Parenting and family self-sufficiency services contribute to impacts of Early Head Start for children and families.

Introduction: There is evidence that two-generation early childhood programs, those that strive to support not only child development, but also optimal parenting and family wellbeing, help to foster resilience for young children and their families in the face of adversity. Methods: Using data from a large experimental evaluation, the Early Head Start Research and Evaluation Project, this paper explores how parenting and family self-sufficiency services embedded in Early Head Start (EHS), a federally funded, nationally implemented two-generation early childhood program for low-income families lasting from pregnancy and until children are three, contribute to the impacts of the program for both the children and their families. Results: Parenting support in any modality (home visiting, case management or parent education) contributed to program impacts on important child and family outcomes, but not parent employment. Somewhat surprisingly, family receipt of employment services did not lead to any of the impacts of the program, while education and job training services did. When EHS parents received education or job training services, it led to impacts not only on mother employment, but also on other important family and child outcomes. Discussion: These findings validate and reinforce the two-generation approach of EHS, specifically supporting the focus on parenting and parent education and job training.

Reduced Left Atrial Rotational Flow Is Independently Associated With Embolic Brain Infarcts.

BACKGROUND: Up to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms. OBJECTIVES: This study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF. METHODS: The authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts. RESULTS: Patients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05). CONCLUSIONS: Reduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.

Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease.

BACKGROUND: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). METHODS: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). RESULTS: Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. CONCLUSIONS: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.

Smoking and COVID-19 outcomes: an observational and Mendelian randomisation study using the UK Biobank cohort.

BACKGROUND: Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity. METHODS: We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-19 outcomes were derived from Public Health England SARS-CoV-2 testing data, hospital admissions data, and death certificates (until 18 August 2020). Logistic regression was used to estimate associations between smoking status and confirmed SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death. Inverse variance-weighted MR analyses using established genetic instruments for smoking initiation and smoking heaviness were undertaken (reported per SD increase). RESULTS: There were 421 469 eligible participants, 1649 confirmed infections, 968 COVID-19-related hospitalisations and 444 COVID-19-related deaths. Compared with never-smokers, current smokers had higher risks of hospitalisation (OR 1.80, 95% CI 1.26 to 2.29) and mortality (smoking 1-9/day: OR 2.14, 95% CI 0.87 to 5.24; 10-19/day: OR 5.91, 95% CI 3.66 to 9.54; 20+/day: OR 6.11, 95% CI 3.59 to 10.42). In MR analyses of 281 105 White British participants, genetically predicted propensity to initiate smoking was associated with higher risks of infection (OR 1.45, 95% CI 1.10 to 1.91) and hospitalisation (OR 1.60, 95% CI 1.13 to 2.27). Genetically predicted higher number of cigarettes smoked per day was associated with higher risks of all outcomes (infection OR 2.51, 95% CI 1.20 to 5.24; hospitalisation OR 5.08, 95% CI 2.04 to 12.66; and death OR 10.02, 95% CI 2.53 to 39.72). INTERPRETATION: Congruent results from two analytical approaches support a causal effect of smoking on risk of severe COVID-19.

Independent effects of adiposity measures on risk of atrial fibrillation in men and women: a study of 0.5 million individuals.

BACKGROUND: Atrial fibrillation (AF) has a higher prevalence in men than in women and is associated with measures of adiposity and lean mass (LM). However, it remains uncertain whether the risks of AF associated with these measures vary by sex. METHODS: Among 477 904 UK Biobank participants aged 40-69 without prior AF, 23 134 incident AF cases were identified (14 400 men, 8734 women; median follow-up 11.1 years). Cox proportional hazards models were used to estimate the covariate adjusted hazard ratios (HRs) describing the association of AF with weight, measures of adiposity [fat mass (FM), waist circumference (WC)] and LM, and their independent relevance, by sex. RESULTS: Weight and WC were independently associated with risk of AF [HR: 1.25 (1.23-1.27) per 10 kg, HR: 1.11 (1.09-1.14) per 10 cm, respectively], with comparable effects in both sexes. The association with weight was principally driven by LM, which, per 5 kg, conferred double the risk of AF compared with FM when mutually adjusted [HR: 1.20 (1.19-1.21), HR: 1.10 (1.09-1.11), respectively]; however, the effect of LM was weaker in men than in women (p-interaction = 4.3 x 10-9). Comparing the relative effects of LM, FM and WC identified different patterns within each sex; LM was the strongest predictor for both, whereas WC was stronger than FM in men but not in women. CONCLUSIONS: LM and FM (as constituents of weight) and WC are risk factors for AF. However, the independent relevance of general adiposity for AF was more limited in men than in women. The relevance of both WC and LM suggests a potentially important role for visceral adiposity and muscle mass in AF development.

The impact of atrial fibrillation and stroke risk factors on left atrial blood flow characteristics.

AIMS: Altered left atrial (LA) blood flow characteristics account for an increase in cardioembolic stroke risk in atrial fibrillation (AF). Here, we aimed to assess whether exposure to stroke risk factors is sufficient to alter LA blood flow even in the presence of sinus rhythm (SR). METHODS AND RESULTS: We investigated 95 individuals: 37 patients with persistent AF, who were studied before and after cardioversion [Group 1; median CHA2DS2-VASc = 2.0 (1.5-3.5)]; 35 individuals with no history of AF but similar stroke risk to Group 1 [Group 2; median CHA2DS2-VASc = 3.0 (2.0-4.0)]; and 23 low-risk individuals in SR [Group 3; median CHA2DS2-VASc = 0.0 (0.0-0.0)]. Cardiac function and LA flow characteristics were evaluated using cardiac magnetic resonance. Before cardioversion, Group 1 displayed impaired left ventricular (LV) and LA function, reduced LA flow velocities and vorticity, and a higher normalized vortex volume (all P < 0.001 vs. Groups 2 and 3). After restoration of SR at ≥4-week post-cardioversion, LV systolic function and LA flow parameters improved significantly (all P < 0.001 vs. pre-cardioversion) and were no longer different from those in Group 2. However, in the presence of SR, LA flow peak and mean velocity, and vorticity were lower in Groups 1 and 2 vs. Group 3 (all P < 0.01), and were associated with impaired LA emptying fraction (LAEF) and LV diastolic dysfunction. CONCLUSION: Patients at moderate-to-high stroke risk display altered LA flow characteristics in SR in association with an LA myopathic phenotype and LV diastolic dysfunction, regardless of a history of AF.

Assessment of the causal relevance of ECG parameters for risk of atrial fibrillation: A mendelian randomisation study.

BACKGROUND: Atrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR). METHODS AND FINDINGS: Weighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87-0.96, P = 2 × 10-4 and OR 0.94; 95% CI: 0.93-0.96, P = 2 × 10-19, respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank. CONCLUSIONS: In UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.

Left atrial 4D flow cardiovascular magnetic resonance: a reproducibility study in sinus rhythm and atrial fibrillation.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows sophisticated quantification of left atrial (LA) blood flow, and could yield novel biomarkers of propensity for intra-cardiac thrombus formation and embolic stroke. As reproducibility is critically important to diagnostic performance, we systematically investigated technical and temporal variation of LA 4D flow in atrial fibrillation (AF) and sinus rhythm (SR). METHODS: Eighty-six subjects (SR, n = 64; AF, n = 22) with wide-ranging stroke risk (CHA2DS2VASc 0-6) underwent LA 4D flow assessment of peak and mean velocity, vorticity, vortex volume, and stasis. Eighty-five (99%) underwent a second acquisition within the same session, and 74 (86%) also returned at 30 (27-35) days for an interval scan. We assessed variability attributable to manual contouring (intra- and inter-observer), and subject repositioning and reacquisition of data, both within the same session (same-day scan-rescan), and over time (interval scan). Within-subject coefficients of variation (CV) and bootstrapped 95% CIs were calculated and compared. RESULTS: Same-day scan-rescan CVs were 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis, and were similar between SR and AF subjects (all p > 0.05). Interval-scan variability was similar to same-day scan-rescan variability for peak velocity, vorticity, and vortex volume (all p > 0.05), and higher for stasis and mean velocity (interval scan CVs of 14% and 8%, respectively, both p < 0.05). Longitudinal changes in heart rate and blood pressure at the interval scan in the same subjects were associated with significantly higher variability for LA stasis (p = 0.024), but not for the remaining flow parameters (all p > 0.05). SR subjects showed significantly greater interval-scan variability than AF patients for mean velocity, vortex volume, and stasis (all p < 0.05), but not peak velocity or vorticity (both p > 0.05). CONCLUSIONS: LA peak velocity and vorticity are the most reproducible and temporally stable novel LA 4D flow biomarkers, and are robust to changes in heart rate, blood pressure, and differences in heart rhythm.

The impact of a statewide trauma-informed child welfare initiative on children's permanency and maltreatment outcomes.

This article presents findings of a state-wide trauma informed child-welfare initiative with the goal of improving well-being, permanency and maltreatment outcomes for traumatized children. The Massachuetts Child Trauma Project (MCTP), funded by the Administration of Children and Families, Children's Bureau was a multi-year project implementing trauma-informed care into child welfare service delivery. The project's implementation design included training and consultation for mental health providers in three evidence-based treatments and training of the child-welfare workforce in trauma-informed case work practice. The learning was integrated between child-welfare and mental health with Trauma Informed Leadership Teams which included leaders from both systems and the greater community. These teams developed incremental steps toward trauma-informed system improvement. This study evaluated whether MCTP was associated with reductions in child abuse and neglect, improvements in placement stability, and higher rates of permanency during the first year of implementation. Children in the intervention group had fewer total substantiated reports of maltreatment, including less physical abuse and neglect than the comparison group by the end of the intervention year. However, children in the intervention group had more maltreatment reports (substantiated or not) and total out-of-home placements than did their counterparts in the comparison group. Assignment to MCTP, however, was not associated with an increase in kinship care or adoption. Overall, the results are promising in reinforcing the importance of mobilizing communities toward improvements in child-welfare service delivery.

It's not as simple as it sounds: Problems and solutions in accessing and using administrative child welfare data for evaluating the impact of early childhood interventions.

In recent years, there has been increasing interest in using administrative data collected by state child welfare agencies as a source of information for research and evaluation. The challenges of obtaining access to and using these data, however, have not been well documented. This study describes the processes used to access child welfare records in six different states and the approach to combining and using the information gathered to evaluate the impact of the Early Head Start program on children's involvement with the child welfare system from birth through age eleven. We provide "lessons learned" for researchers who are attempting to use this information, including being prepared for long delays in access to information, the need for deep understanding of how child welfare agencies record and code information, and for considerable data management work for translating agency records into analysis-ready datasets. While accessing and using this information is not easy, and the data have a number of limitations, we suggest that the benefits can outweigh the challenges and that these records can be a useful source of information for policy-relevant child welfare research.

The effect of Early Head Start on child welfare system involvement: A first look at longitudinal child maltreatment outcomes.

The high societal and personal costs of child maltreatment make identification of effective early prevention programs a high research priority. Early Head Start (EHS), a dual generational program serving low-income families with children prenatally through age three years, is one of the largest federally funded programs for infants and toddlers in the United States. A national randomized trial found EHS to be effective in improving parent and child outcomes, but its effectiveness in reducing child maltreatment was not assessed. The current study used administrative data from state child welfare agencies to examine the impact of EHS on documented abuse and neglect among children from seven of the original seventeen programs in the national EHS randomized controlled trial. Results indicated that children in EHS had significantly fewer child welfare encounters between the ages of five and nine years than did children in the control group, and that EHS slowed the rate of subsequent encounters. Additionally, compared to children in the control group, children in EHS were less likely to have a substantiated report of physical or sexual abuse, but more likely to have a substantiated report of neglect. These findings suggest that EHS may be effective in reducing child maltreatment among low-income children, in particular, physical and sexual abuse.