Impact of prenatal maternal depression on gestational length: post hoc analysis of a randomized clinical trial.

Background: Shortened gestation is a leading cause of childhood morbidity and mortality with lifelong consequences for health. There is a need for public health initiatives on increasing gestational age at birth. Prenatal maternal depression is a pervasive health problem robustly linked via correlational and epidemiological studies to shortened gestational length. This proof-of-concept study tests the impact of reducing prenatal maternal depression on gestational length with analysis of a randomized clinical trial (RCT). Methods: Participants included 226 pregnant individuals enrolled into an RCT and assigned to receive either interpersonal psychotherapy (IPT) or enhanced usual care (EUC). Recruitment began in July 2017 and participants were enrolled August 10, 2017 to September, 8 2021. Depression diagnosis (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; DSM 5) and symptoms (Edinburgh Postnatal Depression Scale and Symptom Checklist) were evaluated at baseline and longitudinally throughout gestation to characterize depression trajectories. Gestational dating was collected based on current guidelines via medical records. The primary outcome was gestational age at birth measured dichotomously (≥39 gestational weeks) and the secondary outcome was gestational age at birth measured continuously. Posthoc analyses were performed to test the effect of reducing prenatal maternal depression on gestational length. This trial is registered with ClinicalTrials.gov (NCT03011801). Findings: Steeper decreases in depression trajectories across gestation predicted later gestational age at birth, specifically an increase in the number of full-term babies born ≥39 gestational weeks (EPDS linear slopes: OR = 1.54, 95% CI 1.10-2.16; and SCL-20 linear slopes: OR = 1.67, 95% CI 1.16-2.42). Causal mediation analyses supported the hypothesis that participants assigned to IPT experienced greater reductions in depression symptom trajectories, which in turn, contributed to longer gestation. Supporting mediation, the natural indirect effect (NIE) showed that reduced depression trajectories resulting from intervention were associated with birth ≥39 gestational weeks (EPDS, OR = 1.65, 95% CI 1.02-2.66; SCL-20, OR = 1.85, 95% CI 1.16-2.97). Interpretation: We used a RCT design and found that reducing maternal depression across pregnancy was associated with lengthened gestation. Funding: This research was supported by the NIH (R01 HL155744, R01 MH109662, R21 MH124026, P50 MH096889).

Higher prenatal anxiety predicts lower neonatal hair cortisol.

BACKGROUND: Prenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. METHOD: Pregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75-2.00). RESULTS: Both higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: ß = -0.614, p =.012; slope: ß = -0.681, p =.006), but not general anxiety (intercept: ß = -0.389, p =.114; slope: ß = -0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. CONCLUSION: Cortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Obesity in heart failure with preserved ejection fraction: Insights from the REDUCE LAP-HF II trial.

AIMS: Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. METHODS AND RESULTS: The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2 . As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e' were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. CONCLUSIONS: Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

Association of a Heart Failure Management Incentive in Primary Care With Clinical Outcomes: A Retrospective Cohort Study.

BACKGROUND: We aim to examine the association between primary care physicians' billing of Q050A, a pay-for-performance heart failure (HF) management incentive fee code, and the composite outcome of mortality, hospitalization, and emergency department visits. METHODS AND RESULTS: This population-based cohort study linked administrative health databases in Ontario, Canada, for patients with HF aged >66 years between January 1, 2008, and March 31, 2020. Cases were patients with HF who had a Q050A fee code billed. Cases and controls were matched 1:1 on age, sex, patient status on being rostered to a primary care physician, cardiologist, or internist visit in the 6 months before study enrollment, Johns Hopkins Adjusted Clinical Group resource use bands, days between HF diagnosis and study enrollment (±2 years), and the logit of the propensity score. A Cox proportional hazards model assessed the association of Q050A with the outcome. A total of 59 664 cases had a Q050A billed, whereas 244 883 patients did not. Before matching, patients who had a Q050A billed were more likely to be men (52% versus 49%), were rostered to a primary care physician (100% versus 96%), had a higher Charlson Comorbidity Index, and had higher health care costs. The mean follow-up was 481 days for cases and 530 days for controls. The composite outcome (hazard ratio, 1.11 [95% CI, 1.09-1.12]) was significantly higher for cases than controls. CONCLUSIONS: The Q050A incentive improved financial compensation for primary care physicians managing patients with HF but was not associated with improvements in the outcome. Research on promoting evidence-based HF management is warranted.

Epidemiology and treatment of heart failure with chronic obstructive pulmonary disease in Canadian primary care.

AIMS: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are largely managed in primary care, but their intersection in terms of disease burden, healthcare utilization, and treatment is ill-defined. METHODS AND RESULTS: We examined a retrospective cohort including all patients with HF or COPD in the Canadian Primary Care Sentinel Surveillance Network from 2010 to 2018. The population size in 2018 with HF, COPD, and HF with COPD was 15 778, 27 927, and 4768 patients, respectively. While disease incidence declined, age-sex-standardized prevalence per 100 population increased for HF alone from 2.33 to 3.63, COPD alone from 3.44 to 5.96, and COPD with HF from 12.70 to 15.67. Annual visit rates were high and stable around 8 for COPD alone but declined significantly over time for HF alone (9.3-8.1, P = 0.04) or for patients with both conditions (14.3-11.9, P = 0.006). For HF alone, cardiovascular visits were common (29.4%), while respiratory visits were infrequent (3.5%), with the majority of visits being non-cardiorespiratory. For COPD alone, respiratory and cardiovascular visits were common (16.4% and 11.3%) and the majority were again non-cardiorespiratory. For concurrent disease, 39.0% of visits were cardiorespiratory. The commonest non-cardiorespiratory visit reasons were non-specific symptoms or signs, endocrine, musculoskeletal, and mental health. In patients with HF with and without COPD, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor use was similar, while mineralocorticoid receptor antagonist use was marginally higher with concurrent COPD. Beta-blocker use was initially lower with concurrent COPD compared with HF alone (69.3% vs. 74.0%), but this progressively declined by 2018 (74.5% vs. 73.5%). CONCLUSIONS: The prevalence of HF and COPD continues to rise. Although patients with either or both conditions are high utilizers of primary care, the majority of visits relate to non-cardiorespiratory comorbidities. Medical therapy for HF was similar and the initially lower beta-blocker utilization disappeared over time.

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

BACKGROUND: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. METHODS: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. RESULTS: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. CONCLUSIONS: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04009798.

Effect of Brief Interpersonal Therapy on Depression During Pregnancy: A Randomized Clinical Trial.

Importance: Prenatal depression is prevalent with negative consequences for both the mother and developing fetus. Brief, effective, and safe interventions to reduce depression during pregnancy are needed. Objective: To evaluate depression improvement (symptoms and diagnosis) among pregnant individuals from diverse backgrounds randomized to brief interpersonal psychotherapy (IPT) vs enhanced usual care (EUC). Design, Setting, and Participants: A prospective, evaluator-blinded, randomized clinical trial, the Care Project, was conducted among adult pregnant individuals who reported elevated symptoms during routine obstetric care depression screening in general practice in obstetrics and gynecology (OB/GYN) clinics. Participants were recruited between July 2017 and August 2021. Repeated measures follow-up occurred across pregnancy from baseline (mean [SD], 16.7 [4.2] gestational weeks) through term. Pregnant participants were randomized to IPT or EUC and included in intent-to-treat analyses. Interventions: Treatment comprised an engagement session and 8 active sessions of brief IPT (MOMCare) during pregnancy. EUC included engagement and maternity support services. Main Outcomes and Measures: Two depression symptom scales, the 20-item Symptom Checklist and the Edinburgh Postnatal Depression Scale, were assessed at baseline and repeatedly across pregnancy. Structured Clinical Interview for DSM-5 ascertained major depressive disorder (MDD) at baseline and the end of gestation. Results: Of 234 participants, 115 were allocated to IPT (mean [SD] age, 29.7 [5.9] years; 57 [49.6%] enrolled in Medicaid; 42 [36.5%] had current MDD; 106 [92.2%] received intervention) and 119 to EUC (mean [SD] age, 30.1 [5.9] years; 62 [52.1%] enrolled in Medicaid; 44 [37%] had MDD). The 20-item Symptom Checklist scores improved from baseline over gestation for IPT but not EUC (d = 0.57; 95% CI, 0.22-0.91; mean [SD] change for IPT vs EUC: 26.7 [1.14] to 13.6 [1.40] vs 27.1 [1.12] to 23.5 [1.34]). IPT participants more rapidly improved on Edinburgh Postnatal Depression Scale compared with EUC (d = 0.40; 95% CI, 0.06-0.74; mean [SD] change for IPT vs EUC: 11.4 [0.38] to 5.4 [0.57] vs 11.5 [0.37] to 7.6 [0.55]). MDD rate by end of gestation had decreased significantly for IPT participants (7 [6.1%]) vs EUC (31 [26.1%]) (odds ratio, 4.99; 95% CI, 2.08-11.97). Conclusions and Relevance: In this study, brief IPT significantly reduced prenatal depression symptoms and MDD compared with EUC among pregnant individuals from diverse racial, ethnic, and socioeconomic backgrounds recruited from primary OB/GYN clinics. As a safe, effective intervention to relieve depression during pregnancy, brief IPT may positively affect mothers' mental health and the developing fetus. Trial Registration: ClinicalTrials.gov Identifier: NCT03011801.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).

Cardiovascular outcomes in children with Kawasaki disease: a population-based cohort study.

BACKGROUND: The risk of cardiovascular events after Kawasaki disease (KD) remains uncertain. Our objective was to determine the risk of cardiovascular events and mortality after KD. METHODS: Population-based retrospective cohort study using Ontario health administrative databases (0-18 years; 1995-2018). EXPOSURE: pediatric KD hospitalizations. Each case was matched to 100 non-exposed controls. PRIMARY OUTCOME: major adverse cardiac events (MACE; cardiovascular death, myocardial infarction, or stroke composite). SECONDARY OUTCOMES: composite cardiovascular events and mortality. We determined incidence rates and adjusted hazard ratios (aHR) using multivariable Cox models. RESULTS: Among 4597 KD survivors, 79 (1.7%) experienced MACE, 632 (13.8%) composite cardiovascular events, and 9 (0.2%) died during 11-year median follow-up. The most frequent cardiovascular events among KD survivors were ischemic heart disease (4.6 events/1000 person-years) and arrhythmias (4.5/1000 person-years). KD survivors were at increased risk of MACE between 0-1 and 5-10 years, and composite cardiovascular events at all time periods post-discharge. KD survivors had a lower mortality risk throughout follow-up (aHR 0.36, 95% CI 0.19-0.70). CONCLUSION: KD survivors are at increased risk of post-discharge cardiovascular events but have a lower risk of death, which justifies enhanced cardiovascular disease surveillance in these patients. IMPACT: Among 4597 Kawasaki disease (KD) survivors, 79 (1.7%) experienced major adverse cardiac events (MACE) and 632 (13.8%) had composite cardiovascular events during 11-year median follow-up. KD survivors had significantly higher risks of post-discharge MACE and cardiovascular events versus non-exposed children. Only nine KD survivors (0.2%) died during follow-up, and the risk of mortality was significantly lower among KD survivors versus non-exposed children. Childhood KD survivors should receive preventative counseling and cardiovascular surveillance, aiming to mitigate adult cardiovascular disease.

Maternal adverse childhood experiences and infant subcortical brain volume.

Background: A large body of research supports the deleterious effects of adverse childhood experiences (ACEs) on disease susceptibility and health for both the exposed individual and the next generation. It is likely that there is an intergenerational transmission of risk from mother to child; however, the mechanisms through which such risk is conferred remain unknown. The current study evaluated the association between maternal ACEs, neonatal brain development of the amygdala and hippocampus, and later infant negative emotionality at six months of age. Methods: The sample included 85 mother-infant dyads (44 female infants) from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Experiences Questionnaire (ACE-Q) and neonatal hippocampal and amygdala volume was assessed using structural magnetic resonance imaging (MRI). Infant negative emotionality was assessed at 6 months using the Infant Behavior Questionnaire (IBQ). Results: Multivariate analyses demonstrated that maternal ACEs were associated with bilateral amygdala volume (F(2,78) = 3.697,p = .029). Specifically, higher maternal ACEs were associated with smaller left (ß = -0.220, t(79) = -2.661, p = .009, R2 = 0.494, and right (ß = -0.167, t(79) = -2.043, p = .044, R2 = 0.501) amygdala volume. No significant association between maternal ACEs and bilateral hippocampal volume (F(2,78) = 0.215,p = .0807) was found. Follow-up regression analyses demonstrated that both high maternal ACEs and smaller left amygdala volume were associated with higher infant negative emotionality at six months of age (ß = .232, p = .040, R2 = 0.094, and ß = -0.337, p = .022, R2 = 0.16, respectively) although statistically significant mediation of this effect was not observed (Indirect effect = 0.0187, 95% CI [-0.0016-0.0557]). Conclusions: Maternal ACEs are associated with both newborn amygdala volume and subsequent infant negative emotionality. These findings linking maternal adverse childhood experiences and infant brain development and temperament provide evidence to support the intergenerational transmission of adversity from mother to child.

Longitudinal and prospective assessment of prenatal maternal sleep quality and associations with newborn hippocampal and amygdala volume.

BACKGROUND: The rapid maturation of the fetal brain renders the fetus susceptible to prenatal environmental signals. Prenatal maternal sleep quality is known to have important health implications for newborns including risk for preterm birth, however, the effect on the fetal brain is poorly understood. METHOD: Participants included 94 pregnant participants and their newborns (53% female). Pregnant participants (Mage = 30; SDage= 5.29) reported on sleep quality three times throughout pregnancy. Newborn hippocampal and amygdala volumes were assessed using structural magnetic resonance imaging. Multilevel modeling was used to test the associations between trajectories of prenatal maternal sleep quality and newborn hippocampal and amygdala volume. RESULTS: The overall trajectory of prenatal maternal sleep quality was associated with hippocampal volume (left: b = 0.00003, p = 0.013; right: b = 0.00003, p = .008). Follow up analyses assessing timing of exposure indicate that poor sleep quality early in pregnancy was associated with larger hippocampal volume bilaterally (e.g., late gestation left: b = 0.002, p = 0.24; right: b = 0.004, p = .11). Prenatal sleep quality was not associated with amygdala volume. CONCLUSION: These findings highlight the implications of poor prenatal maternal sleep quality and its role in contributing to newborn hippocampal development.

Needs, Barriers and Facilitators of Adolescents Participating in a Lifestyle Promotion Program in Oncology: Stakeholders, Adolescents and Parents' Perspective.

Treatments for adolescent cancer can cause debilitating side effects in the short- and long-term such as nausea and malnutrition but also cardiometabolic disturbances. Although the risk for cardiometabolic complications is greater for adolescents with cancer than younger ones, adolescents typically respond poorly to family-oriented health promotion programs. This study aims to assess the needs, barriers and facilitators to healthy lifestyle promotion interventions for adolescents with cancer and how to best adapt these interventions for them. Interviews were held with adolescents treated for cancer (n = 9) and parents (n = 6), focus groups were conducted with stakeholders working in oncology (n = 12) and self-report questionnaires were sent to stakeholders involved in a health promotion intervention (n = 6). At the time of interview, mean age of adolescent participants (40% female) was 17.0 ± 1.9 years (mean age at diagnosis: 14.6 ± 1.6 years). Verbatim and responses to questionnaires were coded and analyzed using qualitative methods. Stakeholder stated that adolescents with cancer need to access activities adapted to their age, to communicate with peers going through a similar experience, and to preserve their schooling and friendships. Barriers to intervention reported by adolescents, parents and stakeholders include lack of motivation, schedule conflicts, fatigue and treatment side effects. Some of the barriers mentioned by adolescents and parents include pain, post-surgery problems, school, physical deconditioning, and lack of time. Facilitators mentioned by adolescents and parents comprise trust in stakeholders' expertise, personalized approaches, scheduling flexibility. Stakeholders recommended to build trust in the relationship, favoring non-moralizing teachings, adapt interventions to adolescents' limited attention span and avoiding the use of long-term health benefits as a motivator.

The State of Heart Failure Care in Canada: Minimal Improvement in Readmissions Over Time Despite an Increased Number of Evidence-Based Therapies.

Background: An unanswered question is whether the combination of advances in medical and device therapy over the past decade has translated into improved outcomes for patients with heart failure (HF) in Canada. Methods: The Canadian Institute for Health Information (CIHI) Hospital Morbidity Database was used to identify hospitalizations for HF among patients aged 18 years and older in Canadian hospitals during fiscal years 2009/2010 and 2018/2019. We assessed interprovincial differences in age, sex, length of stay (LOS), discharge disposition, type of admitting hospital, and most responsible service, for all HF admissions. National and provincial rates of HF admissions and all-cause 30-day readmissions were calculated. Results: After adjusting for age, the rate of HF admissions in Canada was 216 per 100,000 population in 2009/2010 and 2018/2019. The majority of patients with HF were admitted to general internal medicine and community hospitals in both 2009/2010 and 2018/2019. The national, crude, all-cause 30-day readmission rate stayed constant at 20.6%, and the majority of patients were readmitted with the diagnosis of HF in both 2009/2010 (62.5%) and 2018/2019 (59.0%). Median and interquartile range of HF LOS also remained unchanged at 7 days (3-14). Conclusions: The national rate of HF admissions, 30-day readmissions, and HF LOS have remained unchanged from 2009/2010 to 2018/2019, despite advances in medical and device therapy during this timeframe.

Introduction: La question demeure de savoir si, au cours de la dernière décennie au Canada, la combinaison des avancées dans les traitements médicaux et à l'aide d'un dispositif s'est traduite par de meilleurs résultats cliniques chez les patients atteints d'insuffisance cardiaque (IC). Méthodes: Nous avons utilisé la base de données sur la morbidité hospitalière de l'Institut canadien d'information sur la santé (ICIS) pour recenser les hospitalisations de patients atteints d'IC âgés de 18 ans et plus dans les hôpitaux du Canada au cours des années financières 2009/2010 et 2018/2019. Nous avons évalué les différences interprovinciales selon l'âge, le sexe, la durée du séjour (DDS), l'état à la sortie, le type d'hôpital à l'admission et le service le plus tenu à la prise en charge du patient, de toutes les admissions liées à l'IC. Nous avons calculé les taux provinciaux et national des admissions liées à l'IC et les réadmissions toutes causes confondues dans les 30 jours. Résultats: Après ajustement en fonction de l'âge, le taux d'admissions liées à l'IC au Canada était de 216 pour 100 000 habitants en 2009/2010 et en 2018/2019. La majorité des patients atteints d'IC avaient été admis en médecine interne générale et dans les hôpitaux communautaires en 2009/2010 et en 2018/2019. Le taux national, brut, toutes causes confondues de réadmissions dans les 30 jours était resté constant à 20,6 %, et la majorité des patients avaient eu des réadmissions liées au diagnostic d'IC en 2009/2010 (62,5 %) et en 2018/2019 (59,0 %). L'écart interquartile et la médiane de la DDS liée à l'IC étaient aussi demeurés inchangés après 7 jours (3-14). Conclusions: Le taux national des admissions liées à l'IC, les réadmissions dans les 30 jours et la DDS liée à l'IC étaient demeurés inchangés de 2009/2010 à 2018/2019, malgré les avancées des traitements médicaux et à l'aide d'un dispositif durant cette période de temps.

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF).

Background: Thiamine supplementation may improve cardiac function in older adults with heart failure (HF). Our objectives were to determine the following: (i) the feasibility of conducting a large trial of thiamine supplementation in HF; and (ii) the effects of thiamine on clinical outcomes. Methods: We conducted a double-blinded randomized placebo-controlled 2-period crossover feasibility study from June 2018 to April 2021. Adults aged ≥ 60 years with symptomatic HF and reduced ejection fraction (≤ 45%) were included. Participants were randomized to thiamine mononitrate 500 mg, or placebo, for 90 days and were switched to the opposite treatment for 90 days after a 6-week washout period. The primary feasibility outcome was recruitment of 24 participants in 11 months. Results: We screened 330 patients over 21 months to recruit 24 patients. Participants' mean age was 73.4 years. The targets for refusal rate, retention rate, and adherence rate were met. Nonsignificant improvements occurred in left ventricular ejection fraction and N-terminal pro-brain natriuretic peptide (NT-proBNP) level with thiamine. A total of 13 serious adverse events occurred in 7 patients; none were related to the study drug. Conclusions: Although we did not reach our recruitment target, we found high-dose thiamine supplementation to be well tolerated, with potential improvements in biomarker outcomes. A larger trial of thiamine supplementation is warranted.

Introduction: La supplémentation en thiamine peut améliorer la fonction cardiaque chez les personnes âgées atteintes d'insuffisance cardiaque (IC). Nos objectifs visaient à déterminer : (i) la faisabilité d'un essai de grande envergure sur la supplémentation en thiamine lors d'IC ; (ii) les effets de la thiamine sur les résultats cliniques. Méthodes: Nous avons réalisé une étude de faisabilité croisée à double insu et à répartition aléatoire contre placebo sur deux périodes de juin 2018 à avril 2021. Nous avons retenu les adultes de ≥ 60 ans qui avaient une IC symptomatique et une fraction d'éjection réduite (≤ 45 %). Nous avons réparti les participants de façon aléatoire pour recevoir 500 mg de mononitrate de thiamine ou le placebo durant 90 jours, et avons inversé le traitement durant 90 jours après une période de lavage de 6 semaines. Le principal critère de faisabilité était le recrutement de 24 participants en 11 mois. Résultats: Nous avons recruté 24 patients sur les 330 patients sélectionnés durant 21 mois. L'âge moyen des participants était de 73,4 ans. Les cibles des taux de refus, des taux de rétention et des taux d'adhésion ont été atteintes. Avec la thiamine, nous avons observé des améliorations non significatives de la fraction d'éjection ventriculaire gauche et de la concentration de propeptide natriurétique de type B N-terminal (NT-proBNP). Parmi les 13 événements indésirables sérieux qu'ont subis sept patients, aucun n'a été associé au médicament étudié. Conclusions: Bien que nous n'ayons pas atteint notre cible de recrutement, nous avons observé que la supplémentation en thiamine à dose élevée était bien tolérée et qu'il y avait des améliorations potentielles des résultats des biomarqueurs. Un essai de plus grande envergure sur la supplémentation en thiamine est justifié.

Prenatal exposure to maternal psychological distress and telomere length in childhood.

Telomere length (TL) is a biological marker of cellular aging, and shorter TL in adulthood is associated with increased morbidity and mortality risk. It is likely that these differences in TL are established long before adulthood, and there is growing evidence that TL can reflect prenatal experiences. Although maternal prenatal distress predicts newborn TL, it is unknown whether the relation between prenatal exposure to maternal distress and child TL persists through childhood. The purpose of the current longitudinal, prospective study is to examine the relation between prenatal exposure to maternal distress (perceived stress, depressive symptoms, pregnancy-related anxiety) and TL in childhood. Participants included 102 children (54 girls) and their mothers. Mothers' distress was assessed five times during pregnancy, at 12 weeks postpartum, and at the time of child telomere measurement between 6 and 16 years of age. Maternal distress during pregnancy predicted shorter offspring TL in childhood, even after accounting for postnatal exposure to maternal distress and other covariates. These findings indicate that maternal mental health predicts offspring TL biology later in childhood than previously observed. This study bolsters claims that telomere biology is subject to fetal programming and highlights the importance of supporting maternal mental health during pregnancy.

The predictive utility of functional status at discharge: a population-level cohort analysis.

BACKGROUND: Functional status is a patient-important, patient-centered measurement. The utility of functional status measures to inform post-discharge patient needs is unknown. We sought to examine the utility of routinely collected functional status measures gathered from older hospitalized patients to predict a panel of post-discharge outcomes. METHODS: In this population-based retrospective cohort study, Adults 65+ discharged from an acute hospitalization between 4 November 2008 and 18 March 2016 in Ontario, Canada and received an assessment of functional status at discharge using the Health Outcomes for Better Information and Care tool were included. Multivariable regression analysis was used to determine the relationship between functional status and emergency department (ED) re-presentation, hospital readmission, long term care facility (LTCF) admission or wait listing ('LTCF readiness'), and death at 180 days from discharge. RESULTS: A total of 80 020 discharges were included. 38 928 (48.6%) re-presented to the ED, 24 222 (30.3%) were re-admitted, 5 037 (6.3%) were LTCF ready, and 9 047 (11.3%) died at 180 days. Beyond age, diminished functional status at discharge was the factor most associated with LTCF readiness (adjusted Odds Ratio [OR] 4.11 for those who are completely dependent for activities of daily living compared to those who are independent; 95% Confidence Interval [CI]: 3.70-4.57) and death (OR 3.99; 95% CI: 3.67-4.35). Functional status also had a graded relationship with each outcome and improved the discriminability of the models predicting death and LTCF readiness (p<0.01) but not ED re-presentation or hospital re-admission. CONCLUSION: Routinely collected functional status at discharge meaningfully improves the prediction of long term care home readiness and death. The routine assessment of functional status can inform post-discharge care and planning for older adults.

Experiences of Discrimination and Depression Trajectories over Pregnancy.

INTRODUCTION: Research on risk factors for prenatal depression is critical to improve the understanding, prevention, and treatment of women's psychopathology. The current study examines the relation between experiences of racial discrimination and trajectories of depression symptoms over the course of pregnancy. METHOD: Participants completed standardized measures regarding symptoms of depression at four timepoints during pregnancy and reported on experiences of racial discrimination at one timepoint. Latent growth curve modeling was used to examine the relation between discrimination and initial levels (intercept) and trajectories (slope) of depression symptoms over pregnancy. RESULTS: Participants were 129 pregnant individuals recruited from obstetric clinics and oversampled for elevated depression symptoms. Thirty-six percent of the participants were living at or below 200% of the federal poverty line. Fifty-four percent of the sample identified as non-Latinx White, 26% as Latinx, and 13% as non-Latinx Black. An unconditional latent growth curve modeling revealed a negative quadratic trajectory of depression symptoms during pregnancy. When women's report of discrimination was added as a predictor of depression trajectories, discrimination predicted the initial value (intercept) of depression symptoms, but not change over the course of pregnancy (slope). Specifically, higher levels of experiences of discrimination were associated with higher levels of depression symptoms. When sociodemographic and contextual covariates were included in the model, a low family income-to-needs ratio was also related to higher levels of depression symptoms. CONCLUSIONS: These findings provide evidence that women's experiences of racial discrimination and family financial strain are risk factors for prenatal depression, with implications for screening, treatment, and policy.