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Objective: The goal of this study is to determine the strength of association between treatment with triptans and acute myocardial infarction, heart failure, and death. Background: Case reports in the literature have raised concerns over an association between treatment of migraine headaches with triptans and cardiovascular events. This study aims to systematically evaluate this association in a contemporary population‐based cohort. We hypothesized that triptan exposure is not associated with increased cardiovascular events. Methods: A retrospective cohort study was conducted within an integrated healthcare delivery system in Southern California. From January 2009 to December 2018, 189,684 patients age ≥18 years had a diagnosis of migraine. In this group, 130,656 were exposed to triptans. Patients treated with triptans were matched 1:1 to those not exposed to triptans by using a propensity score. The primary outcome was acute myocardial infarction; secondary outcomes were heart failure, all‐cause death, and combined acute myocardial infarction, heart failure, and death. Results: The incidence rate of acute myocardial infarction was 0.67 per 1000 person‐year in triptan‐exposed vs 1.44 per 1000 person‐year in not exposed patients. In propensity‐matched analyses, the adjusted hazard ratio for triptan exposure was 0.95 (95% confidence interval [CI] 0.84‐1.08) for acute myocardial infarction; 1.00 (95% CI 0.93‐1.08) for all‐cause death; 0.93 (95% CI 0.81‐1.08) for heart failure; and 0.99 (95% CI 0.93‐1.06) for a composite of acute myocardial infarction, heart failure, or death. Sensitivity analyses focusing on stratified subgroups based on age, gender, ethnicity, and several cardiac risk factors also revealed no significant association between triptan exposure and cardiovascular events. Conclusions: No association was found between exposure to triptans and an increased risk of cardiovascular events. These data provide reassurance regarding the cardiovascular safety of utilizing triptans for the medical management of migraine headaches. [ABSTRACT FROM AUTHOR]

Heart failure is an uncommon diagnosis among pregnant women with limited data on this condition. We sought to describe the characteristics and outcomes of pregnant women with heart failure stratified by etiologies of cardiomyopathy. This is a retrospective population-based cohort study across medical centers in Southern California in the United States. Pregnant women with heart failure were identified using ICD-9 codes and adjudicated by manual review of the medical records. Obstetric complications, fetal birthweight, and maternal mortality outcomes were evaluated. Between 2003 and 2014, there were 488 pregnancies (0.1% of all pregnancies) complicated by heart failure, of which 333 (68.2%) were due to peripartum cardiomyopathy (PPCM) and 155 (31.8%) were due to other etiologies (non-PPCM). Compared to patients with non-PPCM, patients with PPCM were more likely to be Black Americans (26.7% vs 15.5%) or Asian Americans (16.8% vs 7.1%). A high proportion of PPCM patients had preeclampsia (11.1% vs 5.2%, p = 0.04). Infants born to mothers with non-PPCM were more likely to be small for gestational age (SGA) (SGA <3% 4.1% vs 9.7%, p < 0.001; SGA <10% 20% vs 8.8%, p = 0.001). No significant difference in maternal mortality was observed between PPCM and non-PPCM patients. PPCM is the most common etiology of HF during pregnancy. Infants born to mothers with PPCM were likely to be small for gestational age. • Peripartum cardiomyopathy comprised of 68% of heart failure cases in pregnant women. • Pre-eclampsia was more common in patients with peripartum cardiomyopathy • A higher proportion of infants born to mothers with non-peripartum cardiomyopathy were small for gestational age. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: The goal of this study was to describe the pattern of statin adherence in older patients, aged 80 years or older; identify factors associated with high adherence; and determine the association between statin adherence and all‐cause mortality. DESIGN: Retrospective population‐based cohort study. SETTING: An integrated healthcare system in Southern California. PARTICIPANTS: Patients hospitalized with a principal diagnosis of acute myocardial infarction (MI) between January 1, 2006, and December 31, 2016. MEASUREMENTS: Statin adherence, as measured using pharmacy dispensing records over the 365 days following hospital discharge, based on proportion of days covered (PDC). Adherence levels were categorized as high (PDC 80% or higher), partial (PDC 40% or higher and lower than 80%), and low (PDC lower than 40%). RESULTS: Between 2006 and 2016, 5629 patients, 80 years or older, hospitalized for acute MI met the inclusion criteria. Among this group, 68.8% were highly adherent to statin therapy, 20.4% were partially adherent, and 10.8% were not adherent. Male sex (odds ratio [OR] = 1.42; 95% confidence interval [CI] = 1.25‐1.62) and white race (OR = 1.35; 95% CI = 1.18‐1.55) were associated with high statin adherence. Follow‐up was 4.3 ± 2.6 years. Both low and partial adherence were associated with increase mortality (low adherence: adjusted hazard radio [HR] = 1.12; 95% CI = 1.01‐1.25; partial adherence: adjusted HR = 1.22; 95% CI = 1.12‐1.32). CONCLUSIONS: In older patients, aged 80 years or older, high adherence to statins after MI was associated with improved survival. This association may not have been due only to adherence to statins but to other related factors as well. Findings from this study may inform discussions on the potential benefits of statin adherence. J Am Geriatr Soc 67:2045–2049, 2019 [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Kaiser Permanente Southern California began offering a 4‐week supplemental benefit of home‐delivered meals to Medicare Advantage members after discharge from a hospitalization for heart failure and other medical conditions in 2021. The purpose of this study is to explore the associations between socioeconomic disadvantage and food insecurity with patient uptake of and satisfaction with the meals.Data for this cross‐sectional study were drawn from survey and electronic medical record data for members referred for the meals benefit (n = 6169) and linked to a hospitalization encounter (n = 2254) between January and December 2021. Uptake was assessed using vendor records; measures of socioeconomic status included the neighborhood deprivation index (NDI) and prior receipt of medical financial assistance (MFA) from the health system. Patients were invited to complete an email or phone survey about their satisfaction with the meals and food insecurity. Multivariable log‐binomial regression models were used to examine the association between socioeconomic disadvantage and food insecurity with meals uptake and satisfaction.Sixty‐two percent of patients referred for the benefit accepted the meals (mean age: 79 ± 9, 59% people of color). While there was no significant relationship between NDI and meals uptake (RR: 0.99, 95% CI: 0.92–1.07, p = 0.77), patients who received prior MFA were more likely to accept the meals (RR: 1.09, 95% CI: 1.02–1.16, p < 0.01). Sixty‐nine percent of patients who completed the survey (23% response rate) reported that meals were very or extremely helpful. Patients with food insecurity (29% of survey respondents) were more likely to report that the meals were helpful for their recovery compared to food secure patients (RR: 1.21, 95% CI: 1.09–1.35, p < 0.01).The home‐delivered meals appeared to be particularly utilized by and helpful to patients with greater financial strain and/or food insecurity, suggesting that supplemental benefits could be more targeted toward addressing unmet needs of vulnerable adults. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study is to report the prevalence, aetiology and clinical outcome of pregnant women with heart failure.Methods: This is a retrospective community-based cohort study that included pregnant women in the Kaiser Permanente Health System between 2003 and 2014. Women with heart failure were identified using International Classification of Disease, Ninth Revision codes. Medical records were manually reviewed to confirm diagnosis and adjudicate outcomes.Results: In a cohort of 385 935 pregnancies, 488 (0.13%) had a diagnosis of heart failure, corresponding to 126 cases per 100 000 pregnancies. Peripartum cardiomyopathy was the most common cause of heart failure, accounting for 333 (68.2%) cases. Preterm birth and caesarean delivery were more common in patients with heart failure. Neonatal death rate was higher in the heart failure group (1.0% vs 0.4%, p=0.03). Infants delivered to women with heart failure had lower birth weights (3112.0±774.0 g vs 3331.9±575.5 g, p<0.001) and lower Apgar score at 1 min (7.9±1.5 vs 8.3±1.1, p<0.001). Median follow-up was 6.2 years (IQR 3.2-9.2). During follow-up, 7 (1.4%) in the heart failure group and 423 (0.11%) in the control group died. Heart failure was associated with a 7.7-fold increase risk of death (adjusted HR 7.7, 95% CI 3.6 to 16.4, p<0.001).Conclusion: Heart failure during pregnancy is associated with unfavourable fetal outcomes including prematurity and low birth weight. While the overall mortality rate was low, pregnant women with heart failure carried an excess risk of death compared with controls. [ABSTRACT FROM AUTHOR]

Beta-blockers are one of the most commonly prescribed classes of antihypertensive medications during pregnancy. Previous studies reported an association between beta-blocker exposure and intrauterine growth restriction. Whether some beta-blocker subtypes may be associated with higher risk is not known. This is a retrospective cohort study of pregnant women exposed to beta-blockers in the Kaiser Permanente Southern California Region between 2003 and 2014. Logistic regression models were used to evaluate association between exposure to different beta-blocker agents and risk of low fetal birth weights. In a cohort of 379 238 singleton pregnancies, 4847 (1.3%) were exposed to beta-blockers. The four most commonly prescribed beta-blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489), and metoprolol (n = 324). Mean birth weight and % low birth weight (<2500 g) were 2926 ± 841 g and 24.4% for labetalol, 3058 ± 748 g and 18.0% for atenolol, 3163 ± 702 g and 13.3% for metoprolol, 3286 ± 651 g and 7.6% for propranolol, and 3353 ± 554 g and 5.2% for non-exposed controls. Exposure to atenolol and labetalol were associated with increased risks of infant born small for gestational age (SGA) (atenolol: adjusted OR 2.4, 95% CI: 1.7-3.3; labetalol: adjusted OR 2.9, 95% CI: 2.6-3.2). Risk of SGA associated with metoprolol or propranolol exposure was not significantly different from the non-exposed group (metoprolol: adjusted OR 1.5, 95% CI: 0.9-2.3; propranolol: adjusted OR 1.3, 95% CI: 0.9-1.9). Association between beta-blocker exposure and SGA does not appear to be a class effect. Variations in pharmacodynamics and confounding by indication may explain these findings. [ABSTRACT FROM AUTHOR]

Context: Many patients with ductal carcinoma in situ (DCIS) receive treatment that is too extensive. Objective: To take a holistic approach in comparing the effectiveness in cancer prevention between mastectomy and breast-conserving surgery (BCS) for patients with DCIS. Design: Female Kaiser Permanente Southern California members who underwent surgery for treatment of single primary DCIS from 2004 to 2014 were identified by the Kaiser Permanente Southern California cancer registry and HealthConnect database. Method: Two-stage residual inclusion with the surgeon's preference of surgical procedure type as the instrumental variable was used to examine the effect of surgical choice on DCIS recurrence, breast cancer progression, and other cancer progression. Traditional Cox proportional hazards models were used for comparison. Results: Of qualified subjects, 72.2% underwent BCS and 27.8% underwent mastectomy. Patients were likelier to receive BCS if their surgeon preferred to perform BCS in the past 5 years (odds ratio = 1.02, 95% confidence interval = 1.02-1.03). Although traditional Cox proportional hazards models suggested an association between BCS and higher risk of DCIS recurrence, no significant effect was observed when we adjusted for endogeneity. Neither model showed significant differences between mastectomy and BCS in progression of any cancer. Conclusion: No significant benefit was observed with a more aggressive surgical procedure in preventing DCIS recurrence or cancer progression in a diverse population. Many patients with DCIS could benefit from BCS with preservation of their body image. Breast conservation followed-up with cancer surveillance is a rational approach to ensure affordable, effective care for patients with DCIS. [ABSTRACT FROM AUTHOR]

This retrospective cohort study of 95 957 patients from a large integrated healthcare organization was conducted to examine whether the frequency and intervals between outpatient encounters were associated with achieving blood pressure (BP) control. Patients were followed up until they were censored or achieved BP control up to 1 year. Additionally, this study examined the time to BP control. On average, follow-up was significantly longer in patients with uncontrolled BP at 292.9 days compared with 232.2 days in those with BP control. The controlled BP group had significantly more encounters on average compared with the uncontrolled BP group (4.1 vs 3.1, standardized difference 0.33). As the number of days increased between encounters from the 1 to < 14 days, there was a consistently lower likelihood of achieving BP control. Encounter intervals of ≥180 days were associated with the lowest likelihood of achieving BP control. These findings suggest that there may be an optimal number of encounters to benefit patients with hypertension. [ABSTRACT FROM AUTHOR]

Autocrine VEGF is necessary for endothelial survival, although the cellular mechanisms supporting this function are unknown. Here, we show that -- even after full differentiation and maturation -- continuous expression of VEGF by endothelial cells is needed to sustain vascular integrity and cellular viability. Depletion of VEGF from the endothelium results in mitochondria fragmentation and suppression of glucose metabolism, leading to increased autophagy that contributes to cell death. Gene-expression profiling showed that endothelial VEGF contributes to the regulation of cell cycle and mitochondrial gene clusters, as well as several -- but not all -- targets of the transcription factor FOXO1. Indeed, VEGF-deficient endothelium in vitro and in vivo showed increased levels of FOXO1 protein in the nucleus and cytoplasm. Silencing of FOXO1 in VEGF-depleted cells reversed expression profiles of several of the gene clusters that were de-regulated in VEGF knockdown, and rescued both cell death and autophagy phenotypes. Our data suggest that endothelial VEGF maintains vascular homeostasis through regulation of FOXO1 levels, thereby ensuring physiological metabolism and endothelial cell survival. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Tocilizumab (TCZ) is a biological agent used for the treatment of moderate to severe rheumatoid arthritis (RA). In the present systematic literature review and meta-analysis, we provide an update on the efficacy and safety of TCZ and our clinical comments for the treatment of RA. Methods: We searched PubMed for randomized, double-blind, placebo-controlled clinical trials investigating the effects of TCZ on RA. The initial search included articles from 1966 to December 2011. The search was subsequently updated in April 2013. Studies had to report clinical efficacy using American College of Rheumatology (ACR) 20, 50, and 70 disease measures. The studies included participants who were 18 years of age and who met the ACR 1987 revised criteria for RA for 6 months or longer. Two reviewers independently abstracted the data, and disagreement was resolved by discussion with a third reviewer. Outcome measures were analyzed as odds ratio using the Mantel–Haenszel estimator under a random effects model to account for heterogeneity in intervention effects between trials. Descriptive statistics were used to compare adverse events. Results: After reviewing and culling, 8 randomized, controlled, double-blind studies were included in the efficacy meta-analysis. TCZ 8mg/kg was statistically favored over TCZ 4mg/kg or placebo regarding ACR responses. Clinically significant adverse events that occurred with TCZ treatment included infections, lipid and liver function test abnormalities, and gastrointestinal side effects, all of which were more common with TCZ. Conclusions: This meta-analysis supports the use of TCZ as an appropriate treatment for moderate to severe RA as monotherapy and combination therapy. Close monitoring for significant adverse events is required when treating patients with TCZ. Future long-term trials should focus further on safety of this agent. [Copyright &y& Elsevier]

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and probably also non-Hodgkin's B-cell lymphoma. The molecular mechanisms of HCV-associated carcinogenesis are unknown. Here we demonstrated that peripheral blood mononuclear cells obtained from hepatitis C patients and hepatocytes infected with HCV in vitro showed frequent chromosomal polyploidy. HCV infection or the expression of viral core protein alone in hepatocyte culture or transgenic mice inhibited mitotic spindle checkpoint function because of reduced Rb transcription and enhanced E2F-1 and Mad2 expression. The silencing of E2F-1 by RNA interference technology restored the function of mitotic checkpoint in core-expressing cells. Taken together, these data suggest that HCV infection may inhibit the mitotic checkpoint to induce polyploidy, which likely contributes to neoplastic transformation. [ABSTRACT FROM AUTHOR]