The association between cumulative exposure to PM2.5 and DNA methylation measured using methyl-capture sequencing among COPD patients.

BACKGROUND: Particulate matter with a diameter of < 2.5 µm (PM2.5) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM2.5 exposure and DNA methylation in CpG islands as well as explore the associated gene pathways. METHODS: A total of 95 male patients with chronic obstructive pulmonary disease (COPD) were enrolled in this study. PM2.5 concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM2.5 exposure levels were calculated for short-term (7 days), mid-term (35 days), and long-term (90 days). DNA methylation analysis was performed on the blood samples, which, after PCR amplification and hybridization, were finally sequenced using an Illumina NovaSeq 6000 system. Correlation between PM2.5 exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM2.5 exposure to identify the relevant biological functions or pathways. RESULTS: The number of CpG sites showing differential methylation was 36, 381, and 182 for the short-, mid-, and long-term indoor models, respectively, and 3, 98, and 28 for the short-, mid-, and long-term estimated exposure models, respectively. The representative genes were TMTC2 (p = 1.63 × 10-3, R2 = 0.656), GLRX3 (p = 1.46 × 10-3, R2 = 0.623), DCAF15 (p = 2.43 × 10-4, R2 = 0.623), CNOT6L (p = 1.46 × 10-4, R2 = 0.609), BSN (p = 2.21 × 10-5, R2 = 0.606), and SENP6 (p = 1.59 × 10-4, R2 = 0.604). Functional enrichment analysis demonstrated that the related genes were mostly associated with pathways related to synaptic transmission in neurodegenerative diseases and cancer. CONCLUSION: A significant association was observed between PM2.5 exposure and DNA methylation upon short-term exposure, and the extent of DNA methylation was the highest upon mid-term exposure. Additionally, various pathways related to neurodegenerative diseases and cancer were associated with patients with COPD. GOV IDENTIFIER: NCT04878367.

Isolated respiratory tract microorganisms and clinical characteristics in asthma exacerbation of obese patients: a multicenter study.

BACKGROUND: Viral infection is a risk factor for asthma exacerbation (AE). However, bacterial infections related to AE in adults are poorly known. On the other hand, obese patients with asthma have their own clinical and biological characteristics compared with non-obese patients. METHODS: We investigated the differences in isolated pathogens for AE between obese and non-obese patients with asthma. We included 407 patients with AE from 24 medical centers in Korea. Microorganisms isolated from culture, RT-PCR or serologic tests using lower respiratory tract specimens were retrospectively investigated. RESULTS: A total of 171 obese and 236 non-obese patients with asthma were included for analysis. Compared to non-obese patients, obese patients were associated with women (77.2% vs. 63.6%), never smoker (82.5% vs. 73.9%), shorter duration of asthma (7.9 ± 8.4 vs. 10.5 ± 10.1 years), less history of pulmonary tuberculosis (8.8% vs. 17.4%), and more comorbidity of allergic rhinitis (48.5% vs. 0.8%). Viral and/or bacterial infections were detected in 205 patients (50.4%) with AE. The numbers of patients with viral only, bacterial only, or both infections were 119, 49, and 37, respectively. The most commonly isolated bacterium was Streptococcus pneumoniae, followed by Pseudomonas aeruginosa and Chlamydia pneumoniae. Obese patients showed a lower incidence of Chlamydia pneumoniae infection. In the non-obese group, bacterial infection, especially Chlamydia pneumoniae infection, was significantly associated with the duration of systemic corticosteroid use (13.6 ± 19.8 vs. 9.7 ± 6.7 days, p = 0.049). CONCLUSION: Bacterial infection was associated with a longer period of corticosteroid use in the non-obese group. Acute Chlamydia pneumoniae infection was less associated with obese patients with AE. Further well-designed studies are needed to evaluate microorganisms and the efficacy of antibiotics in patients with AE.

Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement.

Importance: Among all US women, breast cancer is the second most common cancer and the second most common cause of cancer death. In 2023, an estimated 43 170 women died of breast cancer. Non-Hispanic White women have the highest incidence of breast cancer and non-Hispanic Black women have the highest mortality rate. Objective: The USPSTF commissioned a systematic review to evaluate the comparative effectiveness of different mammography-based breast cancer screening strategies by age to start and stop screening, screening interval, modality, use of supplemental imaging, or personalization of screening for breast cancer on the incidence of and progression to advanced breast cancer, breast cancer morbidity, and breast cancer-specific or all-cause mortality, and collaborative modeling studies to complement the evidence from the review. Population: Cisgender women and all other persons assigned female at birth aged 40 years or older at average risk of breast cancer. Evidence Assessment: The USPSTF concludes with moderate certainty that biennial screening mammography in women aged 40 to 74 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening mammography in women 75 years or older and the balance of benefits and harms of supplemental screening for breast cancer with breast ultrasound or magnetic resonance imaging (MRI), regardless of breast density. Recommendation: The USPSTF recommends biennial screening mammography for women aged 40 to 74 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of supplemental screening for breast cancer using breast ultrasonography or MRI in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

Interventions for High Body Mass Index in Children and Adolescents: US Preventive Services Task Force Recommendation Statement.

Importance: Approximately 19.7% of children and adolescents aged 2 to 19 years in the US have a body mass index (BMI) at or above the 95th percentile for age and sex, based on Centers for Disease Control and Prevention growth charts from 2000. The prevalence of high BMI increases with age and is higher among Hispanic/Latino, Native American/Alaska Native, and non-Hispanic Black children and adolescents and children from lower-income families. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on interventions (behavioral counseling and pharmacotherapy) for weight loss or weight management in children and adolescents that can be provided in or referred from a primary care setting. Population: Children and adolescents 6 years or older. Evidence Assessment: The USPSTF concludes with moderate certainty that providing or referring children and adolescents 6 years or older with a high BMI to comprehensive, intensive behavioral interventions has a moderate net benefit. Recommendation: The USPSTF recommends that clinicians provide or refer children and adolescents 6 years or older with a high BMI (≥95th percentile for age and sex) to comprehensive, intensive behavioral interventions. (B recommendation).

Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy: US Preventive Services Task Force Recommendation Statement.

Importance: Iron deficiency is the leading cause of anemia during pregnancy. According to survey data from 1999 to 2006, overall estimated prevalence of iron deficiency during pregnancy is near 18% and increases across the 3 trimesters of pregnancy (from 6.9% to 14.3% to 28.4%). An estimated 5% of pregnant persons have iron deficiency anemia. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening and supplementation for iron deficiency with and without anemia on maternal and infant health outcomes in asymptomatic pregnant persons. Population: Asymptomatic pregnant adolescents and adults. Evidence Assessment: The USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. The USPSTF also concludes that the current evidence is insufficient, and the balance of benefits and harms of iron supplementation in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine supplementation for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement).

Interventions to Prevent Falls in Community-Dwelling Older Adults: US Preventive Services Task Force Recommendation Statement.

Importance: Falls are the leading cause of injury-related morbidity and mortality among older adults in the US. In 2018, 27.5% of community-dwelling adults 65 years or older reported at least 1 fall in the past year and 10.2% reported a fall-related injury. In 2021, an estimated 38 742 deaths resulted from fall-related injuries. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the effectiveness and harms of primary care-relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling adults 65 years or older. Population: Community-dwelling adults 65 years or older at increased risk of falls. Evidence Assessment: The USPSTF concludes with moderate certainty that exercise interventions provide a moderate net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. The USPSTF concludes with moderate certainty that multifactorial interventions provide a small net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. Recommendation: The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians individualize the decision to offer multifactorial interventions to prevent falls to community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient's values and preferences. (C recommendation).

Primary Care Interventions to Prevent Child Maltreatment: US Preventive Services Task Force Recommendation Statement.

Importance: Child maltreatment, which includes child abuse and neglect, can have profound effects on health, development, survival, and well-being throughout childhood and adulthood. The prevalence of child maltreatment in the US is uncertain and likely underestimated. In 2021, an estimated 600 000 children were identified by Child Protective Services as experiencing abuse or neglect and an estimated 1820 children died of abuse and neglect. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of primary care-feasible or referable behavioral counseling interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of maltreatment. Population: Children and adolescents younger than 18 years who do not have signs or symptoms of or known exposure to maltreatment. Evidence Assessment: The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of primary care interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of or known exposure to maltreatment. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement).

Association between exposure to specific PM2.5 constituents and environment, lifestyle, and clinical parameters in patients with COPD.

This study investigated the correlation between the individual chemical constituents of particulate matter 2.5 µm (PM2.5) and respiratory parameters as well as the living environment and daily behaviors in patients with chronic obstructive pulmonary disease (COPD). Data were obtained from prospective COPD panel conducted in South Korea. Following collection via a microPEM, 18 metallic elements were determined using energy-dispersive X-ray fluorescence spectroscopy. All participants completed detailed questionnaires on living environments and lifestyle practices. Eighty-nine stable COPD patients (mean age 68.1 years; 94.4% male) were analyzed. Several constituents (titanium, aluminum, bromine, and silicone) were significantly associated with respiratory outcomes. Copper and manganese concentrations were significantly associated with the living environment. Increased ventilation time and air purifier operation were associated with lower concentrations of copper, silicone, barium, and titanium. These findings suggest varying relationships between PM2.5 constituents and clinical parameters in COPD patients, providing a basis for personalized interventions and future research.

Gut microbiota composition and metabolite profiling in smokers: a comparative study between emphysema and asymptomatic individuals with therapeutic implications.

BACKGROUND: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema. METHODS: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation. RESULTS: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen. CONCLUSION: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.

Deep Learning-based Approach to Predict Pulmonary Function at Chest CT.

Background Low-dose chest CT screening is recommended for smokers with the potential for lung function abnormality, but its role in predicting lung function remains unclear. Purpose To develop a deep learning algorithm to predict pulmonary function with low-dose CT images in participants using health screening services. Materials and Methods In this retrospective study, participants underwent health screening with same-day low-dose CT and pulmonary function testing with spirometry at a university affiliated tertiary referral general hospital between January 2015 and December 2018. The data set was split into a development set (model training, validation, and internal test sets) and temporally independent test set according to first visit year. A convolutional neural network was trained to predict the forced expiratory volume in the first second of expiration (FEV1) and forced vital capacity (FVC) from low-dose CT. The mean absolute error and concordance correlation coefficient (CCC) were used to evaluate agreement between spirometry as the reference standard and deep-learning prediction as the index test. FVC and FEV1 percent predicted (hereafter, FVC% and FEV1%) values less than 80% and percent of FVC exhaled in first second (hereafter, FEV1/FVC) less than 70% were used to classify participants at high risk. Results A total of 16 148 participants were included (mean age, 55 years ± 10 [SD]; 10 981 men) and divided into a development set (n = 13 428) and temporally independent test set (n = 2720). In the temporally independent test set, the mean absolute error and CCC were 0.22 L and 0.94, respectively, for FVC and 0.22 L and 0.91 for FEV1. For the prediction of the respiratory high-risk group, FVC%, FEV1%, and FEV1/FVC had respective accuracies of 89.6% (2436 of 2720 participants; 95% CI: 88.4, 90.7), 85.9% (2337 of 2720 participants; 95% CI: 84.6, 87.2), and 90.2% (2453 of 2720 participants; 95% CI: 89.1, 91.3) in the same testing data set. The sensitivities were 61.6% (242 of 393 participants; 95% CI: 59.7, 63.4), 46.9% (226 of 482 participants; 95% CI: 45.0, 48.8), and 36.1% (91 of 252 participants; 95% CI: 34.3, 37.9), respectively. Conclusion A deep learning model applied to volumetric chest CT predicted pulmonary function with relatively good performance. © RSNA, 2023 Supplemental material is available for this article.

Effects of gastroesophageal reflux disease treatment with proton pump inhibitors on the risk of acute exacerbation and pneumonia in patients with COPD.

BACKGROUND: Gastroesophageal reflux disease (GERD) has been suggested as a risk factor for acute exacerbation of chronic obstructive pulmonary disease (COPD). However, it remains undetermined whether proton pump inhibitor (PPI) treatment reduces the risk of exacerbation or affects the risk of pneumonia. This study aimed to evaluate the risks of both exacerbation and pneumonia following PPI treatment for GERD in patients with COPD. METHODS: This study used a reimbursement database of the Republic of Korea. Patients aged ≥ 40 years with COPD as a main diagnosis and who received PPI treatment for GERD at least for 14 consecutive days between January 2013 and December 2018 were included in the study. A self-controlled case series analysis was conducted to calculate the risk of moderate and severe exacerbation and pneumonia. RESULTS: A total of 104,439 patients with prevalent COPD received PPI treatment for GERD. The risk of moderate exacerbation was significantly lower during the PPI treatment than at baseline. The risk of severe exacerbation increased during the PPI treatment but significantly decreased in the post-treatment period. Pneumonia risk was not significantly increased during the PPI treatment. The results were similar in patients with incident COPD. CONCLUSIONS: The risk of exacerbation was significantly reduced after PPI treatment compared with the non-treated period. Severe exacerbation may increase due to uncontrolled GERD but subsequently decrease following PPI treatment. There was no evidence of an increased risk of pneumonia.

External Validation of the eRADAR Risk Score for Detecting Undiagnosed Dementia in Two Real-World Healthcare Systems.

BACKGROUND: Fifty percent of people living with dementia are undiagnosed. The electronic health record (EHR) Risk of Alzheimer's and Dementia Assessment Rule (eRADAR) was developed to identify older adults at risk of having undiagnosed dementia using routinely collected clinical data. OBJECTIVE: To externally validate eRADAR in two real-world healthcare systems, including examining performance over time and by race/ethnicity. DESIGN: Retrospective cohort study PARTICIPANTS: 129,315 members of Kaiser Permanente Washington (KPWA), an integrated health system providing insurance coverage and medical care, and 13,444 primary care patients at University of California San Francisco Health (UCSF), an academic medical system, aged 65 years or older without prior EHR documentation of dementia diagnosis or medication. MAIN MEASURES: Performance of eRADAR scores, calculated annually from EHR data (including vital signs, diagnoses, medications, and utilization in the prior 2 years), for predicting EHR documentation of incident dementia diagnosis within 12 months. KEY RESULTS: A total of 7631 dementia diagnoses were observed at KPWA (11.1 per 1000 person-years) and 216 at UCSF (4.6 per 1000 person-years). The area under the curve was 0.84 (95% confidence interval: 0.84-0.85) at KPWA and 0.79 (0.76-0.82) at UCSF. Using the 90th percentile as the cut point for identifying high-risk patients, sensitivity was 54% (53-56%) at KPWA and 44% (38-51%) at UCSF. Performance was similar over time, including across the transition from International Classification of Diseases, version 9 (ICD-9) to ICD-10 codes, and across racial/ethnic groups (though small samples limited precision in some groups). CONCLUSIONS: eRADAR showed strong external validity for detecting undiagnosed dementia in two health systems with different patient populations and differential availability of external healthcare data for risk calculations. In this study, eRADAR demonstrated generalizability from a research sample to real-world clinical populations, transportability across health systems, robustness to temporal changes in healthcare, and similar performance across larger racial/ethnic groups.

Cancer-Related Dysfunctional Beliefs About Sleep Mediate the Influence of Sleep Disturbance on Fear of Progression Among Patients With Surgically Resected Lung Cancer.

BACKGROUND: Lung cancer is associated with significant psychological distress, including fear of progression (FoP). Because insomnia and depression are highly prevalent and associated with FoP, we examined the association between FoP, insomnia, and depression in cancer patients. Furthermore, we tested the mediation effect of cancer-related dysfunctional beliefs about sleep (C-DBS) on this association. METHODS: We analyzed data collected from patients with surgically resected non-small cell lung cancer from a single-center randomized controlled study investigating digital healthcare applications. Baseline demographic and clinical variables were collected. In addition, self-reported questionnaires including the Fear of Progression Questionnaire-Short Form, Patients Health Questionnaire-9 items (PHQ-9), Insomnia Severity Index, and C-DBS were administered. RESULTS: Among the 320 enrolled patients with lung cancer, a regression model showed that FoP was predicted by age (ß = -0.13, P = 0.007), PHQ-9 (ß = 0.35, P < 0.001), and C-DBS (ß = 0.28, P < 0.001). Insomnia did not directly influence FoP, but C-DBS mediated the association. Depression directly influenced FoP, but C-DBS did not mediate this association. CONCLUSION: Among patients with surgically resected lung cancer, C-DBS mediated the effects of severity of insomnia on FoP. Depression directly influenced FoP, but C-DBS did not influence this association. To reduce FoP among patients with lung cancer, C-DBS should be addressed in the cognitive behavioral therapy module.

Linear-Shaped Low-Bandgap Asymmetric Conjugated Donor Molecule for Fabrication of Bulk Heterojunction Small-Molecule Organic Solar Cells.

A linear-shaped small organic molecule (E)-4-(5-(3,5-dimethoxy-styryl)thiophen-2-yl)-7-(5″-hexyl-[2,2':5',2″-terthiophen]-5-yl)benzo[c][1,2,5]thiadiazole (MBTR) comprising a benzothiadiazole (BTD) acceptor linked with the terminal donors bithiophene and dimethoxy vinylbenzene through a π-bridge thiophene was synthesized and analyzed. The MBTR efficiently tuned the thermal, absorption, and emission characteristics to enhance the molecular packing and aggregation behaviors in the solid state. The obtained optical bandgap of 1.86 eV and low-lying highest occupied molecular orbital (HOMO) level of -5.42 eV efficiently lowered the energy losses in the fabricated devices, thereby achieving enhanced photovoltaic performances. The optimized MBTR:PC71BM (1:2.5 w/w%) fullerene-based devices showed a maximum power conversion efficiency (PCE) of 7.05%, with an open-circuit voltage (VOC) of 0.943 V, short-circuit current density (JSC) of 12.63 mA/cm2, and fill factor (FF) of 59.2%. With the addition of 3% 1,8-diiodooctane (DIO), the PCE improved to 8.76% with a high VOC of 1.02 V, JSC of 13.78 mA/cm2, and FF of 62.3%, which are associated with improved charge transport at the donor/acceptor interfaces owing to the fibrous active layer morphology and favorable phase separation. These results demonstrate that the introduction of suitable donor/acceptor groups in molecular design and device engineering is an effective approach to enhancing the photovoltaic performances of organic solar cells.

Attachment to Peers and School: Longitudinal Moderators of the Relation Between Caregiver Psychological Distress and Adolescent Hopelessness.

Research has yet to determine how relationships outside of the family system may buffer negative outcomes associated with hopelessness among racial minority youth. In a sample of Black American youth (N = 512; 49% females) and their parents or caregivers, this study used longitudinal growth models to explore whether youth relationships (attachment to peers and attachment to school) moderated the association between caregiver distress (depressive symptoms and traumatic stress), and youth hopelessness. Adolescents' gender was examined to determine if there were gender differences present in these associations. Four linear growth models showed a significant change in levels of hopelessness over time for youth and a significant positive relation between caregiver distress and youth level of hopelessness. Attachment to peers and attachment to school did not equally moderate the relation between caregiver psychological distress and youth hopelessness. The type of caregiver distress had a differential effect on youth hopelessness in the context of the moderation models and based on gender. The type of caregiver distress had a differential effect on youth hopelessness in the context of the moderation models and based on gender. Implications for the importance of non-familial attachments among Black American youth with distressed parents are discussed.

Immediate breast reconstruction has no impact on the oncologic outcomes of patients treated with post-mastectomy radiation therapy: a comparative analysis based on propensity score matching.

PURPOSE: To investigate the impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM). METHODS: After a retrospective review of patients treated with PMRT between 2008 and 2017, we included 153 patients who underwent iBR and 872 patients who did not undergo iBR. Among the 153 patients who underwent iBR, 34 received one-stage iBR with autologous tissue and 119 received two-stage iBR. Conventional fractionated PMRT with a total dose of 50-50.4 Gy in 25-28 fractions was performed in all patients. Propensity scores were calculated via logistic regression. RESULTS: Patients who underwent iBR were younger, had early stage disease, and had more frequent hormone receptor-positive tumor than those who did not undergo iBR. After PSM, 127 patients from each group with well-balanced characteristics were selected. With a median follow-up of 67.5 months, iBR led to better 6-year disease-free survival rates compared to no iBR before PSM (84.8% vs. 71.4%, p = 0.003); after PSM, there was no significant difference (84.8% vs. 75.5%, p = 0.130). On multivariable analysis in the matched cohort, iBR was not associated with inferior disease-free survival (hazard ratio, 0.67; p = 0.175). In the sensitivity analysis, iBR was not associated with a lower disease-free survival across all prognostic groups. The 5-year cumulative incidence of iBR failure was 15.0%. CONCLUSION: In patients with adverse pathologic factors planning to receive PMRT, iBR did not compromise oncologic outcomes. In addition, iBR can be considered in patients treated with PMRT with several clinicopathologic risk factors.

Comparing Machine Learning to Regression Methods for Mortality Prediction Using Veterans Affairs Electronic Health Record Clinical Data.

BACKGROUND: It is unclear whether machine learning methods yield more accurate electronic health record (EHR) prediction models compared with traditional regression methods. OBJECTIVE: The objective of this study was to compare machine learning and traditional regression models for 10-year mortality prediction using EHR data. DESIGN: This was a cohort study. SETTING: Veterans Affairs (VA) EHR data. PARTICIPANTS: Veterans age above 50 with a primary care visit in 2005, divided into separate training and testing cohorts (n= 124,360 each). MEASUREMENTS AND ANALYTIC METHODS: The primary outcome was 10-year all-cause mortality. We considered 924 potential predictors across a wide range of EHR data elements including demographics (3), vital signs (9), medication classes (399), disease diagnoses (293), laboratory results (71), and health care utilization (149). We compared discrimination (c-statistics), calibration metrics, and diagnostic test characteristics (sensitivity, specificity, and positive and negative predictive values) of machine learning and regression models. RESULTS: Our cohort mean age (SD) was 68.2 (10.5), 93.9% were male; 39.4% died within 10 years. Models yielded testing cohort c-statistics between 0.827 and 0.837. Utilizing all 924 predictors, the Gradient Boosting model yielded the highest c-statistic [0.837, 95% confidence interval (CI): 0.835-0.839]. The full (unselected) logistic regression model had the highest c-statistic of regression models (0.833, 95% CI: 0.830-0.835) but showed evidence of overfitting. The discrimination of the stepwise selection logistic model (101 predictors) was similar (0.832, 95% CI: 0.830-0.834) with minimal overfitting. All models were well-calibrated and had similar diagnostic test characteristics. LIMITATION: Our results should be confirmed in non-VA EHRs. CONCLUSION: The differences in c-statistic between the best machine learning model (924-predictor Gradient Boosting) and 101-predictor stepwise logistic models for 10-year mortality prediction were modest, suggesting stepwise regression methods continue to be a reasonable method for VA EHR mortality prediction model development.

Predicting Life Expectancy to Target Cancer Screening Using Electronic Health Record Clinical Data.

BACKGROUND: Guidelines recommend breast and colorectal cancer screening for older adults with a life expectancy >10 years. Most mortality indexes require clinician data entry, presenting a barrier for routine use in care. Electronic health records (EHR) are a rich clinical data source that could be used to create individualized life expectancy predictions to identify patients for cancer screening without data entry. OBJECTIVE: To develop and internally validate a life expectancy calculator from structured EHR data. DESIGN: Retrospective cohort study using national Veteran's Affairs (VA) EHR databases. PATIENTS: Veterans aged 50+ with a primary care visit during 2005. MAIN MEASURES: We assessed demographics, diseases, medications, laboratory results, healthcare utilization, and vital signs 1 year prior to the index visit. Mortality follow-up was complete through 2017. Using the development cohort (80% sample), we used LASSO Cox regression to select ~100 predictors from 913 EHR data elements. In the validation cohort (remaining 20% sample), we calculated the integrated area under the curve (iAUC) and evaluated calibration. KEY RESULTS: In 3,705,122 patients, the mean age was 68 years and the majority were male (97%) and white (85%); nearly half (49%) died. The life expectancy calculator included 93 predictors; age and gender most strongly contributed to discrimination; diseases also contributed significantly while vital signs were negligible. The iAUC was 0.816 (95% confidence interval, 0.815, 0.817) with good calibration. CONCLUSIONS: We developed a life expectancy calculator using VA EHR data with excellent discrimination and calibration. Automated life expectancy prediction using EHR data may improve guideline-concordant breast and colorectal cancer screening by identifying patients with a life expectancy >10 years.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.