Mapping current status and emerging trends in NETosis: A bibliometric study.

BACKGROUND: NETosis is a critical innate immune mechanism of neutrophils that contributes to the accelerated progression of autoimmune diseases, thrombosis, cancer, and coronavirus disease 2019 (COVID-19). This study qualitatively and quantitatively analyzed the relevant literature by bibliometric methods in order to provide a more comprehensive and objective view of the knowledge dynamics in the field. METHODS: The literature on NETosis was downloaded from the Web of Science Core Collection, analyzed with VOSviewer, CiteSpace, and Microsoft for co-authorship, co-occurrence, and co-citation analysis. RESULTS: In the field of NETosis, the United States was the most influential countries. Harvard University was the most active institutions. Mariana J. Kaplan and Brinkmann V were, respectively, the most prolific and most co-cited authors. Frontiers in Immunology, Journal of Immunology, Plos One, Blood, Science, Journal of Cell Biology, and Nature Medicine were the most influential journals. The top 15 keywords are associated with immunological and NETosis formation mechanisms. The keywords with the strongest burst detection were mainly related to COVID-19 (coronavirus, ACE2, SARS coronavirus, cytokine storm, pneumonia, neutrophil to lymphocyte ratio), and cancer (circulating tumor cell). CONCLUSION: Research on NETosis is currently booming. The mechanism of NETosis and its role in innate immunity, autoimmune diseases, especially systemic lupus erythematosus and rheumatoid arthritis, and thrombosis are the focus of research in the field of NETosis. A future study will concentrate on the function of NETosis in COVID-19 and recurrent metastasis of cancer.

Corrigendum: Identification and analysis of SARS-CoV-2 alpha variants in the largest Taiwan COVID-19 outbreak in 2021.

[This corrects the article DOI: 10.3389/fmed.2022.869818.].

Suicidal ideation among young adults in Canada during the COVID-19 pandemic: evidence from a population-based cross-sectional study. / Idées suicidaires chez les jeunes adultes au Canada pendant la pandémie de COVID-19 : données tirées d'une enquête populationnelle transversale.

Using data from the 2020 and 2021 cycles of the Survey on COVID-19 and Mental Health,we examined suicidal ideation among adults in Canada aged 18 to 34 years. The prevalence of suicidal ideation among adults aged 18 to 34 years was 4.2% in fall 2020 and 8.0% in spring 2021. The subgroup of adults aged 18 to 24 years had the highest prevalence of suicidal ideation, 10.7%, in spring 2021. Prevalence varied by sociodemographic characteristics and tended to be higher among people living in materially deprived areas. Suicidal ideation was strongly associated with pandemic-related stressors respondents experienced.

In spring 2021, the prevalence of suicidal ideation among young adults aged 18 to 34 years was 8.0%. At 10.7%, the prevalence of suicidal ideation was highest in the subgroup of young adults aged 18 to 24 years, in spring 2021. The odds of suicidal ideation were higher among young adults who were White versus racialized, born in Canada versus immigrated to Canada, living with low or middle income, with high school education or less, or living in a materially deprived area. Pandemic-related experiences, stressful events and mental illness were strongly associated with suicidal ideation.

La prévalence des idées suicidaires chez les jeunes adultes de 18 à 34 ans était de 8,0 % au printemps 2021. La prévalence la plus élevée d'idées suicidaires, soit 10,7 %, correspond au sous-groupe des jeunes adultes de 18 à 24 ans au printemps 2021. Les probabilités d'idées suicidaires étaient plus élevées chez les jeunes adultes qui étaient d'origine blanche (par opposition aux membres d'un groupe « racisé ¼), ceux nés au Canada (par opposition à ceux ayant immigré au Canada), ceux vivant avec un revenu faible ou moyen, ceux ayant fait des études de niveau secondaire ou moins et ceux vivant dans un milieu défavorisé sur le plan matériel. Les expériences liées à la pandémie, les événements stressants et la maladie mentale étaient fortement associés aux idées suicidaires.

Generating and Weighting Semantically Consistent Sample Pairs for Ultrasound Contrastive Learning.

Well-annotated medical datasets enable deep neural networks (DNNs) to gain strong power in extracting lesion-related features. Building such large and well-designed medical datasets is costly due to the need for high-level expertise. Model pre-training based on ImageNet is a common practice to gain better generalization when the data amount is limited. However, it suffers from the domain gap between natural and medical images. In this work, we pre-train DNNs on ultrasound (US) domains instead of ImageNet to reduce the domain gap in medical US applications. To learn US image representations based on unlabeled US videos, we propose a novel meta-learning-based contrastive learning method, namely Meta Ultrasound Contrastive Learning (Meta-USCL). To tackle the key challenge of obtaining semantically consistent sample pairs for contrastive learning, we present a positive pair generation module along with an automatic sample weighting module based on meta-learning. Experimental results on multiple computer-aided diagnosis (CAD) problems, including pneumonia detection, breast cancer classification, and breast tumor segmentation, show that the proposed self-supervised method reaches state-of-the-art (SOTA). The codes are available at https://github.com/Schuture/Meta-USCL.

Short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer.

Background: The aim of this study was to explore the short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer (ER). Methods: Eighty-eight patients with ER cancer and 82 healthy controls who had completed a full course of inactivated or peptide-based SARS-CoV-2 vaccines were recruited. Adverse events (AEs) were recorded. Responses to receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD+ memory B cells (MBCs) were evaluated. Results: Approximately 26.14% (23/88) of patients with ER cancer reported AEs within 7 days, which was comparable to that reported by healthy controls (24.39%, 20/82). Both the overall seroprevalence of anti-RBD-IgG and NAbs was obviously lower in the cancer group (70.45% vs. 86.59%, P < 0.05; 69.32% vs. 82.93%, P < 0.05, respectively). Anti-RBD-IgG and NAbs titers exhibited similar results, and dropped gradually over time. Patients with ongoing treatment had an attenuated immune response, especially in patients receiving active chemotherapy. The frequency of overall RBD+ MBCs was similar between the two groups, but the percentage of active MBCs was remarkably reduced in patients with ER cancer. Unlike antibody titers, MBCs responses were relatively constant over time. Conclusion: Inactivated and peptide-based COVID-19 vaccines were well tolerated, but with lower immunogenicity for ER cancer patients. More intensive antibody monitoring and timely booster immunization is recommended for patients with ER cancer presenting disordered subpopulations of RBD+ MBCs.

Global Disease Burden and Attributable Risk Factor Analysis of Asthma in 204 Countries and Territories From 1990 to 2019.

PURPOSE: Asthma is a common chronic inflammatory respiratory tract disease with high morbidity and mortality. The global trends in asthma burden remain poorly understood, and asthma incidence has increased during the worldwide coronavirus disease 2019 (COVID-19) pandemic. This study aimed to provide a comprehensive view of the global distribution of asthma burden and its attributable risk factors from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study 2019 Database, asthma incidence, deaths, disability-adjusted life years (DALYs), the corresponding age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), age-standardized DALY rate, and estimated annual percentage change were analyzed according to age, sex, sociodemographic index (SDI) quintiles, and locations. Risk factors contributing to asthma deaths and DALYs were also investigated. RESULTS: Globally, the asthma incidence increased by 15%, but deaths and DALYs decreased. The corresponding ASIR, ASDR, and age-standardized DALY rate also decreased. The high SDI region had the highest ASIR, and the low SDI region had the highest ASDR. The ASDR and age-standardized DALY rate were negatively correlated with the SDI. The low-middle SDI region, particularly South Asia, showed the highest asthma-related deaths and DALYs. The incidence peak was under 9 years old, and more than 70% of all deaths occurred in the population over 60 years old. Smoking, occupational asthmagens, and a high body mass index were the main risk factors for asthma-related mortality and DALYs, and their distributions varied between sexes. CONCLUSIONS: Globally, the asthma incidence has increased since 1990. The greatest asthma burden is borne by the low-middle SDI region. The 2 groups that need special attention are those under 9 years old and those over 60 years old. Targeted strategies are needed to reduce the asthma burden based on geographic and sex-age characteristics. Our findings also provide a platform for further investigation into the asthma burden in the era of COVID-19.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Social isolation, loneliness and positive mental health among older adults in Canada during the COVID-19 pandemic. / Isolement social, solitude et santé mentale positive chez les aînés au Canada pendant la pandémie de COVID-19.

INTRODUCTION: Social isolation and loneliness are associated with poorer mental health among older adults. However, less is known about how these experiences are independently associated with positive mental health (PMH) during the COVID-19 pandemic. METHODS: We analyzed data from the 2020 and 2021 cycles of the Survey on COVID-19 and Mental Health to provide estimates of social isolation (i.e. living alone), loneliness and PMH outcomes (i.e. high self-rated mental health, high community belonging, mean life satisfaction) in the overall older adult population (i.e. 65+ years) and across sociodemographic groups. We also conducted logistic and linear regressions to separately and simultaneously examine how social isolation and loneliness are associated with PMH. RESULTS: Nearly 3 in 10 older adults reported living alone, and over a third reported feelings of loneliness due to the pandemic. When examined separately, living alone and loneliness were each associated with lower PMH. When assessed simultaneously, loneliness remained a significant independent factor associated with all three PMH outcomes (overall and across all sociodemographic groups), but living alone was only a significant factor for high community belonging in the overall population, for males and for those aged 65 to 74 years. CONCLUSION: Overall, social isolation and loneliness were associated with poorer wellbeing among older adults in Canada during the pandemic. Loneliness remained a significant factor related to all PMH outcomes after adjusting for social isolation, but not vice versa. The findings highlight the need to appropriately identify and support lonely older adults during (and beyond) the pandemic.

The Role of Surveillance Inspections in Reducing False-Positives of SARS-CoV-2 Omicron Variants during the COVID-19 Epidemic.

Objective: This study aims to assess the effectiveness of surveillance inspections conducted by the provincial health committee in Quanzhou city during a COVID-19 outbreak in reducing false-positive results in SARS-CoV-2 RT-PCR assays. Method: The team conducted on-site inspections of laboratories that participated in mass screening, recording any violations of rules. Results: The positive cases in five rounds of mass screening were 23, 173, and 4 in Licheng District, Fengze District, and Luojang District, respectively. The false-positive rates in the five rounds of mass screening were 0.0099%, 0.0063%, 0.0018%, 0.0006%, and 0%, respectively. The study also recorded that the number of violations in the seven selected laboratories was 36, 68, 69, 42, 60, 54 and 47. The corresponding false-positive rates were 0.0012%, 0.0060%, 0.0082%, 0.0032%, 0.0060%, 0.0027%, and 0.0021%, respectively. The study found a positive correlation between false-positive rates and the number of violations (r = 0.905, P=0.005), and an inverse correlation between false-positive rates and the frequency of surveillance inspections (r = -0.950, P < 0.001). Conclusion: Daily surveillance inspection in laboratories can remind laboratories to strictly comply with standard procedures, focus on laboratory quality control, and reduce the occurrence of false-positive cases in SARS-CoV-2 nucleic acid tests to some extent. This study recommends that government decision-making departments establish policies and arrange experts to conduct daily surveillance inspections to improve laboratory quality control.

Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial.

COVID-19 infection and vaccination offer disparate levels of defense against reinfection and breakthrough infection. This study was designed to examine the effects of curcumin supplementation, specifically HydroCurc (CURC), versus placebo (CON) on circulating inflammatory biomarkers in adults who had previously been diagnosed with COVID-19 and subsequently received a primary series of monovalent vaccine doses. This study was conducted between June 2021 and May 2022. Participants were randomized to receive CURC (500 mg) or CON capsules twice daily for four weeks. Blood sampling was completed at baseline and week-4 and analyzed for biomarkers. Linear regression was utilized to examine the between-group differences in post-trial inflammatory biomarker levels, adjusting for baseline and covariates including age, sex, race/ethnicity, and interval between COVID-19 diagnosis and trial enrollment. The sample (n = 31) was 71% female (Age 27.6 ± 10.4 y). The CURC group exhibited significantly lower post-trial concentrations of proinflammatory IL-6 (ß = -0.52, 95%CI: -1.03, -0.014, p = 0.046) and MCP-1 (ß = -0.12, 95%CI: -0.23, -0.015, p = 0.027) compared to CON, adjusting for baseline and covariates. Curcumin intake confers anti-inflammatory activity and may be a promising prophylactic nutraceutical strategy for COVID-19. These results suggest that 4 weeks of curcumin supplementation resulted in significantly lower concentrations of proinflammatory cytokines in adults who recovered from COVID-19 infection and were subsequently vaccinated.

Predominance of inhalation route in short-range transmission of respiratory viruses: Investigation based on computational fluid dynamics.

During the Coronavirus disease 2019 pandemic, short-range virus transmission has been observed to have a higher risk of causing infection than long-range virus transmission. However, the roles played by the inhalation and large droplet routes cannot be distinguished in practice. A recent analytical study revealed the predominance of short-range inhalation over the large droplet spray route as causes of respiratory infections. In the current study, short-range exposure was analyzed via computational fluid dynamics (CFD) simulations using a discrete phase model. Detailed facial membranes, including eyes, nostrils, and a mouth, were considered. In CFD simulations, there is no need for a spherical approximation of the human head for estimating deposition nor the "anisokinetic aerosol sampling" approximation for estimating inhalation in the analytical model. We considered two scenarios (with two spheres [Scenario 1] and two human manikins [Scenario 2]), source-target distances of 0.2 to 2 m, and droplet diameters of 3 to 1,500 µm. The overall CFD exposure results agree well with data previously obtained from a simple analytical model. The CFD results confirm the predominance of the short-range inhalation route beyond 0.2 m for expiratory droplets smaller than 50 µm during talking and coughing. A critical droplet size of 87.5 µm was found to differentiate droplet behaviors. The number of droplets deposited on the target head exceeded those exposed to facial membranes, which implies a risk of exposure through the immediate surface route over a short range. Electronic Supplementary Material ESM: the Supplementary Materials are available in the online version of this article at 10.1007/s12273-022-0968-y.

Whole genome sequence analysis of SARS-CoV-2 from 40 imported cases of confirmed COVID-19 in Sichuan

Objective: To understand the genomic characteristics of SARS-CoV-2 from 40 imported cases with confirmed COVID-19 in Sichuan during January and March 2022. Methods: Total viral RNA was extracted from respiratory samples of 182 confirmed COVID-19 cases who entered China through Chendu International Airport from January to March 2022. Mutation nucleic acid detection kit was used to identify the mutant strains and Illumina sequencing platform was applied for whole genome sequence(WGS) of virus. SARS-CoV-2 reference sequences were downloaded from NCBI database for genetic evolution and antigen variation analysis. The Nextclade and Pangolin online virus analysis platform were used to determine the virus family and type, and to analyze the mutation loci of the virus. The phylogenetic tree was constructed, along with the epidemiological data of cases to analyze the source and correlation of viruses. Results: Among 182 imported COVID-19 cases,B.1.617.2 mutations were identified in 3 cases and B.1.1.529 mutations were detected in 57 cases.A total of 40 SARS-CoV-2 whole genome sequences with coverage>95% were obtained in this study. Nextclade typing analysis showed that 3 sequences belonged to 21J(Delta),5 sequences belonged to 21K(Omicron)and the remaining 32 sequences belonged to 21L(Omicron). Pangolin typing analysis showed that the 3 sequences of 21J(Delta)belonged to AY.4,AY.109and B.1.617.2, the 5sequences of 21K(Omicron)all belonged to BA.1.1, and the remaining 32 sequences of 21L(Omicron)belonged to BA.2. Our sequence results were99.7% consistency with the Omicron variants sequences in current GISAID database. Compared with the reference sequence strain Wuhan-Hu-1(NC_045512.2),45,47and 42nucleotide variation sites and 36,25 and 36amino acid variation sites were found in the 3 sequences of 21J(Delta). There were average 59(26-64)nucleotide mutation sites and 48(10-53)amino acid mutation sites in the 5sequences of 21K(Omicron). The median number of nucleotide mutation sites of 71(66-76)and amino acid mutation sites of 53(40-56)were identified in the 32sequences of 21L(Omicron). Phylogenetic tree analysis showed that 40SARS-CoV-2WGSs were all related to the current variants of concern(VOC). Conclusions Continuous: sequencing of SARS-CoV-2whole genome from imported cases with confirmed COVID-19is of great significance for the prevention and control of the outbreak and prevalence of local epidemic caused by imported viruses in Sichuan.

Tracing the origin of large respiratory droplets by their deposition characteristics inside the respiratory tract during speech

Origin of differently sized respiratory droplets is fundamental for clarifying their viral loads and the sequential transmission mechanism of SARS-CoV-2 in indoor environments. Transient talking activities characterized by low (0.2 L/s), medium (0.9 L/s), and high (1.6 L/s) airflow rates of monosyllabic and successive syllabic vocalizations were investigated by computational fluid dynamics (CFD) simulations based on a real human airway model. SST k−ω model was chosen to predict the airflow field, and the discrete phase model (DPM) was used to calculate the trajectories of droplets within the respiratory tract. The results showed that flow field in the respiratory tract during speech is characterized by a significant laryngeal jet, and bronchi, larynx, and pharynx-larynx junction were main deposition sites for droplets released from the lower respiratory tract or around the vocal cords, and among which, over 90% of droplets over 5 µm released from vocal cords deposited at the larynx and pharynx-larynx junction. Generally, droplets' deposition fraction increased with their size, and the maximum size of droplets that were able to escape into external environment decreased with the airflow rate. This threshold size for droplets released from the vocal folds was 10–20 µm, while that for droplets released from the bronchi was 5–20 µm under various airflow rates. Besides, successive syllables pronounced at low airflow rates promoted the escape of small droplets, but do not significantly affect the droplet threshold diameter. This study indicates that droplets larger than 20 µm may entirely originate from the oral cavity, where viral loads are lower;it provides a reference for evaluating the relative importance of large-droplet spray and airborne transmission route of COVID-19 and other respiratory infections.

Response and duration of serum anti-SARS-CoV-2 antibodies induced by the third dose of an inactivated vaccine: A prospective longitudinal cohort study at 21 serial time points over 641 days.

Given the prevalence of low-pathogenic but highly infectious Omicron variants, a cohort study was conducted to assess the response and duration of novel coronavirus-inactivated vaccine-induced antibodies 1 year after the third dose (Day 641). Blood samples were collected and anti-spike neutralizing antibodies (neutralizing antibody), total antibodies against the receptor-binding domain of the spike protein (total antibody), and immunoglobulin G antibodies against the spike protein (IgG antibody) were determined. Antibody kinetics and attenuation were evaluated. The results showed that the levels of neutralizing, total, and IgG antibodies on Day 641 were 98.05 IU/mL, 152.8 AU/mL, and 7.68 S/CO, respectively. Levels of anti-SARS-CoV-2 antibodies were higher in the younger subgroup than in the older subgroup at several time points after the second and third doses. The seropositive rate of neutralizing antibodies providing protection from infection or severe infection was 46.87% and 87.5%, and the seropositive rates of total antibody and IgG antibody were maintained at 100% and 90.63%, respectively. The half-lives of neutralizing, total, and IgG antibodies were 186.89, 363.04, and 417.50 days, respectively. Collectively, anti-SARS-CoV-2 antibodies may provide a certain degree of protection from infection 1 year after the third dose and high protection from severe infection.

Protocol of a randomised controlled trial to assess medical staff's inhalation exposure to infectious particles exhaled by patients during oesophagogastroduodenoscopy and the efficacy of surgical masks in this context.

BACKGROUND: Aerosol-generating procedures such as oesophagogastroduodenoscopy (OGD) result in infectious particles being exhaled by patients. This substantially increases the medical staff's risk of occupational exposure to pathogenic particles via airway inhalation and facial mucosal deposition. Infectious particles are regarded as a key route of transmission of SARS-CoV-2 and, thus, represents a major risk factor for medical staff during the ongoing COVID-19 pandemic. There is a need for quantitative evidence on medical staff's risk of multiroute exposure to infectious particles exhaled by patients during OGD to enable the development of practical, feasible and economical methods of risk-reduction for use in OGD and related procedures. This randomised controlled trial (RCT)-Personal protective EquiPment intervention TrIal for oesophagogastroDuodEnoscopy (PEPTIDE)-aims to establish a state-of-the-art protocol for quantifying the multiroute exposure of medical staff to infectious particles exhaled by patients during real OGD procedures. METHOD AND ANALYSIS: PEPTIDE will be a prospective, two-arm, RCT using quantitative methods and will be conducted at a tertiary hospital in China. It will enrol 130 participants (65 per group) aged over 18. The intervention will be an anthropomorphic model with realistic respiratory-related morphology and respiratory function that simulates a medical staff member. This model will be used either without or with a surgical mask, depending on the group allocation of a participant, and will be placed beside the participants as they undergo an OGD procedure. The primary outcome will be the anthropomorphic model's airway dosage of the participants' exhaled infectious particles with or without a surgical mask, and the secondary outcome will be the anthropomorphic model's non-surgical mask-covered facial mucosa dosage of the participants' exhaled infectious particles. Analyses will be performed in accordance with the type of data collected (categorical or quantitative data) using SPSS (V.26.0) and RStudio (V.1.3.959). ETHICS AND DISSEMINATION: Ethical approval for this RCT was obtained from the Ethics Committee of Peking Union Medical College Hospital (ZS-3377). All of the potential participants who agree to participate will provide their written informed consent before they are enrolled. The results will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05321056.

Administration of macrolide antibiotics increases cardiovascular risk.

Background: The increased risk of cardiovascular events in patients prescribed macrolides has been subject to debate for decades. Methods: Medline, EMBASE databases and ClinicalTrials.gov were searched from inception until August 31, 2022 for studies investigating the link between macrolides and cardiovascular risk. A meta-analysis was performed using a random-effects model. Results: A total of 80 studies involving 39,374,874 patients were included. No association was found between macrolides and all-cause death. However, compared with the non-macrolide group, macrolides were associated with a significantly increased risk of ventricular arrhythmia or sudden cardiac death (VA or SCD) (azithromycin, relative ratio [RR]: 1.53; 95% confidence interval [CI]: 1.19 to 1.97; clarithromycin, RR: 1.52; 95% CI: 1.07 to 2.16). Besides, administration of macrolides was associated with a higher risk of cardiovascular disease (CVD) death (azithromycin, RR: 1.63; 95% CI: 1.17 to 2.27) and a slightly increased risk of myocardial infarction (MI) (azithromycin, RR: 1.08; 95% CI: 1.02 to 1.15). Interestingly, no association was observed between roxithromycin and adverse cardiac outcomes. Increased risk of VA or SCD was observed for recent or current use of macrolides, MI for former use, and CVD death for current use. Conclusion: Administration of macrolide antibiotics and timing of macrolide use are associated with increased risk for SCD or VTA and cardiovascular death, but not all-cause death.