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Importance: Sudden infant death syndrome (SIDS) remains a leading cause of death during the first year of life. The etiology of SIDS is complex and remains largely unknown., Objective: To evaluate whether siblings of children who died of SIDS have a higher risk of SIDS compared with the general pediatric population., Design, Setting, and Participants: This register-based cohort study used Danish nationwide registers. Participants were all infants (<1 year) in Denmark between January 1, 1978, and December 31, 2016, including siblings of children who died of SIDS. Siblings were followed up from the index cases' date of SIDS, date of birth, or immigration, whichever came first, and until age 1 year, emigration, developing SIDS, death, or study end. The median (IQR) follow-up was 1 (1-1) year. Data analysis was conducted from January 2017 to October 2022., Main Outcomes and Measures: Standardized incidence ratios (SIRs) of SIDS were calculated with Poisson regression models relative to the general population., Results: In a population of 2 666 834 consecutive births (1 395 199 [52%] male), 1540 infants died of SIDS (median [IQR] age at SIDS, 3 [2-4] months) during a 39-year study period. A total of 2384 younger siblings (cases) to index cases (first sibling with SIDS) were identified. A higher rate of SIDS was observed among siblings compared with the general population, with SIRs of 4.27 (95% CI, 2.13-8.53) after adjustment for sex, age, and calendar year and of 3.50 (95% CI, 1.75-7.01) after further adjustment for mother's age (<29 years vs ≥29 years) and education (high school vs after high school)., Conclusions and Relevance: In this nationwide study, having a sibling who died of SIDS was associated with a 4-fold higher risk of SIDS compared with the general population. Shared genetic and/or environmental factors may contribute to the observed clustering of SIDS. The family history of SIDS should be considered when assessing SIDS risk in clinical settings. A multidisciplinary genetic evaluation of families with SIDS could provide additional evidence.

Objectives: To assess how biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids and disease activity affect risk of Staphylococcus aureus bacteraemia (SAB) in patients with rheumatoid arthritis (RA)., Methods: In a nationwide cohort of patients with RA from the DANBIO registry, we conducted a nested case-control study including first-time microbiologically verified SAB cases from 2010 to 2018 and incidence density matched controls (1:4 by sex, age). We interlinked Danish registries and identified antirheumatic treatments, RA-specific clinical characteristics, comorbidities and socioeconomic status. The relative risk of SAB was assessed by adjusted ORs with 95% CIs and number needed to harm (NNH) reflected the absolute risk., Results: Among 30 479 patients, we identified 180 SAB cases (incidence rate: 106.7/100 000 person-years) and matched 720 controls (57% women, median age 73 years, IQR: 65-80). Risk of SAB was increased in current (OR 1.8 (95% CI 1.1 to 3.2)) and former bDMARD users (OR 2.5 (95% CI 0.9 to 7.0)), and in current users of oral glucocorticoids ≤7.5 prednisolone-equivalent mg/day (OR 2.2 (95% CI 1.3 to 4.0) and >7.5 mg/day (OR 9.5 (95% CI 3.9 to 22.7)) (non-use as reference). ORs for moderate/high disease activity compared with remission were 1.6 (95% CI 0.8 to 3.3)/1.5 (95% CI 0.6 to 4.3). Risk was increased in patients with longstanding RA (>10 years vs ≤3 years, OR=2.4 (95% CI 1.1 to 5.3)). The NNH was 1172(95% CI 426 to 9374) for current use of bDMARDs and 110(95% CI 43 to 323) for glucocorticoids >7.5 mg/day., Conclusion: We identified a dose-dependent increased risk of SAB in patients with RA currently using oral glucocorticoids. Daily use of >7.5 mg appeared to be a clinically relevant risk factor, whereas the absolute risk was low for bDMARDs. No clear impact of disease activity was found., Competing Interests: Competing interests: SSD has received grants related to the submitted work from The Danish Rheumatism Association and Beckett-fonden. FM, MN, LBO and AP reports no disclosures. All outside the submitted work: TB reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, Astra Zeneca, Janssen, Pentabase ApS; CT-P reports grants from Novo Nordisk and Bayer; BG reports grants from Pfizer, BMS, Sandoz, and chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies, and; and Merete Hetland reports grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis; co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylarthritis based on secondary data and is partly funded by Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infective endocarditis (IE) is diagnosed in 7-8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs., Methods: In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3-10%, high-risk 10-30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3-10%), or "wait & see" (IE < 3%)., Results: We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to "wait & see" strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence., Conclusion: In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography., (© 2021. The Author(s).)

Background: Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs., Methods: We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE, and cardiac device., Results: Among 6506 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men) the IE prevalence was 7.1% (95% CI, 6.5-7.8). The lowest IE prevalence was found with Streptococcus pneumoniae ( S pneumoniae ) 1.2% (0.8-1.6) and Spyogenes 1.9% (0.9-3.3). An intermediary IE prevalence was found with Sanginosus 4.8% (3.0-7.3), Ssalivarius 5.8% (2.9-10.1), and Sagalactiae 9.1% (6.6-12.1). The highest IE prevalence was found with Smitis/oralis 19.4% (15.6-23.5), Sgallolyticus (formerly Sbovis ) 30.2% (24.3-36.7), Ssanguinis 34.6% (26.6-43.3), Sgordonii 44.2% (34.0-54.8), and Smutans 47.9% (33.3-62.8). In multivariable analysis using S pneumoniae as reference, all species except S pyogenes were associated with significantly higher IE risk, with the highest risk found with S gallolyticus odds ratio (OR) 31.0 (18.8-51.1), S mitis/oralis OR 31.6 (19.8-50.5), S sanguinis OR 59.1 (32.6-107), S gordonii OR 80.8 (43.9-149), and S mutans OR 81.3 (37.6-176)., Conclusions: The prevalence of IE in streptococcal BSIs is species dependent with S mutans, S gordonii, S sanguinis, S gallolyticus , and S mitis/oralis having the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.

Aims: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSIs). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE., Methods and Results: By crosslinking nationwide registries from 2010 to 2017, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. In total 69 021, distributed with 15 350, 16 726, 19 251, and 17 694 BSIs were identified in the periods of 2010-2011, 2012-2013, 2014-2015, and 2016-2017, respectively. Patients with E. faecalis had the highest prevalence of IE (16.7%) followed by S. aureus (10.1%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis and Streptococcus spp. increased significantly (P = 0.0005 and P = 0.03, respectively). Male patients had a higher prevalence of IE for E. faecalis, Streptococcus spp., and CoNS compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age., Conclusion: For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction: Staphylococcus aureus bacteremia (SAB) is an invasive infection with high mortality and morbidity. Rheumatoid arthritis (RA) is associated with increased risk of infections due to the disease per se and the use of antirheumatic treatments. Few minor studies have previously investigated risk of SAB in patients with RA and indicated increased risk compared with the general population. This nationwide observational study aims to investigate incidence of and risk factors for SAB in adult patients with RA compared with the general population. The effect of disease characteristics (eg, joint erosions, disease duration and activity), different antirheumatic treatments and smoking on SAB risk will be evaluated., Methods and Analysis: All adults (>18 years of age) alive and living in Denmark in 1996-2017 will be identified in The Danish Civil Registration System. Incident patients with RA are identified in the Danish National Patient Registry (DNPR) and the nationwide rheumatology registry, DANBIO, in which information on, for example, antirheumatic treatments, disease characteristics and smoking is collected prospectively in routine care. Information on comorbidities, invasive procedures and prescribed drugs are identified in the DNPR and in The Register of Medicinal Product Statistics. Socioeconomic status is evaluated in national registers on income and education. Incident cases of first-time SAB are identified in The Danish National SAB Database. All registers are linked on an individual level by unique civil registration numbers. Incidence rates and incidence rate ratios will be analysed using Poisson regression models and the impact of possible risk factors will be evaluated., Ethics and Dissemination: All data will be handled in accordance with the General Data Protection Regulation (EU) 2016/679. No ethical approval is necessary in Denmark when handling registry data only. The results will be presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology initiative in international peer-reviewed journals and at medical conferences., Trial Registration Number: NCT03908086., Competing Interests: Competing interests: TB reports grants from Pfizer, grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants from GSK, personal fees from Pfizer, and BG reports grants from Pfizer, Biogen and Abbvie, all outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: It is known that patients surviving infective endocarditis have a poor long-term prognosis; however, few studies have addressed the long-term causes of death in patients surviving the initial hospitalization., Methods: Using Danish administrative registries, we identified patients admitted to a hospital with 1st time infective endocarditis in the period from January 1996 to December 2014, who were alive at the time of discharge. The study population was categorized into (i) patients undergoing medical therapy only and (ii) patients undergoing surgical and medical treatment. We examined the cardiovascular and non-cardiovascular causes of death. Using the Cox analysis, we investigated the associated risk of dying from a specific prespecified cause of death (heart failure, infective endocarditis and stroke) within the surgery group when compared with the medically treated group., Results: We identified 5576 patients: 4220 patients belonged to the medically treated group and 1356 patients to the surgery group. At the 10-year follow-up, the mortality rate was 63.1% and 41.6% in the medically treated group and the surgery group, respectively. Cardiovascular disease was the most frequent cause of death in both groups accounting for 52.5% in the medically treated group and 55.2% in the surgery group. Patients undergoing surgery were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients [hazard ratio = 0.66 (95% confidence interval: 0.46-0.94) and hazard ratio = 0.59 (95% confidence interval: 0.37-0.96), respectively]., Conclusions: No major differences were found in the main causes of death between groups. Patients in the surgical group were associated with a lower risk of dying from heart failure and stroke when compared with medically treated patients.

Background: The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis., Methods: Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models., Results: One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996-2012 and 2002-2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70-4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02-1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54-3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78-5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death., Conclusion: All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

Background: Staphylococcus aureus bacteremia (SAB) is the leading cause of infective endocarditis in several countries. Since socioeconomic status (SES) is known to influence the risk of infectious diseases in general, we aimed to investigate the association between SES and SAB, and risk of subsequent endocarditis in a nationwide adult population., Methods: All Danish residents were consecutively included at age ≥ 30 years during 1996-2010. We obtained information on SES (highest attained educational level), comorbidities, and microbiologically verified SAB by cross-linking nationwide registries. The incidence rate ratios (IRRs) of SAB and later endocarditis were investigated using Poisson regression models adjusted for sex, age and year (reference = highest SES)., Results: Our study population comprised 3,394,936 individuals (median age = 43.2 years). Over a median follow-up of 15.9 years, 13,181 individuals acquired SAB. SES was inversely associated with SAB acquisition, which declined with increasing age, e.g. in individuals with lowest SES, IRRs were 3.78 (95% confidence interval [CI] = 2.89-4.95) in age 30-50 years, 1.87 (CI = 1.60-2.18) in age > 50-70 years and 1.31 (CI = 1.11-1.54) in age > 70 years (interaction-p < 0.0001). Adjustment for comorbidities attenuated the IRRs, but the pattern persisted. No association between SES and endocarditis risk among patients with SAB was observed., Conclusions: Decreasing SES was associated with an increased risk of SAB, particularly in younger adults. SES was not associated with risk of subsequent endocarditis.