Tobacco policies and changes in the tendency of smoking cessation in cigarette users in Chile: a longitudinal cross-sectional study.

OBJECTIVE: To assess the impact of tobacco control regulations and policy implementation on smoking cessation tendencies in cigarette users born between 1982 and 1991 in Chile. DESIGN: Longitudinal cross-sectional study. SETTING: National level. PARTICIPANTS: Data from the National Survey of Drug Consumption (Service of Prevention and Rehabilitation for Drug and Alcohol Consumption). A pseudo-cohort of smokers born between 1982 and 1991 (N=17 905) was tracked from 2002 to 2016. PRIMARY AND SECONDARY OUTCOMES MEASURES: Primary outcome was the tendency to cease smoking conceptualised as the report of using cigarettes 1 month or more ago relative to using cigarettes in the last 30 days. The main exposure variable was the Tobacco Policy Index-tracking tobacco policy changes over time. Logistic regression, controlling for various factors, was applied. RESULTS: Models suggested a 14% increase in the smoking cessation tendency of individuals using cigarettes 1 month or more ago relative to those using cigarettes in the last 30 days (OR 1.14, CI 95% CI 1.10 to 1.19) for each point increment in the Tobacco Policy index. CONCLUSIONS: Our study contributes to documenting a positive impact of the implementation of interventions considered in the MPOWER strategy in the progression of smoking cessation tendencies in smokers born between 1982 and 1991 in Chile.

Reactivation of Trypanosoma cruzi infection in immunosuppressed patients: a systematic review and meta-analysis.

BACKGROUND: The risk of Trypanosoma cruzi reactivation is poorly understood. Previous studies evaluating the risk of reactivation report imprecise findings, and recommendations for monitoring and management from clinical guidelines rely on consensus opinion. OBJECTIVES: We conducted a systematic review and meta-analysis to estimate the cumulative T. cruzi reactivation incidence in immunosuppressed adults, summarise the available evidence on prognostic factors for reactivation, and examine its prognostic effect on mortality. DATA SOURCES: MEDLINE, Embase and LILACS, Clinical trials, and CENTRAL from inception to 4 July 2022. STUDY ELIGIBILITY CRITERIA: Studies reporting the incidence of T. cruzi reactivation. PARTICIPANTS: Immunosuppressed adults chronically infected by T. cruzi. METHODS: Two authors independently extracted data (including, but not limited to, incidence data, reactivation definition, follow-up, treatment, monitoring schedule, examined prognostic factors) and evaluated the risk of bias. We pooled cumulative incidence using a random-effects model. RESULTS: Twenty-two studies (806 participants) were included. The overall pooled incidence of T. cruzi reactivation was 27% (95% CI 19-36), with the highest pooled proportion in the subgroup of transplant recipients (36%, 95% CI 25-48). The highest risk period was in the first six months post-transplant (32%, 95% CI 17-58), decreasing drastically the number of new cases later. People living with HIV and patients with autoimmune diseases experienced significantly lower cumulative reactivation incidences (17%, 95% CI 8-29; and 18%, 95% CI 9-29; respectively). A single study explored the independent effect of benznidazole and found benefits for preventing reactivations. No studies evaluated the independent association between reactivation and mortality, while sensitivity analysis results using unadjusted estimates were inconclusive. Heterogeneity of diagnostic algorithms was substantial. CONCLUSIONS: Reactivation occurs in three out of ten T. cruzi-seropositive immunosuppressed adults. These findings can assist clinicians and panel guidelines in tailoring monitoring schedules. There is a great need for an accurate definition of reactivation and targeted monitoring.

Gut microbiota composition in travellers is associated with faecal lipocalin-2, a mediator of gut inflammation.

Introduction: We examined the gut microbiota of travellers returning from tropical areas with and without traveller's diarrhoea (TD) and its association with faecal lipocalin-2 (LCN2) levels. Methods: Participants were recruited at the Hospital Clinic of Barcelona, Spain, and a single stool sample was collected from each individual to perform the diagnostic of the etiological agent causing gastrointestinal symptoms as well as to measure levels of faecal LCN2 as a biomarker of gut inflammation. We also characterised the composition of the gut microbiota by sequencing the region V3-V4 from the 16S rRNA gene, and assessed its relation with the clinical presentation of TD and LCN2 levels using a combination of conventional statistical tests and unsupervised machine learning approaches. Results: Among 61 participants, 45 had TD, with 40% having identifiable etiological agents. Surprisingly, LCN2 levels were similar across groups, suggesting gut inflammation occurs without clinical TD symptoms. Differential abundance (DA) testing highlighted a microbial profile tied to high LCN2 levels, marked by increased Proteobacteria and Escherichia-Shigella, and decreased Firmicutes, notably Oscillospiraceae. UMAP analysis confirmed this profile's association, revealing distinct clusters based on LCN2 levels. The study underscores the discriminatory power of UMAP in capturing meaningful microbial patterns related to clinical variables. No relevant differences in the gut microbiota composition were found between travellers with or without TD. Discussion: The findings suggest a correlation between gut microbiome and LCN2 levels during travel, emphasising the need for further research to discern the nature of this relationship.

Different Diagnostic Criteria for Determining the Prevalence of Sarcopenia in Older Adults: A Systematic Review.

Background: Sarcopenia is defined as a loss of muscle mass, strength, and physical function associated with aging. It is due to a combination of genetic, environmental, and physiological factors. It is also associated with an increased risk of health problems. Since there are many different researchers in the field, with their own algorithms and cut-off points, there is no single criterion for diagnosis. This review aims to compare the prevalence of sarcopenia according to these different diagnostic criteria in older adult populations by age group and sex. Methods: Different databases were searched: Web of Science, Pubmed, Dialnet, Scopus, and Cochrane. The keywords used were "sarcopenia", "diagnosis", "prevalence", "assessment", "aged", "aging" and "older". Studies conducted in a population aged ≥65 assessing the prevalence of sarcopenia were selected. Results: Nineteen articles met the inclusion criteria, with a total of 33,515 subjects, 38.08% female and 61.42% male, at a mean age of 74.52. The diagnostic algorithms used were 52.63% AWGS2, 21.05% EWGSOP2, 10.53% AWGS1 and EWGS1, and 5.26% FNIH. Prevalence ranged from 1.7% to 37.47%, but was higher in males and increased with age. Conclusions: The prevalence of sarcopenia varies depending on the diagnostic algorithm used, but it increases with age and is higher in men. The EWGSOP2 and AWGS2 are the most used diagnostic criteria and measure the same variables but have different cut-off points. Of these two diagnostic algorithms, the one with the highest prevalence of sarcopenia and severe sarcopenia is the AWGS2. These differences may be due to the use of different tools and cut-off points. Therefore, a universal diagnostic criterion should be developed to allow early diagnosis of sarcopenia.

Considerations about the inhibition of monophenolase and diphenolase activities of tyrosinase. Characterization of the inhibitor concentration which generates 50 % of inhibition, type and inhibition constants. A review.

Tyrosinase is a copper oxidase enzyme which catalyzes the first two steps in the melanogenesis pathway, L-tyrosine to L-dopa conversion and, then, to o-dopaquinone and dopachrome. Hypopigmentation and, above all, hyperpigmentation issues can be originated depending on their activity. This enzyme also promotes the browning of fruits and vegetables. Therefore, control of their activity by regulators is research topic of great relevance. In this work, we consider the use of inhibitors of monophenolase and diphenolase activities of the enzyme in order to accomplish such control. An experimental design and data analysis which allow the accurate calculation of the degree of inhibition of monophenolase activity (iM) and diphenolase activity (iD) are proposed. The IC50 values (amount of inhibitor that causes 50 % inhibition at a fixed substrate concentration) can be calculated for the two activities and from the values of IC50M (monophenolase) and IC50D(diphenolase). Additionally, the strength and type of inhibition can be deduced from these values. The data analysis from these IC50D values allows to obtain the values of [Formula: see text] or [Formula: see text] , or and [Formula: see text] from the values of IC50M. In all cases, the values of the different must satisfy their relationship with IC50M and IC50D.

Prevalence of diagnosed and undiagnosed osteoarthrosis and associated factors in the adult general Spanish population.

OBJECTIVE: To determine the prevalence and related factors of diagnosed osteoarthrosis (DO) and undiagnosed osteoarthrosis (UO) in the general Spanish adult population. SETTING: Cross-sectional study with data from the Spanish National Health Survey 2017. PARTICIPANTS: N=23,089 adults. Three groups of people were defined: DO, UO, and no osteoarthrosis (NO). MAIN MEASUREMENTS: Sociodemographic information, lifestyle (tobacco, alcohol, physical activity, body mass index) and health factors (intensity of pain, pain drug consumption, mental health, self-perceived health status, pain involvement in daily living) were collected. Descriptive and bivariate analyses were performed, and a multinomial logistic regression model for the factors associated with each group. RESULTS: The prevalence of DO was 22.4% (95%CI=21.8;22.9) and 0.9% (95%CI=0.8;1) of UO. With respect to NO, risk factors for DO and UO included higher pain levels and pain drug consumption. Better self-perceived health status was inversely related with both. More pain involvement in daily living was associated with increased risk of DO, but reduced risk of UO. CONCLUSIONS: The prevalence of DO and UO was similar to that reported in Europe, but slightly higher than in low/middle-income countries. It was more prevalent in females, older people, people with worse perceived health status and worse mental health. Higher pain levels and pain drug consumption were risk factors for DO and UO. Better self-perceived health status was protective. Pain involvement in daily living was a risk factor for DO, but protective for UO. Different public health strategies should be considered in view of this.

Machine learning approach to identify malaria risk in travelers using real-world evidence.

Background: Pre-travel consultation and chemoprophylaxis measures for malaria are a key component in the prevention of imported malaria in travelers. In this study we report a predictive tool for assessing personalized malaria risk in travelers based on the analysis of electronic medical records from travel consultations. The tool aims to guide physicians in the recommendation of appropriate prophylaxis prior to their trip. We also provide best-practice recommendations for pre-processing noisy and highly sparse real world evidence data. Methods: We leveraged a large EMR dataset, containing demographic information about travelers and their destination. The data has been previously preprocessed using various strategies to handle missing and unbalanced data. We compared multiple machine learning approaches to assess the risk of malaria acquisition in travelers during their travels. Additionally, a feature importance analysis was performed using SHAP (SHapley Additive Explanations) values to identify patterns associated with malaria risk. Results: Our study revealed that our XGB models achieved high predictive capacity (AUC >0.80). The most significant features predicting malaria infection during travel included travel destinations with low malaria risk, vaccination history, number of countries visited, age, and trip duration. Remarkably, we were able to obtain a reduced model with only five features. When comparing this model with a population of travelers recommended for malaria chemoprophylaxis, we observed that it was deemed necessary in only 40% of these travelers. This suggests that 60% received chemoprophylaxis despite having a low personalized risk of malaria. Conclusion: We have developed an algorithmic tool that utilizes a concise survey to generate a personalized travel risk assessment, effectively minimizing the prescription of unnecessary malaria chemoprophylaxis. Through the identification of patterns linked to predictions, our model significantly enhances the efficacy of pre-travel consultations.

MALrisk: a machne-learning based tool to predict imported malaria in returned travellers with fever.

BACKGROUND: Early diagnosis is key to reducing the morbi-mortality associated with P. falciparum malaria among international travellers. However, access to microbiological tests can be challenging for some healthcare settings. Artificial Intelligence could improve the management of febrile travellers. METHODS: Data from a multicentric prospective study of febrile travellers was obtained to build a machine-learning model to predict malaria cases among travellers presenting with fever. Demographic characteristics, clinical and laboratory variables were leveraged as features. Eleven machine-learning classification models were evaluated by 50-fold cross-validation in a Training set. Then, the model with the best performance, defined by the Area Under the Curve (AUC), was chosen for parameter optimization and evaluation in the Test set. Finally, a reduced model was elaborated with those features that contributed most to the model. RESULTS: Out of eleven machine-learning models, XGBoost presented the best performance (mean AUC of 0.98 and a mean F1 score of 0.78). A reduced model (MALrisk) was developed using only six features: Africa as a travel destination, platelet count, rash, respiratory symptoms, hyperbilirubinemia and chemoprophylaxis intake. MALrisk predicted malaria cases with 100% (95%CI 96-100) sensitivity and 72% (95%CI 68-75) specificity. CONCLUSIONS: The MALrisk can aid in the timely identification of malaria in non-endemic settings, allowing the initiation of empiric antimalarials and reinforcing the need for urgent transfer in healthcare facilities with no access to malaria diagnostic tests. This resource could be easily scalable to a digital application and could reduce the morbidity associated with late diagnosis.

A case of possible transfusion-acquired malaria in Zaragoza, Spain.

We present the case of a 75-year-old patient diagnosed with malaria, a native of Zaragoza, Spain, despite having no travel history to malaria-endemic regions. Following an extensive investigation, transfusion emerged as the most probable mode of transmission.

Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes.

Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1ß mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.

Structural characterization of two nanobodies targeting the ligand-binding pocket of human Arc.

The activity-regulated cytoskeleton-associated protein (Arc) is a complex regulator of synaptic plasticity in glutamatergic neurons. Understanding its molecular function is key to elucidate the neurobiology of memory and learning, stress regulation, and multiple neurological and psychiatric diseases. The recent development of anti-Arc nanobodies has promoted the characterization of the molecular structure and function of Arc. This study aimed to validate two anti-Arc nanobodies, E5 and H11, as selective modulators of the human Arc N-lobe (Arc-NL), a domain that mediates several molecular functions of Arc through its peptide ligand binding site. The structural characteristics of recombinant Arc-NL-nanobody complexes were solved at atomic resolution using X-ray crystallography. Both anti-Arc nanobodies bind specifically to the multi-peptide binding site of Arc-NL. Isothermal titration calorimetry showed that the Arc-NL-nanobody interactions occur at nanomolar affinity, and that the nanobodies can displace a TARPγ2-derived peptide from the binding site. Thus, both anti-Arc-NL nanobodies could be used as competitive inhibitors of endogenous Arc ligands. Differences in the CDR3 loops between the two nanobodies indicate that the spectrum of short linear motifs recognized by the Arc-NL should be expanded. We provide a robust biochemical background to support the use of anti-Arc nanobodies in attempts to target Arc-dependent synaptic plasticity. Function-blocking anti-Arc nanobodies could eventually help unravel the complex neurobiology of synaptic plasticity and allow to develop diagnostic and treatment tools.

Uneven effects of twenty years of Chile's cannabis policy implementation in cannabis onset.

BACKGROUND: In Chile, Laws 19366 and 20000, implemented in 1995 and 2005 respectively, regulated and sanctioned cannabis' personal use, cultivation and trafficking. METHODS: We use thirteen biannual cross-sectional national surveys data from 1994 to 2018 to examine the effect of Laws 19366 and 20000-using the rate of individuals incarcerated per 100000 population due to drug-related crimes as proxy-on the age of onset of cannabis use over time. We estimate the effect of these policies using a mixed proportional hazards framework that models the transition to first cannabis use in 47,832 individuals aged 12-21. RESULTS: Overall, changes in these laws did not affect the transition to first cannabis use. However, increases in the rate of individuals incarcerated were associated with decreases on the age of onset of cannabis use in females and individuals living in affluent neighborhoods or in specific regions. CONCLUSION: We find no evidence of cannabis policy changes affecting the age of onset of cannabis use across all individuals aged 12-21. Policy effects associated with decreases in cannabis onset age in females and individuals from affluent neighborhoods or specific regions can be explained by using theoretical frames that recognize specific dynamics of cannabis supply and demand.

Patients Living with Arterial Hypertension in Mexico: First Insights of The Mexican Registry of Arterial Hypertension (RIHTA Study).

BACKGROUND: Arterial hypertension is a significant cause of morbidity and mortality in Mexico. However, there is limited data available to understand blood pressure management and cardiometabolic profiles. AIMS: To assess the prevalence of controlled and uncontrolled blood pressure, as well as the prevalence of cardiometabolic risk factors among patients from the Mexican Registry of Arterial Hypertension (RIHTA). METHODS: We conducted a cross-sectional analysis of participants living with arterial hypertension registered on RIHTA between December 2021 and April 2023. We used both the 2017 ACC/AHA and 2018 ESC/ESH thresholds to define controlled and uncontrolled arterial hypertension. We considered eleven cardiometabolic risk factors, which include overweight, obesity, central obesity, insulin resistance, diabetes, hypercholesterolemia, hypertriglyceridemia, low-HDL-C, high-LDL-C, low-eGFR, and high CVD risk. RESULTS: In a sample of 5,590 participants (female: 61%, n=3,393; median age: 64 [IQR: 56-72] years), the prevalence of uncontrolled hypertension varied significantly, depending on the definition (2017 ACC/AHA: 59.9%, 95% CI: 58.6-61.2 and 2018 ESC/ESH: 20.1%, 95% CI: 19.0-21.2). In the sample, 40.43% exhibited at least 5-6 risk factors, and 32.4% had 3-4 risk factors, chiefly abdominal obesity (83.4%, 95% CI: 82.4-84.4), high-LDL-C (59.6%, 95% CI: 58.3-60.9), high-CVD risk (57.9%, 95% CI: 56.6-59.2), high triglycerides (56.2%, 95% CI: 54.9-57.5), and low-HDL-C (42.2%, 95% CI: 40.9-43.5). CONCLUSION: There is a high prevalence of uncontrolled hypertension interlinked with a high burden of cardiometabolic comorbidities in Mexican adults living with arterial hypertension, underscoring the urgent need for targeted interventions and better healthcare policies to reduce the burden of the disease in our country.

Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study.

BACKGROUND: Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited. METHODS: Travellers returning with fever were prospectively recruited in three referral clinics from November 2017 to November 2019. Unbiased mNGS optimised for virus detection was performed on serum samples of participants with acute undifferentiated febrile illness (AUFI), and results were compared to those obtained by reference diagnostic methods (RDM). RESULTS: Among 507 returned febrile travellers, 433(85.4%) presented with AUFI. Dengue virus (n = 86) and Plasmodium spp. (n = 83) were the most common causes of fever. 103/433(23.8%) AUFI remained undiagnosed at the end of the follow-up.Metagenomic next-generation sequencing unveiled potentially pathogenic microorganisms in 196/433(38.7%) AUFI. mNGS identifications were more common in patients with a shorter duration of fever (42.3% in ≤5 days vs 28.7% in >5 days, P = 0.005). Potential causes of fever were revealed in 25/103(24.2%) undiagnosed AUFI and 5/23(21.7%) travellers with severe undiagnosed AUFI. Missed severe aetiologies included eight bacterial identifications and one co-infection of B19 parvovirus and Aspergillus spp.Additional identifications indicating possible co-infections occurred in 29/316(9.2%) travellers with AUFI, and in 11/128(8.6%) travellers with severe AUFI, who had received a diagnosis through RDM. The most common co-infections detected in severe AUFI were caused by Gram-negative bacteria. Serum mNGS was unable to detect >50% of infectious diagnoses achieved by RDM and also yielded 607 non-pathogenic identifications. DISCUSSION: mNGS of serum can be a valuable diagnostic tool for selected travellers with undiagnosed AUFI or severe disease in addition to reference diagnostic techniques, especially during the first days of symptoms. Nevertheless, mNGS results interpretation presents a great challenge. Further studies evaluating the performance of mNGS using different sample types and protocols tailored to non-viral agents are needed.

High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage.

Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases' prevention.

Changes in the Activity of the Erector Spinae and Gluteus Medius Muscles with the Presence of Simulated Lower Limb Dysmetria.

(1) Background: Leg length discrepancy (LLD), regardless of its origin, is a very common pathology that can contribute to low back pain. Various authors have pointed out its relationship with the lack of activation of both the gluteus medius (GM) and the ipsilateral erector spinae (ES). The purpose of this study was to identify the activation of the ES and GM with different simulated LLDs, correlating this activation with LBP. In turn, we evaluated whether ES and GM activity has an effect on jumping ability using a CMJ test. (2) Method: A sample of healthy subjects was selected to whom an artificial LLD was applied using 0.5, 1, and 1.5 cm insoles. These three heights were measured using EMG while the subjects walked and performed a counter movement jump (CMJ). The measurements of the insole heights were carried out in random order using a Latin square. Muscle activation patterns were recorded for 30 s at each of the insole heights while the patients walked at 5.7 km/h and they were compared with the maximum voluntary contraction (MVC), both on the ipsilateral and contralateral sides. These muscles were then measured under the same circumstances during the performance of the CMJ. (3) Results: We found statistically significant differences in the flight heights in both the CMJ and DJ. In the comparison, significant differences were found in the flight heights of the CMJ and the DJ using the 5 mm insoles, and in the case of the DJ, also without insoles, with respect to the MVC. We found statistically significant differences in the activation of the GM with the differences in insoles, but not in the activation of the Es in relation to the different insole heights. (4) Conclusions: Insoles of different heights caused activation differences in the medius on the side where the insoles were placed. We can relate this difference in activation to LBP. In relation to the ES, no significant differences were found in the activation of the ipsilateral side of the insole.

Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States.

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.

Tissue engineering in otorhinolaryngology: A knowledge-based analysis.

Objective: To analyze the impact, performance, degree of specialization, and collaboration patterns of the worldwide scientific production on tissue engineering in otorhinolaryngology at the level of countries and institutions. Methods: Two different techniques were used, performance and science mapping analyses, using as samples all the available documents regarding tissue engineering focused on otorhinolaryngology applications. The dataset was retrieved from the Core Collection of the Web of Science database from 1900 to 2020. Social structure was analyzed using science mapping analysis with VOSviewer software. Results: The United States was the main producer, followed by Germany, and Japan. Malaysia and Germany had the highest Relative Specialization Index, indicating their greater relative interest in this area compared to other countries. The social structure analysis showed that the United States and Germany had significant co-authorship relationships with other countries. The University of California System, Kyoto University, and Harvard University were the leading institutions producing literature in this field. These latter two institutions showed the largest number of collaborations, although most of them were with institutions within their own country. There was a lack of connections between different communities of research. Conclusion: The United States is the main country driving progress in this research area, housing the most notable institutions. However, significant collaborations between these research centers are currently lacking. Encouraging greater cooperation among these institutions and their researchers would promote the exchange of knowledge, ultimately facilitating and accelerating advancements in this field.