in the previous 6 and 12 months between the cases and controls. For each antibiotic consumed we calculated the odds ratio (OR) for documented SARS-CoV-2 infection, 95% confidence interval (CI), and p-value using univariate and multivariate analyses. Results: The association between previous antibiotic consumption and SARS-CoV-2 infection was complex and bi-directional. In the multivariate analysis, phenoxymethylpenicillin was associated with increased rate of SARS-CoV-2 infection (OR 1.110, 95% CI: 1.036-1.191) while decreased rates were associated with previous consumption of trimethoprim-sulfonamides (OR 0.783, 95% CI: 0.632-0.971) and azithromycin (OR 0.882, 95% CI: 0.829-0.938). Fluroquinolones were associated with decreased rates (OR 0.923, 95% CI: 0.861-0.989) only in the univariate analysis. Previous consumption of other antibiotics had no significant association with SARS-CoV-2 infection. Conclusions: Previous consumption of certain antibiotic agents has an independent significant association with increased or decreased rates of SARS-CoV-2 infection. Plausible mechanisms, that should be further elucidated, are mainly antibiotic effects on the human microbiome and immune modulation.

Bacterial vs viral etiology of fever: A prospective study of a host score for supporting etiologic accuracy of emergency department physicians.

BACKGROUND: A host-protein score (BV score) that combines the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10) and C-reactive protein (CRP) was developed for distinguishing bacterial from viral infection. This study assessed the potential of the BV score to impact decision making and antibiotic stewardship at the emergency department (ED), by comparing BV score's performance to physician's etiological suspicion at patient presentation. METHODS: Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. 465 patients were recruited, 298 met eligibility criteria and 287 were enrolled. ED physician's etiological suspicion was recorded in a questionnaire. BV score was measured retrospectively with results interpreted as viral, bacterial or equivocal and compared to reference standard etiology, which was adjudicated by three independent experts based on all available data. Experts were blinded to BV scores. RESULTS: Median age was 1.3 years (interquartile range 1.7), 39.7% females. 196 cases were reference standard viral and 18 cases were reference standard bacterial. BV score attained sensitivity of 88.9% (95% confidence interval: 74.4-100), specificity 92.1% (88.1-96.0), positive predictive value 53.3% (35.5-71.2) and negative predictive value 98.8% (97.1-100). Positive likelihood ratio was 11.18 (6.59-18.97) and negative likelihood ratio was 0.12 (0.03-0.45). The rate of BV equivocal scores was 9.4%. Comparing physician's suspicion to BV score and to the reference standard, and assuming full adoption, BV score could potentially correct the physician's diagnosis and reduce error ~2-fold, from 15.9% to 8.2%. CONCLUSIONS: BV score has potential to aid the diagnostic process. Future studies are warranted to assess the impact of real-time BV results on ED practice.

Threshold protective levels of serum IgG to Shigella lipopolysaccharide: re-analysis of Shigella vaccine trials data.

OBJECTIVES: Establishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis. METHODS: We performed new analyses of serologic and vaccine efficacy (VE) data from two randomized vaccine-controlled trials of the Shigella sonnei-Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate conducted in young adults and children aged 1-4 years in Israel. Adults received either S. sonnei-rEPA (n = 183) or control vaccines (n = 277). Children received the S. sonnei-rEPA conjugate (n = 1384) or S. flexneri 2a-rEPA conjugate (n = 1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti-S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti-S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and the reverse cumulative distribution of IgG levels. RESULTS: Among adults, four vaccinees and 23 controls developed S. sonnei shigellosis; the VE was 74% (95% CI, 28-100%). A threshold of ≥1:1600 IgG anti-S. sonnei LPS titre was associated with a reduced risk of S. sonnei shigellosis and a predicted VE of 73.6% (95% CI, 65-80%). The IgG anti-S. sonnei LPS correlated with serum bactericidal titres. In children, a population-based level of 4.5 ELISA Units (EU) corresponding to 1:1072 titre, predicted VE of 63%, versus 71% observed VE in children aged 3-4 years. The predicted VE in children aged 2-4 years was 49%, consistent with the 52% observed VE. CONCLUSION: Serum IgG anti-S. sonnei LPS threshold levels can predict the degree of VE and can be used for the evaluation of new vaccine candidates.

Attention-Deficit/Hyperactivity Disorder Is Associated With Increased Rates of Childhood Infectious Diseases: A Population-Based Case-Control Study.

OBJECTIVE: Infectious diseases (IDs) pose a heavy burden on children. An association between pediatric attention-deficit/hyperactivity disorder (ADHD) and specific IDs has been documented. Our objective was to test the possibility that ADHD is associated with increased likelihood for pediatric IDs at large. METHOD: A population-based case-control study was conducted using Electronic Medical Records (EMRs) of a national Health Maintenance Organization, Leumit Health Services (LHS). ICD-9/10 criteria were used for all diagnoses. The study population consisted of all children and adolescents (aged 5-18 years), members of LHS between January 1, 2006-June 30, 2021. Case patients met International Classification of Diseases (ICD-9/10) criteria for ADHD. Controls included randomly selected persons without ADHD (2:1 ratio), matched individually by demographic indices. The EMRs retrieved 3 exposure categories: pediatric ID, anti-infective medications use, and number of physician visits. The study was approved by the review board of Shamir Medical Center and the Research Committee of LHS. RESULTS: Cases patients comprised 18,756 participants, with a mean age of 8.3 ± 2.6 years and a male/female ratio of 63%:37%. Matched controls comprised 37,512 participants, with a mean age of 8.3 ± 2.6 years and a male/female ratio of 63%:37%. Demographic variables were similar between the groups. The rates of all IDs were significantly higher in participants with ADHD than in controls and were not restricted to a single body system, including acute respiratory infection (OR = 1.4, 95% CI = 1.3-1.4, p < .001), acute gastroenteritis (OR = 1.3,95% CI 1.3-1.4, p < .001), salmonellosis (OR = 2.8, 95% CI = 2.3-3.5, p < .001), and urinary tract infection (OR = 1.3, 95% CI = 1.2-1.4, p < .001). All anti-infective agents were prescribed significantly more often to children with ADHD. There were significantly higher rates of physician visits for participants with ADHD. CONCLUSION: Study findings suggest an association between ID and pediatric ADHD Health care providers should be aware of this potential association. CLINICAL TRIAL REGISTRATION INFORMATION: The Health and Economic Impact of Treated and Untreated ADHD; https://www.shamir.org/; 005-18-LEU.

A higher frequency of physical activity is associated with reduced rates of SARS-CoV-2 infection.

BACKGROUND: Physical activity (PA) is associated with health benefits. Previous studies have shown that regular PA decreases the incidence of viral respiratory tract infections, but data on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are unavailable. OBJECTIVES: The objective of this study is to examine the association between PA frequency and SARS-CoV-2 infection. METHODS: A population-based cross-sectional study was conducted on data from 1 February 2020 to 31 December 2020, using the registry of Leumit Health Services (LHS), a national health maintenance organisation in Israel. All LHS patients aged 18 to 80 years who underwent at least one RT-PCR test for SARS-CoV-2 during the study period were included. We examined the association between PA frequency (hours per week) and being tested positive for SARS-CoV-2. RESULTS: Of 113,075 subjects tested for SARS-CoV-2 by RT-PCR (mean age 41.6 years, 54.4% female), 17,465 (15%) were positive. In the SARS-CoV-2-negative group, significantly more subjects were engaged with PA than in the SARS-CoV-2-positive group [crude odds ratio (OR) for any PA 0.75 (95% confidence interval (CI) 0.72-0.77)]. After adjusting for possible confounders, PA frequency had a significant negative association with the likelihood of being SARS-CoV-2 positive (adjusted OR 0.67, 95% CI 0.64-0.68). Moreover, as the frequency of PA increased, the ORs of being SARS-CoV-2-positive decreased (occasional PA: OR 0.71, 95% CI 0.67-0.74; PA 1-3 times/week: OR 0.62, 95% CI 0.58-0.65 and PA > 3 times/week: OR 0.54, 95% CI 0.49 - 0.59). CONCLUSION: Our large population-based study in patients undergoing SARS-CoV-2 RT-PCR testing showed that a higher frequency of PA is associated with a lower rate of positive test results.

Early Detection and Control of the Next Epidemic Wave Using Health Communications: Development of an Artificial Intelligence-Based Tool and Its Validation on COVID-19 Data from the US.

Social media networks highly influence on a broad range of global social life, especially in the context of a pandemic. We developed a mathematical model with a computational tool, called EMIT (Epidemic and Media Impact Tool), to detect and control pandemic waves, using mainly topics of relevance on social media networks and pandemic spread. Using EMIT, we analyzed health-related communications on social media networks for early prediction, detection, and control of an outbreak. EMIT is an artificial intelligence-based tool supporting health communication and policy makers decisions. Thus, EMIT, based on historical data, social media trends and disease spread, offers an predictive estimation of the influence of public health interventions such as social media-based communication campaigns. We have validated the EMIT mathematical model on real world data combining COVID-19 pandemic data in the US and social media data from Twitter. EMIT demonstrated a high level of performance in predicting the next epidemiological wave (AUC = 0.909, F1 = 0.899).

Clozapine Suppresses the Gene Expression and the Production of Cytokines and Up-Regulates Cyclooxygenase 2 mRNA in Human Astroglial Cells.

Schizophrenia (SCZ) is a chronic neurodevelopmental psychotic disorder. The immune system and neuroinflammation seem to play a central role in the pathophysiology of SCZ. Clozapine is an effective atypical antipsychotic used for treatment-resistant SCZ. Life-threatening side effects, such as myocarditis, limit its use. We investigated the immunomodulatory effects of clozapine in an astroglial model of neuroinflammation. We thus assessed the effect of clozapine on the production of inflammatory mediators in human-derived astroglial (A172) cells, stimulated with a cytokine mix (TNFα, IL-1ß, IFNγ). RT-PCR and ELISA analyses demonstrated that clozapine suppressed gene expression and production of TNFα, IL-1ß and IL-8 and increased COX2 mRNA 24 h after stimulation. Clozapine inhibited Akt phosphorylation induced by the cytokine mix at 10 min and 40 min, as assessed by Western blot analysis with anti-pT308Akt antibody. Pretreatment with the Akt inhibitor MK-2206 increased COX2 gene expression in cytokine-stimulated cells, suggesting that Akt inhibition may be involved in COX2 gene expression upregulation. Clozapine may possess dual beneficial effects: inhibiting astroglial production of proinflammatory cytokines, thus attenuating neuroinflammation, and upregulating COX2 expression that may be relevant to improvement of neural functioning while accounting for some of its detrimental effects. Patients with TRS and neuroinflammatory markers may benefit particularly from clozapine treatment.