Effects of Drought on Mortality in Macro Urban Areas of Brazil Between 2000 and 2019.

A significant fraction of Brazil's population has been exposed to drought in recent years, a situation that is expected to worsen in frequency and intensity due to climate change. This constitutes a current key environmental health concern, especially in densely urban areas such as several big cities and suburbs. For the first time, a comprehensive assessment of the short-term drought effects on weekly non-external, circulatory, and respiratory mortality was conducted in 13 major Brazilian macro-urban areas across 2000-2019. We applied quasi-Poisson regression models adjusted by temperature to explore the association between drought (defined by the Standardized Precipitation-Evapotranspiration Index) and the different mortality causes by location, sex, and age groups. We next conducted multivariate meta-analytical models separated by cause and population groups to pool individual estimates. Impact measures were expressed as the attributable fractions among the exposed population, from the relative risks (RRs). Overall, a positive association between drought exposure and mortality was evidenced in the total population, with RRs varying from 1.003 [95% CI: 0.999-1.007] to 1.010 [0.996-1.025] for non-external mortality related to moderate and extreme drought conditions, from 1.002 [0.997-1.007] to 1.008 [0.991-1.026] for circulatory mortality, and from 1.004 [0.995-1.013] to 1.013 [0.983-1.044] for respiratory mortality. Females, children, and the elderly population were the most affected groups, for whom a robust positive association was found. The study also revealed high heterogeneity between locations. We suggest that policies and action plans should pay special attention to vulnerable populations to promote efficient measures to reduce vulnerability and risks associated with droughts

Functional Ag-Exchanged Zeolites as Biocide Agents

"This is the peer reviewed version of the following article: Cerrillo, José Luis, Antonio Eduardo Palomares, Fernando Rey, Susana Valencia, María Bernardita Pérez-Gago, Diana Villamón, and Lluís Palou. 2018. Functional Ag-Exchanged Zeolites as Biocide Agents. ChemistrySelect 3 (17). Wiley: 4676 82. doi:10.1002/slct.201800432, which has been published in final form at https://doi.org/10.1002/slct.201800432. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Materials based on silver are used for controlling different pathogenic microorganisms. However, the influence of the silver carrier in the biocidal activity of the material has been scarcely reported. The present research is focused on studying the influence of zeolite properties on the biocidal activity of silver-exchanged zeolites, acting as reservoirs of silver species. The biocidal action of Ag-Faujasite (Ag-FAU) and Ag-Linde Type A (Ag-LTA) zeolites, containing different silver contents, is studied against different types of bacteria and fungi. Importantly, zeolite structure is found to be a significant parameter for controlling the antibacterial activity of Ag-exchanged zeolites. The results show that Ag-FAU presents a higher activity than Ag-LTA, because the topology of FAU combined with its highest Si/Al ratio favors the formation and release of silver species with important biocidal activity. Some insights on the bactericidal mechanism of Ag-zeolites are envisaged by means of high resolution transmission electron microscopy, showing the multi-targeted biocidal action of Ag species released from zeolites. Besides, it is shown that Ag-zeolites are more active against bacteria than fungi. Antifungal activity is highly dependent on the fungi species and the structure of the zeolite is not as determinant as it is for the antibacterial activity.The authors thank the Spanish Ministry of Economy and Competitiveness through MAT-2015-71842-P and SEV-2016-0683 for the financial support and J.L. Cerrillo wish to thank Spanish Ministry of Economy and Competitiveness for the Severo Ochoa PhD fellowship (SVP-2014-068600).Cerrillo, JL.; Palomares Gimeno, AE.; Rey Garcia, F.; Valencia Valencia, S.; Pérez-Gago, MB.; Villamón-Pérez, D.; Palou-Valls, L. (2018). Functional Ag-Exchanged Zeolites as Biocide Agents. ChemistrySelect. 3(17):4676-4682. https://doi.org/10.1002/slct.201800432S46764682317Dai, D., Prussin, A. J., Marr, L. C., Vikesland, P. J., Edwards, M. A., & Pruden, A. (2017). Factors Shaping the Human Exposome in the Built Environment: Opportunities for Engineering Control. Environmental Science & Technology, 51(14), 7759-7774. doi:10.1021/acs.est.7b01097Klevens, R. 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Antibacterial Activity and Mechanism of Action of the Silver Ion in Staphylococcus aureus and Escherichia coli. Applied and Environmental Microbiology, 74(7), 2171-2178. doi:10.1128/aem.02001-07Sánchez, M. J., Mauricio, J. E., Paredes, A. R., Gamero, P., & Cortés, D. (2017). Antimicrobial properties of ZSM-5 type zeolite functionalized with silver. Materials Letters, 191, 65-68. doi:10.1016/j.matlet.2017.01.039Lalueza, P., Monzón, M., Arruebo, M., & Santamaría, J. (2011). Bactericidal effects of different silver-containing materials. Materials Research Bulletin, 46(11), 2070-2076. doi:10.1016/j.materresbull.2011.06.041Haile, T., Nakhla, G., Zhu, J., Zhang, H., & Shugg, J. (2010). Mechanistic study of the bactericidal action of silver-loaded chabasite on Acidithiobacillus thiooxidans. Microporous and Mesoporous Materials, 127(1-2), 32-40. doi:10.1016/j.micromeso.2009.06.030Saint-Cricq, P., Kamimura, Y., Itabashi, K., Sugawara-Narutaki, A., Shimojima, A., & Okubo, T. (2012). Antibacterial Activity of Silver-Loaded «Green Zeolites». European Journal of Inorganic Chemistry, 2012(21), 3398-3402. doi:10.1002/ejic.201200476Matsumura, Y., Yoshikata, K., Kunisaki, S., & Tsuchido, T. (2003). Mode of Bactericidal Action of Silver Zeolite and Its Comparison with That of Silver Nitrate. Applied and Environmental Microbiology, 69(7), 4278-4281. doi:10.1128/aem.69.7.4278-4281.2003Inglezakis, V. J. (2005). The concept of «capacity» in zeolite ion-exchange systems. Journal of Colloid and Interface Science, 281(1), 68-79. doi:10.1016/j.jcis.2004.08.082Fonseca, A. M., & Neves, I. C. (2013). Study of silver species stabilized in different microporous zeolites. Microporous and Mesoporous Materials, 181, 83-87. doi:10.1016/j.micromeso.2013.07.018Amorim, R., Vilaça, N., Martinho, O., Reis, R. M., Sardo, M., Rocha, J., … Neves, I. C. (2012). Zeolite Structures Loading with an Anticancer Compound As Drug Delivery Systems. The Journal of Physical Chemistry C, 116(48), 25642-25650. doi:10.1021/jp3093868Neves, I. C., Cunha, C., Pereira, M. R., Pereira, M. F. R., & Fonseca, A. M. (2010). Optical Properties of Nanostructures Obtained by Encapsulation of Cation Chromophores in Y Zeolite. The Journal of Physical Chemistry C, 114(24), 10719-10724. doi:10.1021/jp101001aGóra-Marek, K., Tarach, K. A., Piwowarska, Z., Łaniecki, M., & Chmielarz, L. (2016). Ag-loaded zeolites Y and USY as catalysts for selective ammonia oxidation. Catalysis Science & Technology, 6(6), 1651-1660. doi:10.1039/c5cy01446hDemirci, S., Ustaoğlu, Z., Yılmazer, G. A., Sahin, F., & Baç, N. (2013). Antimicrobial Properties of Zeolite-X and Zeolite-A Ion-Exchanged with Silver, Copper, and Zinc Against a Broad Range of Microorganisms. Applied Biochemistry and Biotechnology, 172(3), 1652-1662. doi:10.1007/s12010-013-0647-7Tekin, R., & Bac, N. (2016). Antimicrobial behavior of ion-exchanged zeolite X containing fragrance. Microporous and Mesoporous Materials, 234, 55-60. doi:10.1016/j.micromeso.2016.07.006Ferreira, L., Fonseca, A. M., Botelho, G., Aguiar, C. A.-, & Neves, I. C. (2012). Antimicrobial activity of faujasite zeolites doped with silver. Microporous and Mesoporous Materials, 160, 126-132. doi:10.1016/j.micromeso.2012.05.006Lalueza, P., Monzón, M., Arruebo, M., & Santamaria, J. (2011). Antibacterial action of Ag-containing MFI zeolite at low Ag loadings. Chem. Commun., 47(2), 680-682. doi:10.1039/c0cc03905eKawahara, K., Tsuruda, K., Morishita, M., & Uchida, M. (2000). Antibacterial effect of silver-zeolite on oral bacteria under anaerobic conditions. Dental Materials, 16(6), 452-455. doi:10.1016/s0109-5641(00)00050-6Bedi, R. S., Cai, R., O’Neill, C., Beving, D. E., Foster, S., Guthrie, S., … Yan, Y. (2012). Hydrophilic and antimicrobial Ag-exchanged zeolite a coatings: A year-long durability study and preliminary evidence for their general microbiocidal efficacy to bacteria, fungus and yeast. Microporous and Mesoporous Materials, 151, 352-357. doi:10.1016/j.micromeso.2011.10.012Chiericatti, C., Basílico, J. C., Basílico, M. L. Z., & Zamaro, J. M. (2014). Antifungal activity of silver ions exchanged in mordenite. Microporous and Mesoporous Materials, 188, 118-125. doi:10.1016/j.micromeso.2013.12.033Cerrillo, J. L., Palomares, A. E., Rey, F., Valencia, S., Palou, L., & Pérez-Gago, M. B. (2017). Ag-zeolites as fungicidal material: Control of citrus green mold caused by Penicillium digitatum. Microporous and Mesoporous Materials, 254, 69-76. doi:10.1016/j.micromeso.2017.03.036Mayoral, A., Carey, T., Anderson, P. A., & Diaz, I. (2013). Atomic resolution analysis of porous solids: A detailed study of silver ion-exchanged zeolite A. Microporous and Mesoporous Materials, 166, 117-122. doi:10.1016/j.micromeso.2012.04.033Kaur, B., Srivastava, R., Satpati, B., Kondepudi, K. K., & Bishnoi, M. (2015). Biomineralization of hydroxyapatite in silver ion-exchanged nanocrystalline ZSM-5 zeolite using simulated body fluid. Colloids and Surfaces B: Biointerfaces, 135, 201-208. doi:10.1016/j.colsurfb.2015.07.068Kwakye-Awuah, B., Williams, C., Kenward, M. A., & Radecka, I. (2008). Antimicrobial action and efficiency of silver-loaded zeolite X. Journal of Applied Microbiology, 104(5), 1516-1524. doi:10.1111/j.1365-2672.2007.03673.xSun, T., & Seff, K. (1994). Silver Clusters and Chemistry in Zeolites. Chemical Reviews, 94(4), 857-870. doi:10.1021/cr00028a001Sayah, E., Brouri, D., & Massiani, P. (2013). A comparative in situ TEM and UV–visible spectroscopic study of the thermal evolution of Ag species dispersed on Al2O3 and NaX zeolite supports. Catalysis Today, 218-219, 10-17. doi:10.1016/j.cattod.2013.06.003Satsuma, A., Shibata, J., Shimizu, K., & Hattori, T. (2005). Ag Clusters as Active Species for HC-SCR Over Ag-Zeolites. 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Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

BACKGROUND:The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient's distribution in relation to the questionnaire used. METHODS:136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. RESULTS:GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. CONCLUSIONS:Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT01388218

imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non-small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image-based deep-learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep-learning image-based classifier accurately identifies cancer, even when a limited number of samples are available.publishedVersio

Facilitators and barriers to physical activity following pulmonary rehabilitation in COPD: a systematic review of qualitative studies

Pulmonary rehabilitation has short-term benefits on dyspnea, exercise capacity and quality of life in COPD, but evidence suggests these do not always translate to increased daily physical activity on a patient level. This is attributed to a limited understanding of the determinants of physical activity maintenance following pulmonary rehabilitation. This systematic review of qualitative research was conducted to understand COPD patients’ perceived facilitators and barriers to physical activity following pulmonary rehabilitation. Electronic databases of published data, non-published data, and trial registers were searched to identify qualitative studies (interviews, focus groups) reporting the facilitators and barriers to physical activity following pulmonary rehabilitation for people with COPD. Thematic synthesis of qualitative data was adopted involving line-by-line coding of the findings of the included studies, development of descriptive themes, and generation of analytical themes. Fourteen studies including 167 COPD patients met the inclusion criteria. Seven sub-themes were identified as influential to physical activity following pulmonary rehabilitation. These included: intentions, self-efficacy, feedback of capabilities and improvements, relationship with health care professionals, peer interaction, opportunities following pulmonary rehabilitation and routine. These encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation and were identified as sub-themes within the three analytical themes, which were beliefs, social support, and the environment. The findings highlight the challenge of promoting physical activity following pulmonary rehabilitation in COPD and provide complementary evidence to aid evaluations of interventions already attempted in this area, but also adds insight into future development of interventions targeting physical activity maintenance in COPD

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P&lt;0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF &gt;35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P&lt;0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.</p

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and males and females compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 male; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between males and females (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 males and 3 females; log-rank P35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF

Interdigital cell death in the embryonic limb is associated with depletion of Reelin in the extracellular matrix

Interdigital cell death is a physiological regression process responsible for sculpturing the digits in the embryonic vertebrate limb. Changes in the intensity of this degenerative process account for the different patterns of interdigital webbing among vertebrate species. Here, we show that Reelin is present in the extracellular matrix of the interdigital mesoderm of chick and mouse embryos during the developmental stages of digit formation. Reelin is a large extracellular glycoprotein which has important functions in the developing nervous system, including neuronal survival; however, the significance of Reelin in other systems has received very little attention. We show that reelin expression becomes intensely downregulated in both the chick and mouse interdigits preceding the establishment of the areas of interdigital cell death. Furthermore, fibroblast growth factors, which are cell survival signals for the interdigital mesoderm, intensely upregulated reelin expression, while BMPs, which are proapototic signals, downregulate its expression in the interdigit. Gene silencing experiments of reelin gene or its intracellular effector Dab-1 confirmed the implication of Reelin signaling as a survival factor for the limb undifferentiated mesoderm. We found that Reelin activates canonical survival pathways in the limb mesoderm involving protein kinase B and focal adhesion kinase. Our findings support that Reelin plays a role in interdigital cell death, and suggests that anoikis (apoptosis secondary to loss of cell adhesion) may be involved in this process

Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature

Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966–2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966–2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK)

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription