Cost-effectiveness of a Digital Health Intervention for Acute Myocardial Infarction Recovery.

BACKGROUND: Acute myocardial infarction (AMI) is a common cause of hospital admissions, readmissions, and mortality worldwide. Digital health interventions (DHIs) that promote self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction may improve health outcomes in this population. The "Corrie" DHI consists of a smartphone application, smartwatch, and wireless blood pressure monitor to support medication tracking, education, vital signs monitoring, and care coordination. We aimed to assess the cost-effectiveness of this DHI plus standard of care in reducing 30-day readmissions among AMI patients in comparison to standard of care alone. METHODS: A Markov model was used to explore cost-effectiveness from the hospital perspective. The time horizon of the analysis was 1 year, with 30-day cycles, using inflation-adjusted cost data with no discount rate. Currencies were quantified in US dollars, and effectiveness was measured in quality-adjusted life-years (QALYs). The results were interpreted as an incremental cost-effectiveness ratio at a threshold of $100,000 per QALY. Univariate sensitivity and multivariate probabilistic sensitivity analyses tested model uncertainty. RESULTS: The DHI reduced costs and increased QALYs on average, dominating standard of care in 99.7% of simulations in the probabilistic analysis. Based on the assumption that the DHI costs $2750 per patient, use of the DHI leads to a cost-savings of $7274 per patient compared with standard of care alone. CONCLUSIONS: Our results demonstrate that this DHI is cost-saving through the reduction of risk for all-cause readmission following AMI. DHIs that promote improved adherence with guideline-based health care can reduce hospital readmissions and associated costs.

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

BACKGROUND: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. METHODS: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. RESULTS: Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors. CONCLUSIONS: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer.

Genetic variation in one-carbon metabolism in relation to genome-wide DNA methylation in breast tissue from heathy women.

Single nucleotide polymorphisms (SNPs) in one-carbon metabolism genes and lifestyle factors (alcohol drinking and breast folate) may be determinants of whole-genome methylation in the breast. DNA methylation profiling was performed using the Illumina Infinium HumanMethylation450 BeadChip in 81 normal breast tissues from women undergoing reduction mammoplasty and no history of cancer. ANCOVA, adjusting for age, race and BMI, was used to identify differentially-methylated (DM) CpGs. Gene expression, by the Affymetrix GeneChip Human Transcriptome Array 2.0, was correlated with DM. Biological networks of DM genes were assigned using Ingenuity Pathway Analysis. Fifty-seven CpG sites were DM in association with eight SNPs in FTHFD, MTHFD1, MTHFR, MTR, MTRR, and TYMS (P <5.0 x 10-5); 56% of the DM CpGs were associated with FTHFD SNPs, including DM within FTHFD. Gene expression was negatively correlated with FTHFD methylation (r=-0.25, P=0.017). Four DM CpGs identified by SNPs in MTRR, MTHFR, and FTHFD were significantly associated with alcohol consumption and/or breast folate. The top biological network of DM CpGs was associated with Energy Production, Molecular Transportation, and Nucleic Acid Metabolism. This is the first comprehensive study of the association between SNPs in one-carbon metabolism genes and genome-wide DNA methylation in normal breast tissues. These SNPs, especially FTHFD, as well as alcohol intake and folate exposure, appear to affect DM in breast tissues of healthy women. The finding that SNPs in FTHFD and MTR are associated with their own methylation is novel and highlights a role for these SNPs as cis-methylation quantitative trait loci.

Persistent alterations of gene expression profiling of human peripheral blood mononuclear cells from smokers.

The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke, effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacco products. We assessed the effects of smoking on the gene expression using human cell cultures and blood from a cross-sectional study. We profiled global transcriptional changes in cultured smokers' peripheral blood mononuclear cells (PBMCs) treated with cigarette smoke condensate (CSC) in vitro (n = 7) and from well-characterized smokers' blood (n = 36). ANOVA with adjustment for covariates and Pearson correlation were used for statistical analysis in this study. CSC in vitro altered the expression of 1 178 genes (177 genes with > 1.5-fold-change) at P < 0.05. In vivo, PBMCs of heavy and light smokers differed for 614 genes (29 with > 1.5-fold-change) at P < 0.05 (309 remaining significant after adjustment for age, race, and gender). Forty-one genes were persistently altered both in vitro and in vivo, 22 having the same expression pattern reported for non-small cell lung cancer. Our data provides evidence that persistent alterations of gene expression in vitro and in vivo may relate to carcinogenic effects of cigarette smoke, and the identified genes may serve as potential biomarkers for cancer. The use of an in vitro model to corroborate results from human studies provides a novel way to understand human exposure and effect. © 2015 Wiley Periodicals, Inc.

Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses.

PURPOSE: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups. METHODS: Patients with dMMR CRC identified by immunohistochemistry staining and treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients' charts were accessed for information on pathology, germ-line MMR mutation testing, and clinical course. RESULTS: A total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 74%). Patients with LS were younger, more often male, presented more often with stage III disease, and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer-specific survival (CSS) between the groups; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis. CONCLUSION: CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.Genet Med 18 9, 863-868.

Validation of ZAP-70 methylation and its relative significance in predicting outcome in chronic lymphocytic leukemia.

ZAP-70 methylation 223 nucleotides downstream of transcription start (CpG+223) predicts outcome in chronic lymphocytic leukemia (CLL), but its impact relative to CD38 and ZAP-70 expression or immunoglobulin heavy chain variable region (IGHV) status is uncertain. Additionally, standardizing ZAP-70 expression analysis has been unsuccessful. CpG+223 methylation was quantitatively determined in 295 untreated CLL cases using MassARRAY. Impact on clinical outcome vs CD38 and ZAP-70 expression and IGHV status was evaluated. Cases with low methylation (<20%) had significantly shortened time to first treatment (TT) and overall survival (OS) (P < .0001). For TT, low methylation defined a large subset of ZAP-70 protein-negative cases with significantly shortened TT (median, 8.0 vs 3.9 years for high vs low methylation; hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.25-0.74). Conversely, 16 ZAP-70 protein-positive cases with high methylation had poor outcome (median, 1.1 vs 2.3 years for high vs low methylation; HR = 1.62; 95% CI, 0.87-3.03). For OS, ZAP-70 methylation was the strongest risk factor; CD38 and ZAP-70 expression or IGHV status did not significantly improve OS prediction. A pyrosequencing assay was established that reproduced the MassARRAY data (κ coefficient > 0.90). Thus, ZAP-70 CpG+223 methylation represents a superior biomarker for TT and OS that can be feasibly measured, supporting its use in risk-stratifying CLL.

Sex-related DNA methylation is associated with inflammation and gene expression in the lungs of healthy individuals.

Lung cancer exhibits sex-biased molecular characteristics and epidemiological trends, suggesting a need for sex-specific approaches to understanding its etiology and treatment. DNA methylation alterations play critical roles in lung carcinogenesis and may serve as valuable biomarkers for precision medicine strategies. We employed the Infinium MethylationEPIC array to identify autosomal sex-related differentially methylated CpG sites (DM-CpGs) in lung epithelium of healthy individuals (32 females and 37 males) while controlling for age, BMI, and tobacco use. We correlated DM-CpGs with gene expression in lung epithelium and immune responses in bronchoalveolar lavage. We validated these DM-CpGs in lung tumors and adjacent normal tissue from The Cancer Genome Atlas (TCGA). Among 522 identified DM-CpGs, 61% were hypermethylated in females, predominantly located in promoter regions. These DM genes were implicated in cell-to-cell signaling, cellular function, transport, and lipid metabolism. Correlation analysis revealed sex-specific patterns between DM-CpGs and gene expression. Additionally, several DM-CpGs were correlated significantly with cytokines (IL-1ß, IL-4, IL-12p70, and IFN-γ), macrophage, and lymphocyte counts. Also, some DM-CpGs were observed in TCGA lung adenocarcinoma, squamous cell carcinoma, and adjacent normal tissues. Our findings highlight sex-specific DNA methylation patterns in healthy lung epithelium and their associations with lung gene expression and lung immune biomarkers. These findings underscore the potential role of lung sex-related CpGs as epigenetic predispositions influencing sex disparities in lung cancer risk and outcomes, warranting further investigation for personalized lung cancer management strategies.

Untargeted Metabolomics and Body Mass in Adolescents: A Cross-Sectional and Longitudinal Analysis.

Obesity in children and adolescents has increased globally. Increased body mass index (BMI) during adolescence carries significant long-term adverse health outcomes, including chronic diseases such as cardiovascular disease, stroke, diabetes, and cancer. Little is known about the metabolic consequences of changes in BMI in adolescents outside of typical clinical parameters. Here, we used untargeted metabolomics to assess changing BMI in male adolescents. Untargeted metabolomic profiling was performed on urine samples from 360 adolescents using UPLC-QTOF-MS. The study includes a baseline of 235 subjects in a discovery set and 125 subjects in a validation set. Of them, a follow-up of 81 subjects (1 year later) as a replication set was studied. Linear regression analysis models were used to estimate the associations of metabolic features with BMI z-score in the discovery and validation sets, after adjusting for age, race, and total energy intake (kcal) at false-discovery-rate correction (FDR) ≤ 0.1. We identified 221 and 16 significant metabolic features in the discovery and in the validation set, respectively. The metabolites associated with BMI z-score in validation sets are glycylproline, citrulline, 4-vinylsyringol, 3'-sialyllactose, estrone sulfate, carnosine, formiminoglutamic acid, 4-hydroxyproline, hydroxyprolyl-asparagine, 2-hexenoylcarnitine, L-glutamine, inosine, N-(2-Hydroxyphenyl) acetamide glucuronide, and galactosylhydroxylysine. Of those 16 features, 9 significant metabolic features were associated with a positive change in BMI in the replication set 1 year later. Histidine and arginine metabolism were the most affected metabolic pathways. Our findings suggest that obesity and its metabolic outcomes in the urine metabolome of children are linked to altered amino acids, lipid, and carbohydrate metabolism. These identified metabolites may serve as biomarkers and aid in the investigation of obesity's underlying pathological mechanisms. Whether these features are associated with the development of obesity, or a consequence of changing BMI, requires further study.

A Pilot Cross-Sectional Study of Immunological and Microbiome Profiling Reveals Distinct Inflammatory Profiles for Smokers, Electronic Cigarette Users, and Never-Smokers.

Smokers (SM) have increased lung immune cell counts and inflammatory gene expression compared to electronic cigarette (EC) users and never-smokers (NS). The objective of this study is to further assess associations for SM and EC lung microbiomes with immune cell subtypes and inflammatory gene expression in samples obtained by bronchoscopy and bronchoalveolar lavage (n = 28). RNASeq with the CIBERSORT computational algorithm were used to determine immune cell subtypes, along with inflammatory gene expression and microbiome metatranscriptomics. Macrophage subtypes revealed a two-fold increase in M0 (undifferentiated) macrophages for SM and EC users relative to NS, with a concordant decrease in M2 (anti-inflammatory) macrophages. There were 68, 19, and 1 significantly differentially expressed inflammatory genes (DEG) between SM/NS, SM/EC users, and EC users/NS, respectively. CSF-1 and GATA3 expression correlated positively and inversely with M0 and M2 macrophages, respectively. Correlation profiling for DEG showed distinct lung profiles for each participant group. There were three bacteria genera-DEG correlations and three bacteria genera-macrophage subtype correlations. In this pilot study, SM and EC use were associated with an increase in undifferentiated M0 macrophages, but SM differed from EC users and NS for inflammatory gene expression. The data support the hypothesis that SM and EC have toxic lung effects influencing inflammatory responses, but this may not be via changes in the microbiome.

Accelerated epigenetic age, inflammation, and gene expression in lung: comparisons of smokers and vapers with non-smokers.

BACKGROUND: Cigarette smoking and aging are the main risk factors for pulmonary diseases, including cancer. Epigenetic aging may explain the relationship between smoking, electronic cigarette vaping, and pulmonary health. No study has examined smoking and vaping-related epigenetic aging in relation to lung biomarkers. METHODS: Lung epigenetic aging measured by DNA methylation (mAge) and its acceleration (mAA) was assessed in young (age 21-30) electronic cigarette vapers (EC, n = 14, including 3 never-smoking EC), smokers (SM, n = 16), and non-EC/non-SM (NS, n = 39). We investigated relationships of mAge estimates with chronological age (Horvath-mAge), lifespan/mortality (Grim-mAge), telomere length (TL-mAge), smoking/EC history, urinary biomarkers, lung cytokines, and transcriptome. RESULTS: Compared to NS, EC and SM had significantly older Grim-mAge, shorter TL-mAge, significantly accelerated Grim-mAge and decelerated TL-mAge. Among SM, Grim-mAA was associated with nicotine intake and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). For EC, Horvath-mAA was significantly correlated with puffs per day. Overall, cytokines (IL-1ß, IL-6, and IL-8) and 759 transcripts (651 unique genes) were significantly associated with Grim-mAA. Grim-mAA-associated genes were highly enriched in immune-related pathways and genes that play a role in the morphology and structures of cells/tissues. CONCLUSIONS: Faster lung mAge for SM is consistent with prior studies of blood. Faster lung mAge for EC compared to NS indicates possible adverse pulmonary effects of EC on biological aging. Our findings support further research, particularly on epigenetic markers, on effects of smoking and vaping on pulmonary health. Given that most EC are former smokers, further study is needed to understand unique effects of electronic cigarettes on biological aging.

Case report: olaparib use in metastatic lung adenocarcinoma with BRCA2 pathogenic variant.

Poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in malignancies associated with germline BRCA1 or BRCA2 pathogenic variants, such as breast, ovarian, prostate, and pancreatic cancer. In malignancies not associated with germline BRCA1 or BRCA2 pathogenic variants, the therapeutic relevance of PARP inhibitors is less clear. Non-small-cell lung cancer (NSCLC) is known to demonstrate somatic alterations in BRCA1 or BRCA2 gene. The current report is on a gentleman with metastatic lung adenocarcinoma with a somatic BRCA2 pathogenic variant, who was effectively treated with olaparib. Furthermore, we discuss the existing data for use of PARP inhibitors in NSCLC. This study highlights the utility of next-generation sequencing in identifying gene mutations and demonstrates how such information can be used to select targeted therapies in patients with actionable molecular alterations.

Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking.

The microbiome has increasingly been linked to cancer. Little is known about the lung and oral cavity microbiomes in smokers, and even less for electronic cigarette (EC) users, compared with never-smokers. In a cross-sectional study (n = 28) of smokers, EC users, and never-smokers, bronchoalveolar lavage and saliva samples underwent metatranscriptome profiling to examine associations with lung and oral microbiomes. Pairwise comparisons assessed differentially abundant bacteria species. Total bacterial load was similar between groups, with no differences in bacterial diversity across lung microbiomes. In lungs, 44 bacteria species differed significantly (FDR < 0.1) between smokers/never-smokers, with most decreased in smokers. Twelve species differed between smokers/EC users, all decreased in smokers of which Neisseria sp. KEM232 and Curvibacter sp. AEP1-3 were observed. Among the top five decreased species in both comparisons, Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae were observed. In the oral microbiome, 152 species were differentially abundant for smokers/never-smokers, and 17 between smokers/electronic cigarette users, but only 21 species were differentially abundant in both the lung and oral cavity. EC use is not associated with changes in the lung microbiome compared with never-smokers, indicating EC toxicity does not affect microbiota. Statistically different bacteria in smokers compared with EC users and never-smokers were almost all decreased, potentially due to toxic effects of cigarette smoke. The low numbers of overlapping oral and lung microbes suggest that the oral microbiome is not a surrogate for analyzing smoking-related effects in the lung. PREVENTION RELEVANCE: The microbiome affects cancer and other disease risk. The effects of e-cig usage on the lung microbiome are essentially unknown. Given the importance of lung microbiome dysbiosis populated by oral species which have been observed to drive lung cancer progression, it is important to study effects of e-cig use on microbiome.

Lung mitochondrial DNA copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers.

BACKGROUND: Mitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, and is linked to nuclear DNA methylation and gene expression. Increased mtCN in the blood is associated with smoking and respiratory disease, but has received little attention for target organ effects for smoking or electronic cigarette (EC) use. METHODS: Bronchoscopy biospecimens from healthy EC users, smokers (SM), and never-smokers (NS) were assessed for associations of mtCN with mtDNA point mutations, immune responses, nuclear DNA methylation and gene expression using linear regression. Ingenuity pathway analysis was used for enriched pathways. GEO and TCGA respiratory disease datasets were used to explore the involvement of mtCN-associated signatures. FINDINGS: mtCN was higher in SM than NS, but EC was not statistically different from either. Overall there was a negative association of mtCN with a point mutation in the D-loop but no difference within groups. Positive associations of mtCN with IL-2 and IL-4 were found in EC only. mtCN was significantly associated with 71,487 CpGs and 321 transcripts. 263 CpGs were correlated with nearby transcripts for genes enriched in the immune system. EC-specific mtCN-associated-CpGs and genes were differentially expressed in respiratory diseases compared to controls, including genes involved in cellular movement, inflammation, metabolism, and airway hyperresponsiveness. INTERPRETATION: Smoking may elicit a lung toxic effect through mtCN. While the impact of EC is less clear, EC-specific associations of mtCN with nuclear biomarkers suggest exposure may not be harmless. Further research is needed to understand the role of smoking and EC-related mtCN on lung disease risks. FUNDING: The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds.

Correction: Technical Guidance for Clinicians Interested in Partnering With Engineers in Mobile Health Development and Evaluation.

[This corrects the article DOI: 10.2196/14124.].

Heart rate trajectories in patients recovering from acute myocardial infarction: A longitudinal analysis of Apple Watch heart rate recordings.

Background: Using mobile health, vital signs such as heart rate (HR) can be used to assess a patient's recovery process from acute events including acute myocardial infarction (AMI). Objective: We aimed to characterize clinical correlates associated with HR change in the subacute period among patients recovering from AMI. Methods: HR measurements were collected from 91 patients (4447 HR recordings) enrolled in the MiCORE study using the Apple Watch and Corrie smartphone application. Mixed regression models were used to estimate the associations of patient-level characteristics during hospital admission with HR changes over 30 days postdischarge. Results: The mean daily HR at admission was 78.0 beats per minute (bpm) (95% confidence interval 76.1 to 79.8), declining 0.2 bpm/day (-0.3 to -0.1) under a linear model of HR change. History of coronary artery bypass graft, history of depression, or being discharged on anticoagulants was associated with a higher admission HR. Having a history of hypertension, type 2 diabetes mellitus (T2DM), or hyperlipidemia was associated with a slower decrease in HR over time, but not with HR during admission. Conclusion: While a declining HR was observed in AMI patients over 30 days postdischarge, patients with hypertension, T2DM, or hyperlipidemia showed a slower decrease in HR relative to their counterparts. This study demonstrates the feasibility of using wearables to model the recovery process of patients with AMI and represents a first step in helping pinpoint patients vulnerable to decompensation.

Clinicians for CARE: A Systematic Review and Meta-Analysis of Interventions to Support Caregivers of Patients With Heart Disease.

Background Caregivers provide critical support for patients with chronic diseases, including heart disease, but often experience caregiver stress that negatively impacts their health, quality of life, and patient outcomes. We aimed to inform health care teams on an evidence-based approach to supporting the caregivers of patients with heart disease. Methods and Results We conducted a systematic review and meta-analysis of randomized controlled trials written in English that evaluated interventions to support caregivers of patients with heart disease. We identified 15,561 articles as of April 2, 2020 from 6 databases; of which 20 unique randomized controlled trials were evaluated, representing a total of 1570 patients and 1776 caregivers. Most interventions focused on improving quality of life, and reducing burden, depression, and anxiety; 85% (17 of 20) of the randomized controlled trials provided psychoeducation for caregivers. Interventions had mixed results, with moderate non-significant effects observed for depression (Hedges' g=-0.64; 95% CI, -1.34 to 0.06) and burden (Hedges' g=-0.51; 95% CI, -2.71 to 1.70) at 2 to 4 months postintervention and small non-significant effects observed for quality of life and anxiety. These results were limited by the heterogeneity of outcome measures and intervention delivery methods. A qualitative synthesis of major themes of the interventions resulted in clinical recommendations represented with the acronym "CARE" (Caregiver-Centered, Active engagement, Reinforcement, Education). Conclusions This systematic review highlights the need for greater understanding of the challenges faced by caregivers and the development of guidelines to help clinicians address those challenges. More research is necessary to develop clinical interventions that consistently improve caregiver outcomes.

Digital Health Intervention in Acute Myocardial Infarction.

BACKGROUND: Thirty-day readmissions among patients with acute myocardial infarction (AMI) contribute to the US health care burden of preventable complications and costs. Digital health interventions (DHIs) may improve patient health care self-management and outcomes. We aimed to determine if patients with AMI using a DHI have lower 30-day unplanned all-cause readmissions than a historical control. METHODS: This nonrandomized controlled trial with a historical control, conducted at 4 US hospitals from 2015 to 2019, included 1064 patients with AMI (DHI n=200, control n=864). The DHI integrated a smartphone application, smartwatch, and blood pressure monitor to support guideline-directed care during hospitalization and through 30-days post-discharge via (1) medication reminders, (2) vital sign and activity tracking, (3) education, and (4) outpatient care coordination. The Patient Activation Measure assessed patient knowledge, skills, and confidence for health care self-management. All-cause 30-day readmissions were measured through administrative databases. Propensity score-adjusted Cox proportional hazard models estimated hazard ratios of readmission for the DHI group relative to the control group. RESULTS: Following propensity score adjustment, baseline characteristics were well-balanced between the DHI versus control patients (standardized differences <0.07), including a mean age of 59.3 versus 60.1 years, 30% versus 29% Women, 70% versus 70% White, 54% versus 54% with private insurance, 61% versus 60% patients with a non ST-elevation myocardial infarction, and 15% versus 15% with high comorbidity burden. DHI patients were predominantly in the highest levels of patient activation for health care self-management (mean score 71.7±16.6 at 30 days). The DHI group had fewer all-cause 30-day readmissions than the control group (6.5% versus 16.8%, respectively). Adjusting for hospital site and a propensity score inclusive of age, sex, race, AMI type, comorbidities, and 6 additional confounding factors, the DHI group had a 52% lower risk for all-cause 30-day readmissions (hazard ratio, 0.48 [95% CI, 0.26-0.88]). Similar results were obtained in a sensitivity analysis employing propensity matching. CONCLUSIONS: Our results suggest that in patients with AMI, the DHI may be associated with high patient activation for health care self-management and lower risk of all-cause unplanned 30-day readmissions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03760796.

Lipid laden macrophages and electronic cigarettes in healthy adults.

BACKGROUND: An outbreak of E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) with significant morbidity and mortality was reported in 2019. While most patients with EVALI report vaping tetrahydrocannabinol (THC) oils contaminated with vitamin E acetate, a subset report only vaping with nicotine-containing electronic cigarettes (e-cigs). Whether or not e-cigs cause EVALI, the outbreak highlights the need for identifying long term health effects of e-cigs. EVALI pathology includes alveolar damage, pneumonitis and/or organizing pneumonia, often with lipid-laden macrophages (LLM). We assessed LLM in the lungs of healthy smokers, e-cig users, and never-smokers as a potential marker of e-cig toxicity and EVALI. METHODS: A cross-sectional study using bronchoscopy was conducted in healthy smokers, e-cig users, and never-smokers (n = 64). LLM, inflammatory cell counts, and cytokines were determined in bronchial alveolar fluids (BAL). E-cig users included both never-smokers and former light smokers. FINDINGS: High LLM was found in the lungs of almost all smokers and half of the e-cig users, but not those of never-smokers. LLM were not related to THC exposure or smoking history. LLM were significantly associated with inflammatory cytokines IL-4 and IL-10 in e-cig users, but not smoking-related cytokines. INTERPRETATION: This is the first report of lung LLM comparing apparently healthy smokers, e-cig users, and never-smokers. LLM are not a specific marker for EVALI given the frequent positivity in smokers; whether LLMs are a marker of lung inflammation in some e-cig users requires further study. FUNDING: The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds.

Early blood pressure assessment after acute myocardial infarction: Insights using digital health technology.

OBJECTIVE: There is rising interest in digital health in preventive cardiology, particularly for blood pressure (BP) management. In a digital health study of early BP assessment following acute myocardial infarction (AMI), we sought to examine feasibility and the (1) proportion of post-AMI patients with controlled BP and hypotension, and (2) association between prior cardiovascular disease (CVD) and BP post-AMI. METHODS: In this substudy of the parent Myocardial infarction, COmbined-device, Recovery Enhancement (MiCORE) study, type 1 AMI patients were enrolled between October 2017 and April 2019. Participants self-monitored their BP through 30 days after hospital discharge using an FDA-approved wireless BP monitor connected with a smartphone application. Linear mixed-effects models assessed the association between prior CVD and BP trajectory post-discharge, adjusting for antihypertensive medications and a propensity score inclusive of CVD risk factors. RESULTS: Sixty-eight AMI patients (mean age 58 â€‹± â€‹10 years, 75% male, 68% white race, 68% history of hypertension, 24% prior CVD) provided 2638 measurements over 30 days. The percentage of BP control <130/80 â€‹mmHg was 59.6% (95% CI: 54.3-64.9%) and <140/90 â€‹mmHg was 83.7% (95% CI: 80.3-87.2%). The percentage of systolic BP â€‹<90 â€‹mmHg was 1.1% (95% CI: 0.17-2.0%) and the percentage of diastolic BP â€‹<60 â€‹mmHg was 3.9% (95% CI: 2.6-5.2%). Prior CVD was associated with 12.2 â€‹mmHg higher mean daily systolic BP during admission (95% CI: 3.5-20.9 â€‹mmHg), which persisted over follow-up. There was no association between prior CVD and diastolic BP. CONCLUSION: The digital health program was feasible and ~40% of post-AMI patients who engaged in it had uncontrolled BP according to recent guideline cutpoints, while hypotension occurred rarely. The gap in BP control was especially large in patients in whom AMI represented recurrent CVD. These data suggest an opportunity for more aggressive secondary prevention early after MI as care models integrate digital health.

Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.

Electronic cigarette (e-cig) use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a 4-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary PG. Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, miRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL8, IL13, and TNFα), although the absolute magnitude of changes was small. There were no significant changes in mRNA or miRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.