Borderline Interaction Research Articles

Potential association between obstructive lung diseases and cognitive decline.

Chronic obstructive lung diseases, such as asthma and COPD, appear to have a more extensive impact on overall functioning than previously believed. The latest data from clinical trials suggests a potential link between cognitive deterioration and chronic obstructive inflammatory lung disease. This raises the question of whether these diseases affect cognitive functions and whether any relevant biomarker may be identified. This prospective observational study included 78 patients divided equally into asthma, COPD, and control groups (n=26, 27 and 25 respectively). The participants underwent identical examinations at the beginning of the study and after at least 12 months. The test battery comprised 16 questionnaires (11 self-rated, 5 observer-rated, assessing cognition and mental state), spirometry, and blood samples taken for PKA and CREB mRNA evaluation. A 2.3-fold increase in CREB mRNA was observed between examinations (p=0.014) for all participants; no distinctions were observed between the asthma, COPD, and control groups. Pooled, adjusted data revealed a borderline interaction between diagnosis and CREB expression in predicting MMSE (p=0.055) in COPD, CREB expression is also associated with MMSE (β=0.273, p=0.034) like with the other conducted tests (β=0.327, p=0.024) from COPD patients. No correlations were generally found for PKA, although one significant negative correlation was found between the first and second time points in the COPD group (β=-0.4157, p=0.049),. Chronic obstructive lung diseases, such as asthma and COPD, may have some linkage to impairment of cognitive functions. However, the noted rise in CREB mRNA expression might suggest a potential avenue for assessing possible changes in cognition, especially in COPD; such findings may reveal additional transcription factors linked to cognitive decline.

The association between metal exposure and body mass index of preschool children of Shaanxi, China

There are few studies on the association between polymetallic exposure and obesity in preschool children, and the conclusions are inconsistent. The study aimed to explore the association between urine metals and body mass index (BMI). For 342 preschool children in the industrial park of Shaanxi, China, uniformly trained investigators collected basic information of preschoolers and measured height and weight. Morning urine were collected, and BMI were calculated. We measured concentrations of 22 urine metals by quadrupole inductively coupled plasma-mass spectrometry (ICP-MS).The least absolute shrinkage and selective operator (LASSO) regression model was used to screen urine metals larger impact on BMI. In the polymetallic exposure model, generalized linear regression was used to explore the relationship between the selected urine metals and BMI. The overall relationship between urine metals and BMI was analyzed using restricted cubic spline (RCS). The interaction method was used to explore the influence of metal-metal interaction on BMI. After adjustment for covariates, ln-transformed urinary copper (Cu) levels and urinary molybdenum (Mo) levels were negatively associated with BMI, (Cu, β=−1.219, 95% CI: −2.047, −0.391, P<0.05; Mo, β=−0.797, 95% CI: −1.508, −0.087, P<0.05). Polymetallic model showed similar results. Both ln-transformed urinary Cu levels and urinary Mo levels were negatively correlated with BMI (Cu: β=−1.556, 95% CI: −2.488, −0.624, P<0.05; Mo: β=−0.915, 95% CI: −1.817, −0.013, P<0.05). The results of RCS visually demonstrate that Cu and BMI are non-linearly correlated (Ptotal < 0.001, Pnonliearity = 0.005), Mo and BMI are linearly correlated (Ptotal < 0.05, Pnonliearity = 0.099) Urinary Cu was negatively correlated with BMI nonlinearly in preschool children, and there was a borderline interaction between urinary Mo and Cu levels.Further researches are needed to validate these associations and reveal underlying mechanisms

Potential interplay between tumor size and vitamin D receptor (VDR) polymorphisms in breast cancer prognosis: a prospective cohort study.

Vitamin D has some anticancer properties that may decrease breast cancer risk and improve prognosis. The aim was to investigate associations between four previously studied VDR SNPs (Taq1, Tru91, Bsm1, and Fok1) and prognosis in different groups of breast cancer patients. VDR genotyping of 1,017 breast cancer patients included 2002-2012 in Lund, Sweden, was performed using Oncoarray. Follow-up was until June 30, 2019. Clinical data and patient information were collected from medical records and questionnaires. Cox regression was used for survival analyses. Genotype frequencies were as follows: Fok1 (AA 15.7%, AG 49.1%, GG 35.1%), Bsm1 (CC 37.2%, CT 46.1%, TT 16.7%), Tru91 (CC 77.8%, CT 20.7%, TT 1.5%), and Taq1 (AA 37.2%, AG 46.2%, GG 16.6%). During follow-up there were 195 breast cancer events. The homozygous variants of Taq1 and Bsm1 were associated with reduced risk of breast cancer events (adjusted HR = 0.59, 95% CI 0.38-0.92 for Taq1 and adjusted HR = 0.61, 95% CI 0.40-0.94 for Bsm1). The G allele of the Fok1 was associated with increased risk of breast cancer events in small tumors (pT1, adjusted HR = 1.83, 95% CI 1.04-3.23) but not in large tumors (pT2/3/4, adjusted HR = 0.80, 95% CI 0.41-1.59) with a borderline interaction (Pinteraction = 0.058). No interactions between VDR genotypes and adjuvant treatments regarding breast cancer prognosis were detected. VDR genotypes were associated with breast cancer prognosis and the association might be modified by tumor size. Further research is needed to confirm the findings and elucidate their potential clinical implications.

The Interaction of Dietary Patterns and Genetic Variants on the Risk of Cardiovascular Diseases in Chinese Patients with Type 2 Diabetes.

Diabetes is an important risk factor for cardiovascular disease (CVD), which in turn is the most common and serious complication of diabetes. This study analyzes dietary patterns and single nucleotide polymorphisms (SNPs) in 543 diabetes patients with new-onset cardiovascular events and 461 diabetic patients without. SNPs are determined and analyzed using real time PCR and gene chip method. Factor analysis and logistic regression are used to determine dietary patterns and evaluate the level of associations and interaction effects, respectively. The legumes and edible fungi pattern and vegetable pattern show a significant negative correlation with complication risk. ADIPOQ rs37563 and legumes and edible fungi pattern have a significant interactive effect on disease, and patients with a high score of C polymorphism genotype (GC+CC) have a lower risk of disease. 5-10-Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and vegetable pattern have a borderline interaction effect on disease, and those patients with TT genotype have a lower risk of disease. These findings provide new insights into the role of the interactive protection of dietary patterns and SNPs. And participants with specific alleles show a lower risk of cardiovascular complications.

SERUM COPEPTIN AS A PROGNOSTIC MARKER IN PRE-ECLAMPSIA

Objective: Pre-eclampsia (PE) is as a risk factor for subsequent cardiovascular and kidney disease. Serum copeptin correlates with adverse kidney outcomes in the general population and is increased during PE as compared to healthy pregnancy. We describe the association between copeptin and subsequent kidney outcomes in pregnant women. Design and method: We enrolled 372 patients with PE and 82 with healthy pregnancy in this prospective cohort study. Serum copeptin was measured at 6 weeks post-partum (PP). Office blood pressure (BP), eGFR and albuminuria were measured at 6 weeks as well as at 1 year PP in a sub-group of 110 patients. Interaction effect was tested using likelihood ratio test (LRT). Results: As compared to healthy controls, patients with PE were less frequently Caucasian, more likely smokers and had higher body mass index (p &lt; 0.05). At 6 weeks PP, copeptin levels were similar between groups. At one year PP, systolic BP (SBP), diastolic BP (DBP) and albuminuria were higher in PE as compared to control patients (p &lt; 0.05) while eGFR was similar between groups. A significant interaction existed between copeptin and PE status regarding DBP at 1 year PP (p = 0.045 for LRT). A similar but borderline interaction existed between copeptin and PE status for albuminuria at 1 year PP (p = 0.126 for LRT). Conclusions: At 6 weeks PP, women who suffered from PE do not have increased copeptin levels as compared to healthy controls. However, in case of PE only, copeptin levels are associated with subsequent adverse kidney outcome. Whether this association is causal and would represent a potential therapeutic target remains to be tested.

Antithrombotic monotherapy for stable coronary artery disease and atrial fibrillation patients with and without prior coronary artery revascularization: Insights from the AFIRE trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Japan Cardiovascular Research Foundation under a contract with Bayer Yakuhin Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial demonstrated that rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban plus a single antiplatelet therapy regarding efficacy and superior for safety endpoints in patients with atrial fibrillation and stable coronary artery disease including patients not requiring revascularization [prior percutaneous coronary intervention (PCI) or bypass grafting (CABG)]. Purpose The aim of this post-hoc subgroup analysis was to investigate the efficacy and safety of rivaroxaban monotherapy compared to combination therapy in patients with and without prior revascularization. Methods Among 2,215 patients included in the modified intention-to-treat analysis in the AFIRE trial, 1445 patients (65.2%) had undergone previous PCI alone, and 252 (11.4%) had undergone previous CABG. The remaining 518 patients (23.4%) was categorized as a group without prior revascularization and then compared with a group with prior revascularization (PCI or CABG). The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis. Results In 1697 patients with prior revascularization, efficacy and safety endpoints of rivaroxaban monotherapy were superior to combination therapy (efficacy: HR 0.62, 95%CI 0.45-0.85, p=0.003; safety: HR 0.62, 95%CI 0.39-0.98, p=0.040), whereas there were no significant differences in efficacy and safety endpoints among 518 patients without prior revascularization (efficacy: HR 1.19, 95%CI 0.67-2.11, p=0.553; safety: HR 0.47, 95%CI 0.18-1.26, p=0.125). There was a borderline interaction of efficacy endpoint (P for interaction=0.055) by randomized treatment assignment (Figure 1 and Figure 2). Compared with combination therapy, the safety benefit of rivaroxaban monotherapy on any bleeding was significant in patients without prior revascularization (HR 0.59, 95%CI 0.38-0.93, p=0.022). Conclusions In patients with prior PCI or CABG, rivaroxaban monotherapy resulted in more favorable safety and efficacy outcomes than combination therapy. There was a borderline interaction for primary efficacy outcome between prior revascularization and anti-thrombotic therapy.

Leisure-Time Physical Activity Has a More Favourable Impact on Carotid Artery Stiffness Than Vigorous Physical Activity in Hypertensive Human Beings.

Aim. To assess the effect of leisure time versus vigorous long-term dynamic physical activity (PA) on carotid stiffness in normotensive versus hypertensive subjects. Methods. The study was conducted on 120 leisure-time exercisers and 120 competitive athletes. One hundred and twenty sedentary subjects served as controls. In addition, participants were classified according to whether their systolic blood pressure was ≥130 mmHg (hypertensives, n = 120) or normal (normotensives, n = 240) according to the ACC/AHA 2017 definition. Carotid artery stiffness was assessed with an echo-tracking ultrasound system, using the pressure-strain elastic modulus (EP) and one-point pulse wave velocity (PWVβ) as parameters of stiffness. Results. The effect of the two levels of PA differed in the normotensives and the hypertensives. Among the normotensives, there was an ongoing, graded reduction in EP and PWVβ from the sedentary subjects to the athletes. By contrast, among the hypertensives, the lowest levels of EP and PWVβ were found among the leisure-time PA participants. EP and PWVβ did not differ between the hypertensive sedentary subjects and the athletes. A significant interaction was found between PA and BP status on EP (p = 0.03) and a borderline interaction on PWVβ (p = 0.06). In multiple regression analyses, PA was a negative predictor of EP (p = 0.001) and PWVβ (p = 0.0001). The strength of the association was weakened after the inclusion of heart rate in the models (p = 0.04 and 0.007, respectively). Conclusions. These data indicate that in people with hypertension, leisure-time PA has beneficial effects on carotid artery stiffness, whereas high-intensity chronic PA provides no benefit to vascular functions.

Colchicine and Quality of Life in Patients With Acute Coronary Syndromes: Results From the COPS Randomized Trial

BackgroundRecent data suggest that colchicine may reduce cardiovascular events among patients presenting with acute coronary syndromes. This sub-study of the Australian COPS trial aimed to assess whether colchicine affects health status outcomes. MethodsHealth status was assessed at baseline and 12-months using the EuroQol-5 Dimension 5-level (EQ-5D-5L) score and the full 19-question Seattle Angina Questionnaire (SAQ). Data were available for 786 patients (388 randomized to colchicine, 398 to placebo). ResultsBaseline characteristics were well matched between groups; mean age was 60.1 (SD 14.8) years, and 20 % were female. Baseline health status scores were impaired, and most parameters demonstrated significant improvement from baseline to 12-months (EQ-5D-5L Visual Analogue Score [VAS] 69.3 to 77.7; SAQ angina frequency score 83.0 to 95.3, both p < 0.001). No significant differences in adjusted mean score change among any of the EQ-5D-5L or SAQ dimensions were observed between treatment groups in either intention-to-treat or per-protocol analysis. There were borderline interactions in EQ-5D-5L scores for those with previous MI vs not, and in SAQ scores for those with obesity vs not. In categorical analysis using observed data, patients treated with colchicine were more likely to have clinically significant improvement in physical limitation score over the period (36 % improved vs. 28 %, p < 0.05). Baseline health status scores were not associated with the primary endpoint at 12 months. ConclusionsTreatment with colchicine did not appear to affect change in measures of health status following acute coronary syndromes, but it did lead to a greater likelihood of improvement in physical limitation scores. Trial registrationACTRN, ACTRN12615000861550. Registered 18/08/2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368973.

Activity of regorafenib in patients with non-adipocytic soft tissue sarcoma (NASTS): Evaluation of heterogeneity of treatment effect on the updated analysis of pooled cohorts.

11555 Background: Results of the double-blind randomized phase 2 trial (NCT01900743), showed that regorafenib (REG) is an active treatment in patients (pts) previously treated with chemotherapy for an NASTS (cohorts B-leiomyosarcoma, C-synovial sarcoma, D-other sarcoma, Mir 2016), and in pts previously treated with pazopanib (PAZ) (cohort E, Penel 2019). We now present an updated analysis of progression-free survival (PFS) in all NASTS pts to assess the heterogeneity of treatment effect according to histological subtype and prior exposure to PAZ. Methods: Pts received REG 160 mg/d, 21/28 d, or placebo (PB). Pts receiving PB were offered optional cross over in case of centrally confirmed disease progression. The primary endpoint was PFS, according to RECIST-1.1, based on full blinded central review of imaging (including a re-review for cohorts B, C and D, because first analysis was based on a partial central review in these cohorts). Overall survival (OS) was a secondary endpoint. We performed a pooled analysis of cohorts B, C, D and E, on the intent-to-treat dataset, including a multivariate analysis with interaction terms to assess the heterogeneity of treatment effect according to covariates. Results: From 06/2013 to 10/2017, 175 pts were randomized (87 REG vs 88 PB; 56, 27, 55, 37 pts in cohorts B, C, D and E, respectively). The median age was 59 yrs (range, 20-81). There were 101 women (58%). Histological subtype was leiomyosarcoma in 80 pts (LMS; 41 REG vs 39 PB; 56 in cohort B and 24 in cohort E), synovial sarcoma in 28 (SS; 13 REG vs 15 PB; 27 in cohort C and 1 in cohort E), and other sarcoma in 67 (33 REG vs 34 PB; 55 in cohort D and 12 in cohort E). The median number of prior lines of systemic treatment was 2 (range, 1-6). Overall, 43 pts had received prior PAZ (21 REG vs 22 PB). Out of 88 pts assigned to PB, 69 switched to REG after progression (79%). We confirmed a significant PFS-benefit associated with REG in multivariate analysis of the pooled study population, with a HR = 0.48 (95%CI, 0.35–0.66, p &lt; 0.001); median PFS = 2.1 vs 1.0 months, respectively. This benefit appears significant in each histological subtype. However, we observed a borderline interaction between histological subtype and treatment effect (p = 0.09): PFS benefit appears larger in pts with SS (HR = 0.21, 0.10-0.48, p &lt; 0.001) and other sarcoma (HR = 0.49, 0.30-0.81, p = 0.006) than in LMS (HR = 0.59, 0.37-0.93, p = 0.022). PFS benefit appears rather homogeneous across strata of pts with vs without prior exposure to PAZ (interaction test, p = 0.26). Overall, in this study, regorafenib does not show any statistically significant OS-benefit (HR = 0.77, 0.57–1.05, p = 0.10), likely due to the fact that 79% of PB pts crossed over to REG at progression. Conclusions: The present study confirms the clinical PFS benefit associated with regorafenib in all NASTS pts, regardless of prior treatment with pazopanib. Clinical trial information: NCT01900743.

Prenatal androgenization causes expression changes of progesterone and androgen receptor mRNAs in the arcuate nucleus of female mice across development.

Prenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS). In prenatally androgenised (PNA) mice, a model of PCOS, progesterone receptor (PR) protein expression is reduced in arcuate nucleus (ARC) GABA neurons. This suggests a mechanism for PCOS-related impaired steroid hormone feedback and implicates androgen excess with respect to inducing transcriptional repression of the PR-encoding gene Pgr in the ARC. However, the androgen sensitivity of ARC neurons and the relative gene expression of PRs over development and following prenatal androgen exposure remain unknown. Here, we used a quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) of microdissected ARC to determine the relative androgen receptor (Ar) and progesterone receptor (Pgr) gene expression in PNA and control mice at five developmental timepoints. In a two-way analysis of variance, none of the genes examined showed expression changes with a statistically significant interaction between treatment and age, although PgrA showed a borderline interaction. For all genes, there was a statistically significant main effect of age on expression levels, reflecting a general increase in expression with increasing age, regardless of treatment. For PgrB and Ar, there was a statistically significant main effect of treatment, indicating a change in expression following PNA (increased for PgrB and decreased for Ar), regardless of age. For PgrA, there was a borderline main effect of treatment, suggesting a possible change in expression following PNA, regardless of age. PgrAB gene expression changes showed no significant main effect of treatment. We additionally examined androgen and progesterone responsiveness specifically in P60 ARC GABA neurons using RNAScope® (Advanced Cell Diagnostics, Inc.) in situ hybridization. This analysis revealed that Pgr and Ar were expressed in the majority of ARC GABA neurons in normal adult females. However, our RNAScope® analysis did not show significant changes in Pgr or Ar expression within ARC GABA neurons following PNA. Lastly, because GABA drive to gonadotropin-releasing hormone neurons is increased in PNA, we hypothesised that PNA mice would show increased expression of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA production. However, the RT-qPCR showed that the expression of GAD encoding genes (Gad1 and Gad2) was unchanged in adult PNA mice compared to controls. Our findings indicate that PNA treatment can impact Pgr and Ar mRNA expression in adulthood. This may reflect altered circulating steroid hormones in PNA mice or PNA-induced epigenetic changes in the regulation of Pgr and Ar gene expression in ARC neurons.

Colchicine and quality of life in patients with acute coronary syndromes: results from the COPS randomized trial

Abstract Background Recent data suggest that colchicine may reduce cardiovascular events among patients presenting with acute coronary syndromes. This sub-study of the Australian COPS trial aimed to assess whether colchicine affects health status outcomes. Methods Health status was assessed at baseline and 12-months using the EuroQol-5 Dimension 5-level (EQ-5D-5L) score and the full 19-question Seattle Angina Questionnaire (SAQ). Data were available for 786 patients (388 randomized to colchicine, 398 to placebo). Results Baseline characteristics were well matched between groups; mean age was 60.1 (SD 14.8) years, and 20% were female. Baseline health status scores were impaired, and most parameters demonstrated significant improvement from baseline to 12-months (EQ-5D-5L Visual Analogue Score [VAS] 69.3 to 77.7; SAQ angina frequency score 83.0 to 95.3, both p&amp;lt;0.001). No significant differences in adjusted mean score change among any of the EQ-5D-5L or SAQ dimensions were observed between treatment groups in either intention-to-treat or per-protocol analysis. There were borderline interactions in EQ-5D-5L scores for those with previous MI vs not, and in SAQ scores for those with obesity vs not. In categorical analysis using observed data, patients treated with colchicine were more likely to have clinically significant improvement in physical limitation score over the period (36% improved vs. 28%, P&amp;lt;0.05). Baseline health status scores were not associated with the primary endpoint at 12 months. Conclusions Treatment with colchicine did not appear to affect change in measures of health status following acute coronary syndromes, but it did lead to a greater likelihood of improvement in physical limitation scores. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Peninsula Health, Monash University

Childhood adversities, late-life stressors and the onset of depressive symptoms in community-dwelling older adults

Objective: Depression is common in older individuals though many factors associated with its occurrence remain under-researched. We examined whether childhood adversities (CAs) and late-life stressors are associated with the onset of depressive symptoms in adults aged ≥ 65 and if these early- and late-life stressors interact in the prediction of depressive symptoms. Methods: Data came from the 2010 and 2013 waves of the Japan Gerontological Evaluation Study (JAGES) (N = 8701). The Geriatric Depression Scale (GDS-15) was used to assess the presence of depressive symptoms (GDS ≥ 5). A Poisson regression analysis was used to examine associations. Results: Both CAs (1 event: incidence rate ratio [IRR] = 1.59, 95% confidence interval [CI]: 1.41–1.79; ≥ 2 events: IRR = 2.36, 95% CI = 1.80–3.10) and late-life stressful events (1 event: IRR = 1.13, 95% CI: 1.02–1.25; ≥ 2 events: IRR = 1.25, 95% CI = 1.05–1.50) were significantly associated with the onset of depressive symptoms. Borderline significant interactions between CAs and late-life stressors (e.g. ≥ 2 CAs and ≥ 2 late-life events: IRR = 0.61, p = 0.087) suggest that late-life stressors may be important in predicting the onset of depressive symptoms especially among individuals with no or fewer CAs compared to those with ≥ 2 CAs. Conclusions: Stressful events in childhood and late adulthood were independently associated with the onset of depressive symptoms in older adults. In addition, stressful experiences in childhood might affect how individuals respond to stressful events in later life.

A Non-APOE Polygenic Risk Score for Alzheimer's Disease Is Associated With Cerebrospinal Fluid Neurofilament Light in a Representative Sample of Cognitively Unimpaired 70-Year Olds.

The effect of Alzheimer’s disease (AD) polygenic risk scores (PRS) on amyloid and tau pathophysiology and neurodegeneration in cognitively unimpaired older adults is not known in detail. This study aims to investigate non-APOE AD-PRS and APOE ε4 in relation to AD pathophysiology evaluated by cerebrospinal fluid (CSF) biomarkers in a population-based sample of 70-year olds. A total of 303 dementia-free individuals from the Gothenburg H70 Birth Cohort Studies were included. Genotyping was performed using the NeuroChip, and AD-PRS were calculated. CSF levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), neurogranin (Ng), and neurofilament light (NfL) were measured with enzyme-linked immunosorbent assay. Associations were found between non-APOE PRS and both NfL (p = .001) and Aβ42 (p = .02), and between APOE ε4 and Aβ42 (p = 1e−10), t-tau (p = 5e−4), and p-tau (p = .002). Similar results were observed when only including individuals with CDR = 0, except for no evidence of an association between non-APOE PRS and Aβ42. There was an interaction between non-APOE PRS and Aβ42 pathology status in relation to NfL (p = .005); association was only present in individuals without Aβ42 pathology (p = 3e-4). In relation to Aβ42, there was a borderline interaction (p = .06) between non-APOE PRS and APOE ε4; association was present in ε4 carriers only (p = .03). Similar results were observed in individuals with CDR = 0 (n = 246). In conclusion, among cognitively healthy 70-year olds from the general population, genetic risk of AD beyond the APOE locus was associated with NfL in individuals without Aβ42 pathology, and with Aβ42 in APOE ε4 carriers, suggesting these associations are driven by different mechanisms.

Ecological correlates of Spanish preschoolers’ physical activity and sedentary behaviours during structured movement sessions

From an ecological perspective that understands health behaviours to be the result of interactions between personal, psychosocial and environmental factors, different authors have described patterns and correlations between physical activity (PA) and sedentary behaviours (SB) in physical education (PE). However, to our knowledge there have been no systematic evaluations of the PA levels and patterns during structured movement sessions in preschool children in Spain. Therefore, the aims of this study were: (a) to identify the individual, social and environmental factors that influence PA levels and patterns during structured movement sessions; (b) to assess PA and SB levels during these sessions in a preschool population in our country; and (c) to validate the use of the System for Observing Fitness Instruction Time (SOFIT) in Spanish preschoolers to assess PA and SB levels, using accelerometry as the reference method. Our major findings were that: (a) young children were physically active for more than 60% of the structured movement sessions; (b) boys were significantly more active than girls; (c) the lesson context of free play was associated with low levels of SB; (d) solitary and borderline interaction patterns during structured movement sessions significantly increased moderate- to vigorous-intensity PA; (e) social interaction was generally between the same gender; and (f) teachers spent most of the time observing. This study also provides an argument for reconsidering the responsibilities of early childhood education institutions and practitioners in developing structured PA opportunities in the framework of free exploration and communication.

Predictors of Mortality by Sex and Race in Heart Failure With Preserved Ejection Fraction: ARIC Community Surveillance Study.

BackgroundHeart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all‐cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study.Methods and ResultsAdjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1‐year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06–1.52 [P=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64–0.97 [P=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race.ConclusionsIn a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex‐ and race‐based differences in predictors of mortality may help strategize targeted management of HFpEF.

Lugar de acceso y tipo de anticoagulante en pacientes con síndrome coronario agudo en clase Killip avanzada o con parada cardiaca extrahospitalaria

Introduction and objectivesPatients who are vulnerable to hemodynamic or electrical disorders (VP) are often excluded from clinical trials and data on the optimal access-site or antithrombotic treatment are limited. We assessed outcomes of transradial vs transfemoral access and bivalirudin vs unfractionated heparin (UFH) in VP with acute coronary syndrome undergoing invasive management. MethodsThe MATRIX trial randomized 8404 patients to radial or femoral access and 7213 patients to bivalirudin or UFH. Among them, 934 (11.1%) were deemed VP due to advanced Killip class (n = 808), cardiac arrest (n = 168), or both (n = 42). The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE: death, myocardial infarction, or stroke) and net adverse clinical events (NACE: MACE or major bleeding). ResultsMACE and NACE were similarly reduced with radial vs femoral access in VP and non-VP. Transradial access was also associated with consistent relative benefits in all-cause and cardiovascular mortality or Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding with greater absolute benefits in VP. The effects of bivalirudin vs UFH on MACE and NACE were consistent in VP and non-VP. Bivalirudin was associated with lower all-cause and cardiovascular mortality in VP but not in non-VP, with borderline interaction testing. Bivalirudin reduced bleeding in both VP and non-VP with a larger absolute benefit in VP. ConclusionsIn acute coronary syndrome patients undergoing invasive management, the effects of randomized treatments were consistent in VP and non-VP, but absolute risk reduction with radial access and bivalirudin were greater in VP, with a 5- to 10-fold lower number needed to treat for benefits.Trial registry number: NCT01433627.

Choice of access site and type of anticoagulant in acute coronary syndromes with advanced Killip class or out-of-hospital cardiac arrest

Introduction and objectivesPatients who are vulnerable to hemodynamic or electrical disorders (VP) are often excluded from clinical trials and data on the optimal access-site or antithrombotic treatment are limited. We assessed outcomes of transradial vs transfemoral access and bivalirudin vs unfractionated heparin (UFH) in VP with acute coronary syndrome undergoing invasive management. MethodsThe MATRIX trial randomized 8404 patients to radial or femoral access and 7213 patients to bivalirudin or UFH. Among them, 934 (11.1%) were deemed VP due to advanced Killip class (n = 808), cardiac arrest (n = 168), or both (n = 42). The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE: death, myocardial infarction, or stroke) and net adverse clinical events (NACE: MACE or major bleeding). ResultsMACE and NACE were similarly reduced with radial vs femoral access in VP and non-VP. Transradial access was also associated with consistent relative benefits in all-cause and cardiovascular mortality or Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding with greater absolute benefits in VP. The effects of bivalirudin vs UFH on MACE and NACE were consistent in VP and non-VP. Bivalirudin was associated with lower all-cause and cardiovascular mortality in VP but not in non-VP, with borderline interaction testing. Bivalirudin reduced bleeding in both VP and non-VP with a larger absolute benefit in VP. ConclusionsIn acute coronary syndrome patients undergoing invasive management, the effects of randomized treatments were consistent in VP and non-VP, but absolute risk reduction with radial access and bivalirudin were greater in VP, with a 5- to 10-fold lower number needed to treat for benefits.Trial registry number: NCT01433627.

Association Between Perceived Neighborhood Characteristics and Carotid Artery Intima-Media Thickness: Cross-Sectional Results From the ELSA-Brasil Study

BackgroundLiving in a neighborhood with a low socioeconomic context may increase the risk of coronary heart disease. However, few studies have explored the impact of neighborhood characteristics on subclinical atherosclerosis, and their role as a risk factor for cardiovascular disease has not yet been studied in poor countries. ObjectivesThis study aimed to investigate the association between perceived neighborhood characteristics and subclinical atherosclerosis in a large sample of adults, using cross-sectional data from the ELSA-Brasil (Brazilian Longitudinal Study of Adult Health). MethodsParticipants free of clinical coronary artery disease answered a questionnaire designed to assess their perceptions regarding 6 neighborhood dimensions: social cohesion, walkability, availability of healthy food, safety, witnessed violence, and personal victimization. The scores of each domain were used as independent variables. Common carotid intima-media thickness (CCIMT) was used as a dependent variable. Then linear regression models, adjusted by demographic, socioeconomic, and cardiovascular factors, were used. ResultsA total of 9,923 adults (mean age = 51.5 ± 8.9 years, 44% male, 55% white) were examined. In the univariate analysis, better walkability (β = −0.62, 95% confidence interval [CI]: −1.01 to −0.23; p = 0.002) and low witnessed violence (β = −1.95; 95% CI: −2.96 to -0.94; p < 0.0001) were associated with lower CCIMT, whereas low personal victimization was associated with higher CCIMT (β = 10.70; 95% CI: 4.55 to 16.85; p = 0.001). A borderline interaction between neighborhood domain and sex was found. Better social cohesion may be associated with larger CCIMT among women, whereas better safety was associated with lower CCIMT among men. Multiple imputation for missing CCIMT data showed similar results. ConclusionsThe perception of living in a more walkable environment and in a neighborhood where people witness fewer violent episodes can provide protection on the early phases of the atherosclerosis process. Less stress and the practice of physical activity may explain the protection.

Social interaction patterns, therapist responsiveness, and outcome in treatments for borderline personality disorder.

Inflexible social interaction patterns are defining features of borderline personality disorder (BPD). Specific beliefs about the self and others may be activated across interaction situations, often leading to instable relationships. It may be pivotal to address these difficulties in early treatment phases, through appropriate therapist responsiveness, which means an adaptation of therapist's activity to their client's behaviours using emerging information in the process (Stiles, 2009, Clinical Psychology: Science and Practice, 16, 86). In this process-outcome study, responsiveness is operationalized by the motive-oriented therapeutic relationship (Caspar, 2007, Handbook of psychotherapeutic case formulations, 2nd ed., 251-289, Guilford), based on the Plan analysis case formulation. The present study assesses the interplay between social interaction problems and therapist responsiveness, explaining symptoms at discharge and the therapeutic alliance. In total, N=50 clients with BPD entered the study, and standard and responsive treatments were compared. Social interaction patterns were assessed by the newly developed Borderline Interaction Patterns Scale (BIPS), applied to recorded material of three sessions per therapy. Outcome was measured by general symptoms (OQ-45), borderline symptoms (BSL-23), interpersonal problems (IIP), and the therapeutic alliance (WAI). Results suggest that in standard treatment, social interaction patterns are neither related to outcome nor the therapeutic alliance. In responsive treatment, more activation of social interaction patterns predicted better outcome on IIP and lower therapist ratings of the alliance. The conclusions seem promising for specific effectiveness of responsive treatments in particular in the interpersonal problem area of BPD. Identifying social interaction patterns early in treatment may be a crucial pathway to change for BPD. Responsive therapy activating social interaction patterns may be crucial for better outcome. Future research should focus on mechanisms of change in early treatment phases for BPD. New scale for assessing social interaction patterns specific to borderline personality disorder.

The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C).

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.