Venous and arterial thrombosis in patients with VEXAS syndrome.

ABSTRACT: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, is an autoinflammatory disorder with diverse systemic manifestations. Thrombosis is a prominent clinical feature of VEXAS syndrome. The risk factors and frequency of thrombosis in VEXAS syndrome are not well described, due to the disease's recent discovery and the paucity of large databases. We evaluated 119 patients with VEXAS syndrome for venous and arterial thrombosis and correlated their presence with clinical outcomes and survival. Thrombosis occurred in 49% of patients, mostly venous thromboembolism (VTE; 41%). Almost two-thirds of VTEs were unprovoked, 41% were recurrent, and 20% occurred despite anticoagulation. The cumulative incidence of VTE was 17% at 1 year from symptom onset and 40% by 5 years. Cardiac and pulmonary inflammatory manifestations were associated with time to VTE. M41L was positively associated specifically with pulmonary embolism by univariate (odds ratio [OR]: 4.58, confidence interval [CI] 1.28-16.21, P = .02) and multivariate (OR: 16.94, CI 1.99-144.3, P = .01) logistic regression. The cumulative incidence of arterial thrombosis was 6% at 1 year and 11% at 5 years. The overall survival of the entire patient cohort at median follow-up time of 4.8 years was 88%, and there was no difference in survival between patients with or without thrombosis (P = .8). Patients with VEXAS syndrome are at high risk of VTE; thromboprophylaxis should administered be in high-risk settings unless strongly contraindicated.

Shape-constrained deformable brain segmentation: Methods and quantitative validation.

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions.

Artificial intelligence of arterial Doppler waveforms to predict major adverse outcomes among patients with diabetes mellitus.

OBJECTIVE: Patients with diabetes mellitus (DM) are at increased risk for peripheral artery disease (PAD) and its complications. Arterial calcification and non-compressibility may limit test interpretation in this population. Developing tools capable of identifying PAD and predicting major adverse cardiac event (MACE) and limb event (MALE) outcomes among patients with DM would be clinically useful. Deep neural network analysis of resting Doppler arterial waveforms was used to detect PAD among patients with DM and to identify those at greatest risk for major adverse outcome events. METHODS: Consecutive patients with DM undergoing lower limb arterial testing (April 1, 2015-December 30, 2020) were randomly allocated to training, validation, and testing subsets (60%, 20%, and 20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict all-cause mortality, MACE, and MALE at 5 years using quartiles based on the distribution of the prediction score. RESULTS: Among 11,384 total patients, 4211 patients with DM met study criteria (mean age, 68.6 ± 11.9 years; 32.0% female). After allocating the training and validation subsets, the final test subset included 856 patients. During follow-up, there were 262 deaths, 319 MACE, and 99 MALE. Patients in the upper quartile of prediction based on deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.31-5.56), MACE (HR, 2.06; 95% CI, 1.49-2.91), and MALE (HR, 13.50; 95% CI, 5.83-31.27). CONCLUSIONS: An artificial intelligence enabled analysis of a resting Doppler arterial waveform permits identification of major adverse outcomes including all-cause mortality, MACE, and MALE among patients with DM.

Children's empathy moderates the association between perceived interparental conflict and child health.

Interparental conflict is known to negatively impact child well-being, including behavioral and physiological well-being. Children's empathy - that is, vicariously experiencing others' emotions - may increase children's sensitivity to and the biological repercussions of interparental conflict. Although empathy represents a valued trait and is an important part of socioemotional development, its influence on children's physical health is unknown. This study examined whether empathy moderates the association between perceived interparental conflict and both child systemic inflammation and parent-rated overall child health in a sample of children between the ages of seven to nine. Children and their parents participating in the long-term evaluation of the Family Foundations program, a randomized trial of a perinatal preventative intervention, provided data approximately eight years following enrollment into the program. We collected peripheral blood samples via dried blood spots, anthropometric measurements, and child and parent psychosocial questionnaires. Results indicated significant positive main effects of child empathy on both C-reactive protein (CRP; B = 0.26, SE = 0.11, p =.026) and Interleukin-6 (IL-6; B = 0.20, SE = 0.10, p =.045) levels. Further, child affective empathy moderated the associations between perceived interparental conflict and both CRP (B = 0.39, SE = 0.19, p =.050) and parent-reported child health (B = 0.30, SE = 0.13, p =.021), such that greater empathy strengthened the negative associations between interparental conflict and child health. Overall, findings suggests that there may be a biological cost of being more empathic in high-conflict environments and highlight the need for tools to help more empathic children appropriately manage vicarious emotions.

Kindergarten conduct problems are associated with monetized outcomes in adolescence and adulthood.

BACKGROUND: Across several sites in the United States, we examined whether kindergarten conduct problems among mostly population-representative samples of children were associated with increased criminal and related (criminal + lost offender productivity + victim; described as criminal + victim hereafter) costs across adolescence and adulthood, as well as government and medical services costs in adulthood. METHODS: Participants (N = 1,339) were from two multisite longitudinal studies: Fast Track (n = 754) and the Child Development Project (n = 585). Parents and teachers reported on kindergarten conduct problems, administrative and national database records yielded indexes of criminal offending, and participants self-reported their government and medical service use. Outcomes were assigned costs, and significant associations were adjusted for inflation to determine USD 2020 costs. RESULTS: A 1SD increase in kindergarten conduct problems was associated with a $21,934 increase in adolescent criminal + victim costs, a $63,998 increase in adult criminal + victim costs, a $12,753 increase in medical services costs, and a $146,279 increase in total costs. In the male sample, a 1SD increase in kindergarten conduct problems was associated with a $28,530 increase in adolescent criminal + victim costs, a $58,872 increase in adult criminal + victim costs, and a $144,140 increase in total costs. In the female sample, a 1SD increase in kindergarten conduct problems was associated with a $15,481 increase in adolescent criminal + victim costs, a $62,916 increase in adult criminal + victim costs, a $24,105 increase in medical services costs, and a $144,823 increase in total costs. CONCLUSIONS: This investigation provides evidence of the long-term costs associated with early-starting conduct problems, which is important information that can be used by policymakers to support research and programs investing in a strong start for children.

Promoting toddlers' self-regulation and healthy eating habits among families living in poverty: A randomized controlled trial of Recipe 4 Success.

The Recipe 4 Success preventive intervention targeted multiple factors critical to the health and well-being of toddlers living in poverty. This randomized controlled trial, which was embedded within Early Head Start home visits for 12 weeks, included 242 racially and ethnically diverse families (51% girls; toddler mean age = 2.58 years; data collected 2016-2019). Compared to parents in usual practice home visits, parents in Recipe 4 Success displayed greater sensitive scaffolding of toddlers' learning and more responsive food parenting practices (Cohen's d = .21-.30). Toddlers in Recipe 4 Success exhibited greater self-regulation and had healthier eating habits (Cohen's d = |.16-.35|). Results highlight the value of Recipe 4 Success in promoting parent and toddler behavior change that could have life-long benefits.

Reduced calf muscle pump function is a risk factor for venous thromboembolism: a population-based cohort study.

The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P < .001) and unilateral (P < .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.

Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

BACKGROUND: Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. METHODS: Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). RESULTS: Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. CONCLUSION: iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.

Venous thromboembolism after COVID-19 vaccination in patients with thrombophilia.

Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Resource dilution in maternal feeding practices after birth of a secondborn.

Firstborn children have higher prevalence of obesity than secondborn siblings. The birth of a sibling typically results in resource dilution when mothers begin to divide their time and attention between two children. This mixed-methods analysis applies the family systems process of resource dilution to test the hypothesis that characteristics of the secondborn impact how parents feed the firstborn. Participants (n = 76) were mothers of consecutively born firstborn and secondborn siblings who participated in the INSIGHT trial and an observational cohort. Quantitative analyses involved multilevel models to test if characteristics of secondborns (temperament at 16 weeks, appetite at 28 weeks) were associated with maternal feeding practices of firstborns (structure and control-based feeding) at 1, 2, and 3 years, adjusting for firstborn child characteristics. A purposive subsample (n = 30) of mothers participated in semi-structured interviews to contextualize potential sibling influences on maternal feeding practices during infancy and toddlerhood. Quantitative data showed secondborn temperament and appetite were associated with how mothers fed their firstborn. Qualitative data explained maternal feeding practices in three primary ways: 1) Mothers explained shifting predictable meal and snack routines after birth of the secondborn, but did not perceive sibling characteristics as the source; 2) Family chaos following the secondborn's birth led to "survival mode" in feeding; and 3) Social support was protective against feeding resource dilution. The family systems process of resource dilution is a focus for future research and support for families during key transitions and a direction for efforts to reduce risk for child obesity.

Efficacy of the Fast Track Friendship Group Program for Peer-rejected Children: A Randomized-Controlled Trial.

OBJECTIVE: To evaluate the benefits of the Fast Track Friendship Group program implemented as a stand-alone school-based intervention on the social cognitions, social behavior, peer and teacher relationships of peer-rejected students. METHOD: Over four successive years, 224 peer-rejected elementary students (57% White, 17% Black, 20% Latinx, 5% multiracial; 68% male; grades 1-4; Mage = 8.1 years old) were identified using peer sociometric nominations and randomly assigned to the intervention (n = 110) or a treatment-as-usual control group (n = 114). Four school districts serving economically-disadvantaged urban and rural communities participated. Intervention involved weekly small group social skills training with classmate partners, with sessions tailored to address individual child needs. Consultation meetings held at the start and mid-point of intervention were designed to help teachers and parents support the generalization of targeted skills. RESULTS: Multi-level linear models, with children nested within schools (controlling for demographics and baseline scores) documented improvements in social-cognitive skills (direct assessments of emotion recognition and competent social problem-solving), social behavior (teacher ratings of social skills and externalizing behavior), and interpersonal relationships (peer sociometric nominations of peer acceptance and friendships, teacher-rated student-teacher closeness). Significant effects were generally small (ds = .19-.36) but consistent across child sex, grade level, and behavioral characteristics. CONCLUSIONS: The intervention proved feasible for high-fidelity implementation in school settings and produced significant improvements in the social adjustment of peer-rejected children, validating the approach as a school-based Tier 2 intervention.

Patient-specific solution of the electrocorticography forward problem in deforming brain.

Invasive intracranial electroencephalography (iEEG), or electrocorticography (ECoG), measures electric potential directly on the surface of the brain and can be used to inform treatment planning for epilepsy surgery. Combined with numerical modeling it can further improve accuracy of epilepsy surgery planning. Accurate solution of the iEEG forward problem, which is a crucial prerequisite for solving the iEEG inverse problem in epilepsy seizure onset zone localization, requires accurate representation of the patient's brain geometry and tissue electrical conductivity after implantation of electrodes. However, implantation of subdural grid electrodes causes the brain to deform, which invalidates preoperatively acquired image data. Moreover, postoperative magnetic resonance imaging (MRI) is incompatible with implanted electrodes and computed tomography (CT) has insufficient range of soft tissue contrast, which precludes both MRI and CT from being used to obtain the deformed postoperative geometry. In this paper, we present a biomechanics-based image warping procedure using preoperative MRI for tissue classification and postoperative CT for locating implanted electrodes to perform non-rigid registration of the preoperative image data to the postoperative configuration. We solve the iEEG forward problem on the predicted postoperative geometry using the finite element method (FEM) which accounts for patient-specific inhomogeneity and anisotropy of tissue conductivity. Results for the simulation of a current source in the brain show large differences in electric potential predicted by the models based on the original images and the deformed images corresponding to the brain geometry deformed by placement of invasive electrodes. Computation of the lead field matrix (useful for solution of the iEEG inverse problem) also showed significant differences between the different models. The results suggest that rapid and accurate solution of the forward problem in a deformed brain for a given patient is achievable.

Artificial intelligence for the evaluation of peripheral artery disease using arterial Doppler waveforms to predict abnormal ankle-brachial index.

BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk for major adverse limb and cardiac events including mortality. Developing screening tools capable of accurate PAD identification is a necessary first step for strategies of adverse outcome prevention. This study aimed to determine whether machine analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with PAD. METHODS: Consecutive patients (4/8/2015 - 12/31/2020) undergoing rest and postexercise ankle-brachial index (ABI) testing were included. Patients were randomly allocated to training, validation, and testing subsets (70%/15%/15%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict normal (> 0.9) or PAD (⩽ 0.9) using rest and postexercise ABI. A separate dataset of 151 patients who underwent testing during a period after the model had been created and validated (1/1/2021 - 3/31/2021) was used for secondary validation. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate test performance. RESULTS: Among 11,748 total patients, 3432 patients met study criteria: 1941 with PAD (mean age 69 ± 12 years) and 1491 without PAD (64 ± 14 years). The predictive model with highest performance identified PAD with an AUC 0.94 (CI = 0.92-0.96), sensitivity 0.83, specificity 0.88, accuracy 0.85, and positive predictive value (PPV) 0.90. Results were similar for the validation dataset: AUC 0.94 (CI = 0.91-0.98), sensitivity 0.91, specificity 0.85, accuracy 0.89, and PPV 0.89 (postexercise ABI comparison). CONCLUSION: An artificial intelligence-enabled analysis of a resting Doppler arterial waveform permits identification of PAD at a clinically relevant performance level.

Popliteal cysts are not a risk factor for lower extremity deep vein thrombosis.

BACKGROUND: Popliteal cysts (PC) result from distension of the gastrocnemio-semimembranosous bursa. Published reports indicate coincident PC and deep vein thrombosis (DVT). Whether the presence of PC increase the risk of deep vein thrombosis (DVT) remains unclear. METHODS: Lower extremity venous Duplex ultrasound (DUS) reports were evaluated across the Mayo Clinic Enterprise (Rochester, Minnesota, Jacksonville, Florida, Scottsdale, Arizona, and the Mayo Clinic Health System) in patients ≥ 18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute lower extremity DVT and PC from these reports. To determine whether there is a link between PC and lower extremity DVT, the frequency of PC among cases (ultrasounds with acute DVT) were compared to controls (ultrasounds without acute DVT). RESULTS: A total of 357,703 lower extremities venous DUS were performed in 237,052 patients (mean age 63.3 ± 16.6, 54.4% were female) between 1992 and 2021. Acute DVT was identified in 32,572 (9.1%) DUS, and PC in 32,448 (9.1%). PC were seen in a lower frequency (8.0%) of ultrasounds with acute DVT than those without (9.2%) acute DVT (OR: 0.85, 95% CI: 0.82 to 0.89, p < 0.001). In a multivariate logistic regression model after adjusting for age, sex, and race, PCs were not positively associated with acute DVT (adjusted OR: 0.84, 95% CI: 0.81 to 0.88). CONCLUSIONS: PC are an incidental finding or an alternative diagnosis on lower extremity venous DUS, a finding that increases significantly with age. PC were not a risk factor in the development of lower extremity DVT.

Single versus multiple and incidental versus symptomatic subsegmental pulmonary embolism: clinical characteristics and outcome.

It remains unexplored if the clinical picture and outcome of subsegmental pulmonary embolism (SSPE) differ between single versus multiple, and incidental versus symptomatic embolism. Consecutive patients anticoagulated for SSPE at the Mayo Thrombophilia Clinic (03/01/2013-12/31/2020) were followed forward to assess venous thromboembolism (VTE) recurrence, mortality, major bleeding, and clinically relevant non-major bleeding (CRNMB); expressed as a rate per 100 person-years. Among 3878 VTE patients, 1541 had pulmonary embolism including 224 (14.6%) with SSPE either single (n = 139) or multiple (n = 85; 46 bilateral and 39 unilateral emboli); 134 had incidental and 90 symptomatic SSPE. Patients with single were less often symptomatic and less often had coexisting DVT than multiple SSPE. Patients with incidental had a two-fold higher frequency of cancer compared to symptomatic SSPE. During the study period, 1 patient with single and 2 with multiple SSPE had VTE recurrence (rate of 1.14 vs 3.63, p = 0.280). Single SSPE patients experienced 2 episodes of major bleeding (rate of 2.36) while the multiple SSPE group had no major bleeding. Seven patients in each group had CRNMB events (rate of 8.20 vs 13.58 for single and multiple SSPE, respectively, p = 0.282). Patients with single SSPE had a higher death rate compared to multiple SSPE (43.07 vs 22.22, p = 0.031) but no difference was noted after adjusting for cancer (p = 0.388). Also, incidental had similar clinical outcomes to symptomatic SSPE.Interpretation Anticoagulated SSPE patients with single and multiple as well as incidental and symptomatic have a different clinical profile but similar clinical outcomes.

Targeting the Proximal Mechanisms of Stress Adaptation in Early Adolescence to Prevent Mental Health Problems in Youth in Poverty.

OBJECTIVE: This study used a randomized clinical trial design to evaluate the success with which The Building a Strong Identity and Coping Skills intervention (BaSICS) engaged the proximal mechanisms of poverty-related stress's impact on the psychosocial functioning and mental health of young adolescents living in high poverty contexts. METHOD: 129 youth from very low-income families were randomized to receive the 32-hour group-based intervention or no-treatment control - 16 of these families withdrew before the intervention groups began. The remaining 113 youth aged 11-12 (53% assigned to intervention; 54% female; 40% Hispanic, 63% Black, 20% White) participated in the study, which included four assessment waves: pretest, posttest, 6-month follow-up and 12-month follow-up assessments. Primary control, secondary control, and disengagement coping were assessed via a combination of parent and youth reports as well as via interviews and questionnaires. Hypothalamic-pituitary-adrenal axis (HPA) reactivity was assessed via salivary cortisol responses occurring during a lab-based stress induction (Trier Social Stress Test). RESULTS: Multilevel regression models with repeated measures nested within subjects revealed that in comparison to controls, intervention youth had sustained significant increases in their knowledge about primary control coping (e.g., problem solving, emotion modulation), knowledge and utilization of secondary control (e.g., cognitive restructuring) coping, as well as decreased reliance on disengagement coping. These were accompanied by decreased cortisol reactivity in intervention versus control youth. CONCLUSIONS: These findings support that BaSICS engages several proximal mechanisms of poverty-related stress' impact on early adolescent mental health - coping skills and HPA reactivity - during the neurodevelopmentally plastic pubertal period.

Building long-term family resilience through universal prevention: 10-year parent and child outcomes during the COVID-19 pandemic.

As the COVID-19 pandemic has been highly stressful for parents and children, it is clear that strategies that promote long-term family resilience are needed to protect families in future crises. One such strategy, the Family Foundations program, is focused on promoting supportive coparenting at the transition to parenthood. In a randomized trial, we tested the long-term intervention effects of Family Foundations on parent, child, and family well-being one to two months after the imposition of a national shelter-in-place public health intervention in 2020. We used regression models to test intervention impact on outcomes reported on by parents in a standard questionnaire format and a series of 8 days of daily reports. We also tested moderation of intervention impact by parent depression and coparenting relationship quality. Relative to control families, intervention families demonstrated significantly lower levels of individual and family problems (general parent hostility, harsh and aggressive parenting, coparenting conflict, sibling relationship conflict, and children's negative mood and behavior problems), and higher levels of positive family relationship quality (positive parenting, couple relationship quality, sibling relations, and family cohesion). For some outcomes, including coparenting conflict, harsh parenting, and child behavior problems, intervention effects were larger for more vulnerable families-that is, families with higher pre-pandemic levels of parent depression or lower levels of coparenting relationship quality. We conclude that targeted family prevention programming is able to promote healthy parent and child functioning during unforeseen future periods of acute stress. The long-term benefits of a universal approach to family support at the transition to parenthood indicate the need for greater investment in the dissemination of effective approaches.

Dado que la pandemia de COVID-19 ha sido muy estresante para padres e hijos, está claro que se necesitan estrategias que promuevan la resiliencia familiar a largo plazo para proteger a las familias en crisis futuras. Una de esas estrategias, el programa Family Foundations, se centra en promover la crianza compartida de apoyo en la transición a la paternidad. En un ensayo aleatorizado, probamos los efectos de la intervención a largo plazo de Family Foundations en el bienestar de los padres, el niño y la familia uno o dos meses después de la imposición de una intervención nacional de salud pública de refugio en el lugar en 2020. Usamos modelos de regresión para evaluar el impacto de la intervención en los resultados informados por los padres en un formato de cuestionario estándar y una serie de 8 días de informes diarios. También probamos la moderación del impacto de la intervención por la depresión de los padres y la calidad de la relación de coparentalidad. En relación con las familias de control, las familias de intervención demostraron niveles significativamente más bajos de problemas individuales y familiares (hostilidad general de los padres, crianza dura y agresiva, conflicto de crianza conjunta, conflicto de relaciones entre hermanos y problemas de comportamiento y estado de ánimo negativos de los niños) y niveles más altos de calidad de relación familiar positiva (crianza positiva, calidad de la relación de pareja, relaciones entre hermanos y cohesión familiar). Para algunos resultados, incluido el conflicto de crianza compartida, la crianza severa y los problemas de comportamiento infantil, los efectos de la intervención fueron mayores para las familias más vulnerables, es decir, familias con niveles más altos de depresión de los padres prepandémicos o niveles más bajos de calidad de la relación de crianza compartida. Concluimos que los programas de prevención familiar específicos pueden promover el funcionamiento saludable de padres e hijos durante períodos futuros imprevistos de estrés agudo. Los beneficios a largo plazo de un enfoque universal del apoyo familiar en la transición a la paternidad indican la necesidad de una mayor inversión en la difusión de enfoques eficaces.

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

OBJECTIVES: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg. METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. RESULTS: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01). CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Hemoglobin levels and coronary heart disease risk by age, race, and sex in the reasons for geographic and racial differences in stroke study (REGARDS).

Higher and lower hemoglobin concentrations are associated with coronary heart disease (CHD), but whether this risk is consistent across age, sex, and race is unclear. The Reasons for Geographic And Racial Differences in Stroke (REGARDS) study is an observational cohort study of 30 239 black, and white, adults aged 45 and older recruited 2003-7. Participants were included if they had hemoglobin measures, were CHD-free at baseline, and had all baseline variables. The primary outcome was incident CHD. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident CHD by hemoglobin concentration. This was expressed as a continuous variable and divided into age-, sex-, and race-specific quintiles. The 16 332 participants were included, contributing 114 362 person-years of follow-up and 915 incident CHD events. The mean age was 63 years, 35% were male, 41% were black, and the mean baseline hemoglobin was 13.6 g/dL (SD 1.4). A significant non-linear association between hemoglobin and CHD was identified (P < .001). This association differed significantly by race (P = .025) but not by sex or age. In whites, the risk for incident CHD was higher in the lowest (HR 2.28, 95% CI 1.61, 3.33) and highest (HR 1.94, 95% CI 1.35, 2.79) hemoglobin quintiles relative to the third quintile. For blacks, only those in the lowest hemoglobin quintile had an increased risk for incident CHD events (HR 1.70, 95% CI 1.20, 2.41). Hemoglobin is an independent risk factor for CHD in whites and blacks but with different hemoglobin concentrations conferring different risks.

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban.

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.