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BACKGROUND: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). METHODS: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. RESULTS: Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for

Background: Takotsubo syndrome (TS) is an acute heart failure condition that presents with symptoms similar to acute myocardial infarction. TS is often triggered by emotional or physical stress and is an important cause of morbidity and mortality but predictors of mortality in TS patients are not well understood. There is a need to identify high-risk patients and tailor treatment accordingly. Purpose: The purpose of this study was to assess the importance of various clinical factors in predicting 30-day mortality in TS patients using a machine-learning algorithm capable of identifying complex relationships between variables. Methods: We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry for all TS patients between 2015-2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TS patients. Results: Of the 3,180 hospitalized TS patients, 76% were women. The average age was 68.3 ± 11.2 years. The crude all-cause mortality rate was 2.57% at 30 days. The most important variable in predicting 30-day mortality was the hospital where the patient was treated, with a relative importance of 35.5%. This was followed by the clinical presentation for angiography (21.1%), creatinine level (11.9%), Killip class (8.9%), and age at angioplasty (6.5%). Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia, smoking status, and hypertension. Gender and previous stroke history had a low impact on 30-day mortality in TS patients. Conclusions: The treating hospital was the most important factor in predicting 30-day mortality in TS. Since the level of evidence for recommended treatments of TS is low, our findings highlight the importance of conducting randomized studies in this patient group to improve care., The Swedish Heart and Lung Foundation, the Swedish Research Council, the Swedish state under the agreement between the Swedish government and the county councils (the ALF-agreement)

Background: The COVID-19 pandemic resulted in severe psychological, social, and economic stress. Countries applied different anti-pandemic strategies that substantially impacted citizens' psychosocial stress and health. Takotsubo syndrome (TS) is frequently triggered by emotional stress. Previous studies from the USA have reported a severalfold increase in TS incidence during pandemics. Purpose: To determine the incidence and outcomes of TS in Sweden before (2015-March 2020) and during (April 2020-December 2022) the pandemic. Methods: We assessed the incidence rate ratio (IRR) for all patients with TS referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry. Incidence rate ratios (IRRs) before and during the pandemic were calculated with Poisson regression adjusted for age and sex. We evaluated mortality with multivariable Cox proportional hazards regression, which accounted for clustering of patients within hospitals. The following variables were used for adjustment: age, sex, diabetes, smoking status, hypertension, hyperlipidemia, previous myocardial infarction, and Killip class. Results: We identified 3,180 patients (2,128 [76.0%] women) hospitalized with TS during the study period; 2,189 (69%) pre-pandemic and 991 (31%) during the pandemic. The average age was 68.3 ± 11.2 years. The median follow-up time was 1250 days (IQR 562-1995). The crude all-cause mortality rate was 2.57% at 30 days and 15.5% after long-term follow-up. The incidence of TS was 11% lower during the pandemic compared with the pre-pandemic period (IRR 0.90, 95% CI 0.83-0.98, P=0.009, Fig. 1). We found no difference in 30-day mortality (adjusted HR 1.12, 95% CI 0.69-1.78, P= 0.642) or long-term mortality (adjusted HR 0.96, 95% CI 0.73-1.28, P= 0.816) among patients with TS between the pre-pandemic and pandemic periods. When only data after 2016 are used, we found no difference in TS incidence (IRR 1.00, 95% CI 0.92-1.08, P=1.00). Con, Funding agencies:The Swedish Heart and Lung Foundation, the Swedish Research Council, the Swedish state under the agreement between the Swedish government and the county councils (the ALF-agreement).

Background: Current evidence suggests that use of intracoronary imaging during percutaneous coronary intervention (PCI) of the left main coronary artery (LMCA) reduces mortality. However, there is a scarcity of data on the overall role of intracoronary imaging, particularly in other non-LMCA proximal coronary artery lesions. We aimed to investigate the association of use of intracoronary imaging on outcome in proximal lesions treated with PCI. Methods: The Swedish Coronary Angiography and Angioplasty Registry was used to identify all proximal coronary artery lesions treated with stent implantation between June 11, 2013, and January 16, 2021. Proximal coronary artery lesions (LMCA, proximal left anterior descending artery, left circumflex artery, and right coronary artery) assessed by intracoronary imaging before and/or after stent implantation were matched to control lesions treated based on angiography alone using propensity score matching. The primary end point was target lesion revascularization with PCI, and secondary end points included all-cause mortality and definite stent thrombosis within 3 years. Results: Among the 3623 matched pairs, intracoronary imaging was associated with significantly lower risk of target lesion revascularization, 3.7% vs 4.7%; hazard ratio (HR), 0.77; 95% CI, 0.61-0.97; P = .025, and all-cause mortality, 9.1% vs 12.8%; HR, 0.70; 95% CI, 0.61-0.81; P < .001, with no difference in definite stent thrombosis. Conclusions: The use of intracoronary imaging in proximal coronary artery lesions is associated with lower rates of repeat revascularization and better survival. The results appear to be primarily driven by improved outcome of LMCA lesions. These results reinforce the role of intracoronary imaging in assessing and treating proximal coronary lesions., This work was supported by The Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, ALF, Skane University Hospital funds, Märta Winkler Foundation, Thorsten Westerströms Foundation,and the Anna-Lisa and Sven-Eric Lundgren Foundation for Medical Research.

Background: Deferral of coronary revascularization is safe whether guided by instantaneous wave-free ratio (iFR) or by fractional flow reserve (FFR). We aimed to assess long-term outcomes in patients deferred from revascularization based on iFR or FFR in a large real-world population. Methods: From 2013 through 2017, 201,933 coronary angiographies were registered in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). We included all patients (n = 11,324) with at least 1 coronary lesion deferred from PCI during an index procedure using iFR (>0.89; n = 1998) or FFR (>0.80; n = 9326). The primary outcome was major adverse cardiac events (MACE) defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. A multivariable-adjusted Cox proportional hazards model was used, with analysis for interaction of prespecified subgroups. Results: Patients presented with stable angina pectoris (iFR 46.9% vs FFR 48.6%), unstable angina or non–ST-elevation myocardial infarction (iFR 37.7% vs FFR 33.1%), ST-elevation myocardial infarction (iFR 1.9% vs FFR 1.6%), and other indications (iFR 12.5% vs FFR 15.7%). The median follow-up was 2 years for both iFR and FFR groups. At the conclusion of the study, the cumulative MACE risks were 26.7 for the iFR group and 25.9% for FFR group. In the adjusted analysis, no difference was found between the 2 groups (adjusted hazard ratio: iFR vs FFR, 0.947; 95% CI, 0.84-1.08; P = 39). Consistent with the overall findings, the prespecified subgroups showed no interaction with the FFR/iFR results. Conclusions: Deferral of revascularization showed similar long-term safety whether based on iFR or on FFR.

While the first part of the scientific statement on the pathophysiology of Takotsubo syndrome was focused on catecholamines and the sympathetic nervous system, in the second part we focus on the vascular pathophysiology including coronary and systemic vascular responses, the role of the central and peripheral nervous systems during the acute phase and abnormalities in the subacute phase, the gender differences and integrated effects of sex hormones, genetics of Takotsubo syndrome including insights from microRNA studies and inducible pluripotent stem cell models of Takotsubo syndrome. We then discuss the chronic abnormalities of cardiovascular physiology in survivors, the limitations of current clinical and preclinical studies, the implications of the knowledge of pathophysiology for clinical management and future perspectives and directions of research.

Background: The SWEDEHEART quality index of hospitals’ adherence to the evidence-based (EB) guidelines for myocardial infarction (MI) patients has been continuously used for several decades in Sweden. The grading protocol is based on the consensus among hospitals. The hospitals are awarded points (0, 0.5, 1) for each of the 11 indicators depending on the proportion of patients who received EB treatment and achieved treatment goals. The 11 indicators at present are reperfusion treatment in STEMI (yes/no), time to-reperfusion treatment in STEMI, time to revascularisation in NSTEMI, P2Y12 antagonists at discharge, ACE-inhibitor/ARB at discharge, the proportion of patients at follow-up, smoking cessation at one-year, participation in a physical exercise program, target LDL-cholesteroland target blood pressure at one year. Purpose: To evaluate whether the SWEDEHEART quality index predicts mortality in patients with MI. Methods: We used data for all MI patients reported to the SWEDEHEAR Tregistry from 72 hospitals in Sweden between 2015–2021. We calculated the difference in quality index between 2021 and 2015. The hospitals were divided into quintiles based on the difference in the score. Logistic regression with log-time offset was used to adjust for confounders (age, gender, diabetes, hypertension, hyperlipidemia, STEMI/NSTEMI, cardiac arrest before admission, occupation status, history of heart failure, prior MI, prior PCI, prior CABG, cardiogenic shock). Results: We identified 98,635 patients with MI, 32,608 (33.1%) were women and 34,198 (34.7%) had STEMI. The average age was 70.8±12.2 years. The median follow-up time was 2.7 years (IQR 1.06–4.63). The crude all-cause mortality rate was 5.5% at 30-days and 22.3% after long-term follow-up. Most hospitals (72.1%) improved their quality index on average by 3.4% per year (P<0.001). The increase in the quality index continued during COVID-19 pandemic (2020–2021) with average increase of 8.6%, 95% CI, 0.97–1.02; P<0.0

During settlement, migrant youth negotiate between various transitional spaces, which include educational, mediated and transnational spaces. To what extent can critical media literacy education acknowledge and strengthen young migrants’ resilience? In this article, we evaluate the Netherlands-based participatory action research project Critical media literacy through making media. Gathered empirical data include participant observation in two classes, in-depth interviews with 3 teachers and 19 students, as well an 18-minute film reflection. The focus is on how understandings, procedures and affectivity shape young migrants’ mindful media literacy practice. In order to develop media literacy education which works for all, we need to move away from a one-size-fits-all model based on the norms of Western, educated, industrialized, rich and democratic societies. Drawing on our experiences of co-creating, practicing and evaluating a curriculum with teachers and migrant students, we demonstrate the urgency of situated, reflexive, flexible, culture and context-aware critical media literacy education.

Background We aimed to study the effect of social containment mandates on ACS presentation during COVID-19 pandemic using location activity and mobility data from mobile phone map services. Methods We conducted a cross-sectional study using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) including all ACS presentations during the pandemic until 7 May 2020. Using a count regression model, we adjusted for day of the week, daily weather and incidence of COVID-19. Results A 10% increase in activity around areas of residence was associated with 38% lower rates of ACS hospitalizations, whereas increased activity relating to retail and recreation, grocery stores and pharmacies, workplaces and mode of mobility was associated with 10-20% higher rates of ACS hospitalizations. Conclusion Government policy regarding social containment mandates has important public health implications for medical emergencies such as ACS and may explain the decline in ACS presentations observed during COVID-19 pandemic., Funding Agencies|Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation Funding Source: Medline; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation Funding Source: Medline; Swedish Scientific Research CouncilSwedish Research Council Funding Source: Medline; ALF Funding Source: Medline; SSF (TOTAL-AMI) Funding Source: Medline; Bundy Academy Funding Source: Medline; Skane University Hospital Funds Funding Source: Medline; Marta Funding Source: Medline

Background Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. Objectives To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. Results 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. Conclusions Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis., Funding Agencies|Swedish HeartLung FoundationSwedish Heart-Lung Foundation [HLF20160688, HLF20180187]; Stockholm County CouncilStockholm County Council [K 20174577]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [HLF20180287]

OBJECTIVE: To determine whether infants who have regulatory problems (eg, sleeping, crying, and feeding problems) at 1 year of age are at increased risk of experiencing language difficulties at ages 5 and 11 years, compared with settled infants. STUDY DESIGN: Parent survey and child assessment data (n = 1131) were drawn from a longitudinal community cohort study. Latent Class Analysis identified 5 profiles of infant regulation including those who were settled (37%), had tantrums (21%), had sleep problems (25%), were moderately unsettled (13%), and severely unsettled (3%) at 12 months of age. Adjusted regression analyses examined associations between infant regulatory profiles and language ability (Clinical Evaluation of Language Fundamentals-fourth edition) at ages 5 and 11 years. RESULTS: Infants who were moderately unsettled had lower language scores at age 5 (adjusted mean difference, -3.89; 95% CI, -6.92 to -0.86) and were more likely to have language difficulties (aOR, 2.71; 95% CI, 1.28-5.75), than infants who were settled. Infants who were severely unsettled at 12 months of age, had lower language scores at ages 5 (adjusted mean difference, -7.71; 95% CI, -13.07 to -2.36) and 11 (adjusted mean difference, -6.50; 95% CI, -11.60 to -1.39), than infants who were settled. Severely unsettled infants were 5 times more likely to have language difficulties at age 5 than their settled counterparts (aOR, 5.01; 95% CI, 1.72-14.63). CONCLUSIONS: Children at 1 year of age with multiple regulatory problems are at an increased risk for poorer language skills at ages 5 and 11 years.

Objective: To evaluate the long-term efficacy of three currently available drug coated balloons (DCB) for the treatment of de-novo coronary lesions. Methods: This was a retrospective analysis of prospectively collected data from the Swedish Coronary Angiography and Angioplasty Registry. Between 2009 and 2017, three currently available DCB brands used in the treatment of de novo lesions were included. Outcomes were dinically driven restenosis and target lesion thrombosis (TLT) (per device) and major adverse cardiac events (MACE) including death, myocardial infarction or target vessel revascularization (per patient) at 4 years. Multivariable Cox regression models were used to adjust for differences. Results: We included 6715 lesions treated with DCBs, 4483 SeQuent (R) Please (S-DCB), 1071 IN.PACT Falcon (I-DCB) and 1161 Pantera (R) Lux (P-DCB), in 5670 patients. The mean DCB diameter was 2.4 mm. Bailout stenting occurred in 6.7% of lesions. Angiographic success was 98.5%. The overall cumulative rate of restenosis was 5.5% (299 events). The risk for reported restenosis did not significantly differ between l-DCB vs S-DCB, adjusted hazard ratio (aHR) 0.96; 95% confidence interval (CI) 0.69-1.34, P-DCB vs S-DCB aHR 0.88; 95% CI 0.63-123 and I-DCB vs P-DCB aHR 1.10; 95% CI 0.72-1.68. The cumulative risk for TLT was 0.8% in all three DCBs. The risk for MACE or individual components of MACE did not differ between the three patient-groups. Conclusion: In de novo coronary lesions, we found comparable long-term efficacy with three currently available DCB brands. DCB angioplasty was feasible with low risk for long-term restenosis and TLT.

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Background: Intracoronary pressure wire measurements of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) provide decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the impact of FFR/iFR on long-term clinical outcomes in patients with stable angina, unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), or STEMI. Methods: We used data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) on all patients in Sweden undergoing PCI (with or without FFR/iFR guidance) for stable angina, UA/NSTEMI, or STEMI between January 2005 and March 2018. The primary endpoint was all-cause mortality and the secondary endpoints were stent thrombosis or restenosis and periprocedural complications. The primary model was multilevel Cox proportional-hazards regression using an instrumental variable (IV) to adjust for known and unknown confounders with treating hospital as a treatment-preference instrument. The following variables were entered into Cox proportional-hazards regression in addition to the IV: age, sex, diabetes, indication for PCI, severity of coronary disease, smoking status, hypertension, hyperlipidemia, previous myocardial infarction, previous PCI, previous coronary artery bypass graft, type of stent. Results: In total, 151,001 patients underwent PCI: 31,514 (20.9%) for stable angina, 74,982 (49.6%) for UA/NSTEMI, and 44,505 (29.5%) for STEMI. Of these, FFR/iFR guidance was used in 11,433 patients (7.6%): 5029 (44.0%) with stable angina, 5989 (52.4%) with UA/NSTEMI, and 415 (3.6%) with STEMI; iFR was used in 1156 (10.1%) of these patients. After a median follow-up of 1784 (range 1–4824) days, the FFR/iFR group had lower adjusted risk estimates for all-cause mortality [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.91; P=0.001] and stent thrombosis and restenosis (HR 0.13; 95% CI 0.09–0.19; P<0.001). The number of periprocedural complications did, Funding Agency:ALF Västra Götaland

Aim: To evaluate utilization and outcomes of rotational atherectomy (RA) using data from the Swedish Coronary and Angioplasty Registry (SCAAR). Methods: We included 1476 patients with 2218 lesions who underwent RA from 2005 to 2016. To study temporal changes, the study period was divided into three equal time-periods, period A, B and C. Results: Although the number of RA procedures increased 3-fold from 2005 to 2016, the rate of RA (of all PCI procedures) remained low (0.5% vs 1.2% in 2005 vs 2016). RA patients consisted a high-risk group, with advanced age and clustering of comorbidities. Over time, included patients were older and had a higher risk profile. Trans-radial access, drug eluting stent (DES) use and use of intravascular imaging significantly increased from period A to C whereas positioning of a temporary pacemaker or intra-aortic balloon pump declined. Unfractionated heparin became the main anticoagulant (52 vs 87%) and use of glycoprotein IIb/IIIa inhibitors declined (31 vs 12%, in period A vs C). Following RA, 11% of lesions were treated without stent (15 vs 15 vs 8%, in period A, B and C) (Rota-only). In lesions treated with a stent, a bare metal stent (BMS) was implanted in 39% vs 12% vs 2% and a new generation DES (N-DES) in 5 vs 75 vs 97% (period A vs B vs C) of lesions. The 3-year cumulative rate of restenosis was 6.7% (122 events), (11.1 vs 7.1 vs 4.1% in period A vs B vs C). As compared to DES, rota-only (adjusted HR 2.71; 95% CI 1.69- 4.36) and BMS (adjusted HR 3.63; 95% CI 2.27- 5.81) were associated with significantly higher risk for restenosis. First generation DES were associated with numerically higher but not significantly different risk for restenosis as compared to N-DES (adjusted HR 1.31; 95% CI 0.74- 2.31). The 3 year cumulative rate of major adverse cardiac events (MACE), including death, myocardial infarction (MI) or any restenosis was 30.6% (34.2 vs 31.4 vs 28.2%, in period A vs B vs C) and the corresponding numbers for all-cause