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BACKGROUND: Electronic patient-reported outcome (ePRO) systems can be used to engage patients in remote symptom monitoring to support postoperative care. We interviewed thoracic surgery patients with ePRO experience to identify factors that influenced use of ePROs to report their symptoms post-discharge. METHOD: This qualitative study used semi-structured telephone interviews with adults who underwent major thoracic surgery at an academic medical center in North Carolina. Individuals who enrolled in symptom monitoring, completed at least one ePRO survey, and were reachable by phone for the interview were included. The ePRO surveys assessed 10 symptoms, including validated Patient-Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures and thoracic surgery-specific questions. Surveys, offered via web-based and automated telephone options, were administered for four weeks post-discharge with alerts sent to clinicians for concerning symptoms. The interviews were guided by the Capability, Opportunity, Motivation model for behavior change (COM-B) and examined factors that influenced patients' completion of ePRO surveys post-discharge. Team members independently coded interviews and identified themes, informed by COM-B. We report descriptive statistics (demographics, number of surveys completed) and themes organized by COM-B components. RESULTS: Of 28 patients invited, 25 (89%) completed interviews from July to October 2022. Participants were a median 58 years, 56% female, 80% White, and 56% had a history of malignancy. They completed 131/150 (87%) possible ePRO surveys. For capability, participants reported building ePROs into their routine and having the skills and knowledge, but lacking physical and emotional energy, to complete ePROs. For opportunity, participants identified the ease and convenience of accessing ePROs and providers' validation of ePROs. Motivators were perceived benefits of a deepening connection to their clinical team, improved symptom management for themselves and others, and self-reflection about their recovery. Factors limiting motivation included lack of clarity about the purpose of ePROs and a disconnect between symptom items and individual recovery experience. CONCLUSIONS: Patients described being motivated to complete ePROs when reinforced by clinicians and considered ePROs as valuable to their post-discharge experience. Future work should enhance ePRO patient education, improve provider alerts and communications about ePROs, and integrate options to capture patients' complex health journeys.
People who undergo thoracic surgery often experience pain and other symptoms while recovering at home. These symptoms can be severe and may reduce overall quality of life and potentially result in some patients returning to the hospital for future treatment. Electronic Patient-Reported Outcomes can be used as a method for having patients regularly track and report any symptoms they experience while at home, and how severe those symptoms are, using digital technology such as an online survey or automated phone survey. Surgical care team members may then follow up with patients about their symptoms. More information was needed about the patient experience with completing these surveys about their symptoms. In this study, we interviewed patients who had completed Electronic Patient-Reported Outcomes after thoracic surgery to understand what may (or may not) have impelled them to participate and to learn how to improve the use of these surveys for patients. This study found that patients generally felt they were able to complete the symptom surveys. Key motivators included feeling more connected to their surgeon by completing the symptom surveys and having the opportunity to reflect on how their recovery was going at home. However, patients also discussed not having a clear understanding of the purpose of the symptom surveys and how their responses might affect their care. The study findings highlight the need for improved patient education and indicate that improvements to the survey questions and to how surgeons review patients' responses may be needed.
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Motivación , Medición de Resultados Informados por el Paciente , Investigación Cualitativa , Procedimientos Quirúrgicos Torácicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos Quirúrgicos Torácicos/efectos adversos , Anciano , Calidad de Vida/psicología , Adulto , Encuestas y CuestionariosRESUMEN
Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET). Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling. Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017). Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.
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Antineoplásicos Hormonales , Neoplasias de la Mama , Cognición , Terapia por Ejercicio , Ejercicio Físico , Posmenopausia , Humanos , Femenino , Neoplasias de la Mama/psicología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Persona de Mediana Edad , Posmenopausia/psicología , Anciano , Terapia por Ejercicio/métodos , Antineoplásicos Hormonales/uso terapéutico , Memoria , Resultado del TratamientoRESUMEN
Little is known about how non-suicidal and suicidal self-injury are differentially genetically related to psychopathology and related measures. This research was conducted using the UK Biobank Resource, in participants of European ancestry (N = 2320 non-suicidal self-injury [NSSI] only; N = 2648 suicide attempt; 69.18% female). We compared polygenic scores (PGS) for psychopathology and other relevant measures within self-injuring individuals. Logistic regressions and likelihood ratio tests (LRT) were used to identify PGS that were differentially associated with these outcomes. In a multivariable model, PGS for anorexia nervosa (odds ratio [OR] = 1.07; 95% confidence intervals [CI] 1.01; 1.15) and suicidal behavior (OR = 1.06; 95% CI 1.00; 1.12) both differentiated between NSSI and suicide attempt, while the PGS for other phenotypes did not. The LRT between the multivariable and base models was significant (Chi square = 11.38, df = 2, p = 0.003), and the multivariable model explained a larger proportion of variance (Nagelkerke's pseudo-R2 = 0.028 vs. 0.025). While NSSI and suicidal behavior are similarly genetically related to a range of mental health and related outcomes, genetic liability to anorexia nervosa and suicidal behavior is higher among those reporting a suicide attempt than those reporting NSSI-only. Further elucidation of these distinctions is necessary, which will require a nuanced assessment of suicidal versus non-suicidal self-injury in large samples.
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Determining when DNA recovered from a crime scene transferred from its biological source, i.e., a sample's 'time-since-deposition' (TSD), can provide critical context for biological evidence. Yet, there remains no analytical techniques for TSD that are validated for forensic casework. In this study, we investigate whether morphological and autofluorescence measurements of forensically-relevant cell populations generated with Imaging Flow Cytometry (IFC) can be used to predict the TSD of 'touch' or trace biological samples. To this end, three different prediction frameworks for estimating the number of day(s) for TSD were evaluated: the elastic net, gradient boosting machines (GBM), and generalized linear mixed model (GLMM) LASSO. Additionally, we transformed these continuous predictions into a series of binary classifiers to evaluate the potential utility for forensic casework. Results showed that GBM and GLMM-LASSO showed the highest accuracy, with mean absolute error estimates in a hold-out test set of 29 and 21 days, respectively. Binary classifiers for these models correctly binned 94-96% and 98-99% of the age estimates as over/under 7 or 180 days, respectively. This suggests that predicted TSD using IFC measurements coupled to one or, possibly, a combination binary classification decision rules, may provide probative information for trace biological samples encountered during forensic casework.
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ADN , Medicina Legal , ADN/genética , Citometría de Flujo , Polimorfismo de Nucleótido SimpleRESUMEN
Background: Breast cancer and its treatment are associated with aberrant patterns of resting state functional connectivity (rsFC) between the hippocampus and several areas of the brain, which may account for poorer cognitive outcomes in patients. Higher cardiorespiratory fitness (CRF) has been associated with enhanced rsFC and cognitive performance; however, these associations have not been well studied in breast cancer. We examined the relationship between CRF, rsFC of the hippocampus, and cognitive performance among women newly diagnosed with breast cancer. Methods: Thirty-four postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (Mage = 63.59 ± 5.73) were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. During baseline assessments, participants completed functional brain imaging, a submaximal CRF test, and cognitive testing. Whole-brain, seed-based analyses were used to examine the relationship between CRF and hippocampal rsFC, with age, years of education, and framewise displacement included as covariates. Cognition was measured with a battery of validated neurocognitive measures, reduced to seven composite factors. Results: Higher CRF was positively associated with greater rsFC of the hippocampus to a cluster within the dorsomedial and dorsolateral frontal cortex (z-max = 4.37, p = 0.003, cluster extent = 1,020 voxels). Connectivity within cluster peaks was not significantly related to cognitive factors (all ps > 0.05). Discussion: CRF was positively associated with hippocampal rsFC to frontal cortex structures, comprising a network of regions commonly suppressed in breast cancer. Future longitudinal research is needed to explore whether baseline rsFC predicts long-term cognitive resilience in breast cancer.
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Alcohol use disorder (AUD) is moderately heritable with significant social and economic impact. Genome-wide association studies (GWAS) have identified common variants associated with AUD, however, rare variant investigations have yet to achieve well-powered sample sizes. In this study, we conducted an interval-based exome-wide analysis of the Alcohol Use Disorder Identification Test Problems subscale (AUDIT-P) using both machine learning (ML) predicted risk and empirical functional weights. This research has been conducted using the UK Biobank Resource (application number 30782.) Filtering the 200k exome release to unrelated individuals of European ancestry resulted in a sample of 147,386 individuals with 51,357 observed and 96,029 unmeasured but predicted AUDIT-P for exome analysis. Sequence Kernel Association Test (SKAT/SKAT-O) was used for rare variant (Minor Allele Frequency (MAF) < 0.01) interval analyses using default and empirical weights. Empirical weights were constructed using annotations found significant by stratified LD Score Regression analysis of predicted AUDIT-P GWAS, providing prior functional weights specific to AUDIT-P. Using only samples with observed AUDIT-P yielded no significantly associated intervals. In contrast, ADH1C and THRA gene intervals were significant (False discovery rate (FDR) <0.05) using default and empirical weights in the predicted AUDIT-P sample, with the most significant association found using predicted AUDIT-P and empirical weights in the ADH1C gene (SKAT-O P Default = 1.06 x 10 -9 and P Empirical weight = 6.25 x 10 -11 ). These findings provide evidence for rare variant association of the ADH1C gene with the AUDIT-P and highlight the successful leveraging of ML to increase effective sample size and prior empirical functional weights based on common variant GWAS data to refine and increase the statistical significance in underpowered phenotypes.
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Introduction: The availability of large-scale biobanks linking genetic data, rich phenotypes, and biological measures is a powerful opportunity for scientific discovery. However, real-world collections frequently have extensive missingness. While missing data prediction is possible, performance is significantly impaired by block-wise missingness inherent to many biobanks. Methods: To address this, we developed Missingness Adapted Group-wise Informed Clustered (MAGIC)-LASSO which performs hierarchical clustering of variables based on missingness followed by sequential Group LASSO within clusters. Variables are pre-filtered for missingness and balance between training and target sets with final models built using stepwise inclusion of features ranked by completeness. This research has been conducted using the UK Biobank (n > 500 k) to predict unmeasured Alcohol Use Disorders Identification Test (AUDIT) scores. Results: The phenotypic correlation between measured and predicted total score was 0.67 while genetic correlations between independent subjects was high >0.86. Discussion: Phenotypic and genetic correlations in real data application, as well as simulations, demonstrate the method has significant accuracy and utility for increasing power for genetic loci discovery.
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Analysis of DNA mixtures from sexual assault evidence is an ongoing challenge for DNA casework laboratories. To assist the forensic scientist address source and activity level propositions there is a significant need for new techniques that can provide information as to the source of DNA, particularly for sexual assault samples that do not involve semen. The goal of this study was to develop a new biological signature system that provides additional probative value to samples comprised of mixtures of epidermal and vaginal cells, as may be observed in cases involving digital penetration. Signatures were based on morphological and autofluorescence properties of individual cells collected through Imaging Flow Cytometry (IFC). Comparisons to reference cell populations from vaginal tissue and epidermal cells collected from hands showed strong multivariate differences across > 80 cellular measurements. These differences were used to build a predictive framework for classifying unknown cell populations as originating from epithelial cells associated with digital penetration or epidermal tissue. As part of the classification scheme, posterior probabilities of specific tissue group membership were calculated for each cell, along with multivariate similarity to that tissue type. We tested this approach on cell populations from reference tissue as well as mock casework samples involving hand swabbings following digital vaginal penetration. Many more cells classifying as non-epidermal tissue were detected in digital penetration hand swab samples than control hand swabbings. Minimum interpretation thresholds were developed to minimize false positives; these thresholds were also effective when screening licked hands, indicating the potential utility of this method for a variety of biological mixture types and depositional events relevant to forensic casework. Results showed that samples collected subsequent to digital penetration possessed markedly higher numbers of cells classifying as vaginal tissue as well as higher posterior probabilities for vaginal tissue (≥ 0.90) compared to cell populations collected from hands without prior contact with vaginal tissue. Additionally, digital penetration cell populations may be resolved from saliva cell populations and other non-target tissue types.
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Medicina Legal , Delitos Sexuales , Femenino , Humanos , Medicina Legal/métodos , ADN/análisis , Células Epidérmicas , Diferenciación CelularRESUMEN
Analysis of DNA mixtures from sexual assault evidence is an ongoing challenge for DNA casework laboratories. There is a significant need for new techniques that can provide information as to the source of DNA, particularly for sexual assault samples that do not involve semen. The goal of this study was to develop a new biological signature system that provides additional probative value to samples comprised of mixtures of epidermal and vaginal cells, as may be observed in cases involving digital penetration. Signatures were based on morphological and autofluorescence properties of individual cells collected through Imaging Flow Cytometry (IFC). Comparisons to reference cell populations from vaginal tissue and epidermal cells collected from hands showed strong multivariate differences across >80 cellular measurements. These differences were used to build a predictive framework for classifying unknown cell populations as originating from epithelial cells associated with digital penetration or epidermal tissue. As part of the classification scheme, posterior probabilities of specific tissue group membership were calculated for each cell, along with multivariate similarity to that tissue type. We tested this approach on cell populations from reference tissue as well as mock casework samples involving digital penetration. Many more cells classifying as non-epidermal tissue were detected in digital penetration samples than control hand swabbings. Minimum interpretation thresholds were developed to minimize false positives; these thresholds were also effective when screening licked hands, indicating the potential utility of this method for a variety of biological mixture types and depositional events relevant to forensic casework. Results showed that samples collected subsequent to digital penetration possessed markedly higher numbers of cells classifying as vaginal tissue as well as higher posterior probabilities for vaginal tissue (⥠0.90) compared to cell populations collected from hands without prior contact with vaginal tissue. Additionally, digital penetration cell populations may be resolved from saliva cell populations and other non-target tissue types.
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BACKGROUND: Non-suicidal self-injury and suicide attempt represent significant public health concerns. While these outcomes are related, there is prior evidence that their etiology does not entirely overlap. Efforts to directly differentiate risk across outcomes are uncommon, particularly among older, population-based cohorts. METHODS: This research has been conducted using the UK Biobank. Data on individuals' self-reported history of non-suicidal self-injury only versus suicide attempt (maximum N = 6643) were analyzed. Applying LASSO and standard logistic regression, participants reporting one of these outcomes were assessed for differences across a range of sociodemographic, behavioral, and environmental features. RESULTS: Sociodemographic features most strongly differentiated between the outcomes of non-suicidal self-injury only versus suicide attempt. Specifically, Black individuals were more likely to report a suicide attempt, as were those of mixed race, those endorsing higher levels of depressive symptoms or trauma history, and those who had experienced financial problems (odds ratios 1.02-3.92). Those more likely to engage in non-suicidal self-injury only were younger, female, had higher levels of education, those who resided with a partner, and those who had a recently injured relative. LIMITATIONS: Differences in timing across correlates and outcomes preclude the ability to establish causal pathways. CONCLUSIONS: The factors identified in the current study as differentially associated with non-suicidal self-injury only versus suicide attempt provide further evidence of at least partially distinct correlates, and warrant follow-up in independent samples to investigate causality.
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Conducta Autodestructiva , Factores Sociodemográficos , Intento de Suicidio , Humanos , Adulto , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/etiología , Conducta Autodestructiva/psicología , Intento de Suicidio/psicología , Intento de Suicidio/estadística & datos numéricos , Estudios de Cohortes , Reino Unido/epidemiología , Estatus Económico/estadística & datos numéricos , Escolaridad , Medición de Riesgo , Autoinforme , Modelos Logísticos , Masculino , Femenino , Oportunidad Relativa , Bases de Datos Factuales , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND: Variation in genes involved in ethanol metabolism has been shown to influence risk for alcohol dependence (AD) including protective loss of function alleles in ethanol metabolizing genes. We therefore hypothesized that people with severe AD would exhibit different patterns of rare functional variation in genes with strong prior evidence for influencing ethanol metabolism and response when compared to genes not meeting these criteria. OBJECTIVE: Leverage a novel case only design and Whole Exome Sequencing (WES) of severe AD cases from the island of Ireland to quantify differences in functional variation between genes associated with ethanol metabolism and/or response and their matched control genes. METHODS: First, three sets of ethanol related genes were identified including those a) involved in alcohol metabolism in humans b) showing altered expression in mouse brain after alcohol exposure, and altering ethanol behavioral responses in invertebrate models. These genes of interest (GOI) sets were matched to control gene sets using multivariate hierarchical clustering of gene-level summary features from gnomAD. Using WES data from 190 individuals with severe AD, GOI were compared to matched control genes using logistic regression to detect aggregate differences in abundance of loss of function, missense, and synonymous variants, respectively. RESULTS: Three non-independent sets of 10, 117, and 359 genes were queried against control gene sets of 139, 1522, and 3360 matched genes, respectively. Significant differences were not detected in the number of functional variants in the primary set of ethanol-metabolizing genes. In both the mouse expression and invertebrate sets, we observed an increased number of synonymous variants in GOI over matched control genes. Post-hoc simulations showed the estimated effects sizes observed are unlikely to be under-estimated. CONCLUSION: The proposed method demonstrates a computationally viable and statistically appropriate approach for genetic analysis of case-only data for hypothesized gene sets supported by empirical evidence.
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Alcoholismo , Humanos , Ratones , Animales , Alcoholismo/genética , Alcoholismo/diagnóstico , Exoma/genética , Alelos , Etanol , Mutación Silenciosa , Variación GenéticaRESUMEN
Objective: Alcohol consumption patterns during the COVID-19 pandemic have varied notably. Participants: We examined the acute impact of the pandemic on alcohol use disorder (AUD) in a generalizable sample of college students who were surveyed pre-pandemic and re-surveyed in May 2020. Method: Items assessed pre-pandemic included DSM-5 AUD and mental health symptoms. A COVID-19 impacts questionnaire was administered, and alcohol and mental health items re-assessed. Results: AUD symptoms decreased from pre-pandemic to during the pandemic, demonstrating a change in trajectory compared to prior cohorts. Students with persistent AUD reported greater concurrent symptoms of PTSD, depression, and alcohol consumption than those with remitted AUD (ps ≤ .02), but not increased COVID-19 impact. Persistent AUD status was predicted by higher sensation seeking and alcohol consumption. Conclusions: Students with concurrent mental health problems are at continued risk for persistent AUD. Findings highlight the impact of the college environment and social context for drinking on AUD.
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Genome-wide association studies (GWAS) have successfully identified common variants associated with BMI. However, the stability of aggregate genetic variation influencing BMI from midlife and beyond is unknown. By analysing 165,717 men and 193,073 women from the UKBiobank, we performed BMI GWAS on six independent five-year age intervals between 40 and 72 years. We then applied genomic structural equation modeling to test competing hypotheses regarding the stability of genetic effects for BMI. LDSR genetic correlations between BMI assessed between ages 40 to 73 were all very high and ranged 0.89 to 1.00. Genomic structural equation modeling revealed that molecular genetic variance in BMI at each age interval could not be explained by the accumulation of any age-specific genetic influences or autoregressive processes. Instead, a common set of stable genetic influences appears to underpin genome-wide variation in BMI from middle to early old age in men and women alike.
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Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Índice de Masa Corporal , Femenino , Genoma , Genómica , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Multiplex families have higher recurrence risk of schizophrenia compared to the families of sporadic cases, but the source of this increased recurrence risk is unknown. We used schizophrenia genome-wide association study data (N = 156,509) to construct polygenic risk scores (PRS) in 1005 individuals from 257 multiplex schizophrenia families, 2114 ancestry-matched sporadic cases, and 2205 population controls, to evaluate whether increased PRS can explain the higher recurrence risk of schizophrenia in multiplex families compared to ancestry-matched sporadic cases. Using mixed-effects logistic regression with family structure modeled as a random effect, we show that SCZ PRS in familial cases does not differ significantly from sporadic cases either with, or without family history (FH) of psychotic disorders (All sporadic cases p = 0.90, FH+ cases p = 0.88, FH- cases p = 0.82). These results indicate that increased burden of common schizophrenia risk variation as indexed by current SCZ PRS, is unlikely to account for the higher recurrence risk of schizophrenia in multiplex families. In the absence of elevated PRS, segregation of rare risk variation or environmental influences unique to the families may explain the increased familial recurrence risk. These findings also further validate a genetically influenced psychosis spectrum, as shown by a continuous increase of common SCZ risk variation burden from unaffected relatives to schizophrenia cases in multiplex families. Finally, these results suggest that common risk variation loading are unlikely to be predictive of schizophrenia recurrence risk in the families of index probands, and additional components of genetic risk must be identified and included in order to improve recurrence risk prediction.
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Trastornos Psicóticos , Esquizofrenia , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Herencia Multifactorial , Trastornos Psicóticos/genética , Factores de Riesgo , Esquizofrenia/epidemiología , Esquizofrenia/genéticaRESUMEN
Objective: Overweight and obesity [body mass index (BMI) ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity (rsFC) among women with breast cancer. Methods: The sample included 34 post-menopausal women newly diagnosed with Stage 0-IIa breast cancer (Mage = 63.59 ± 5.73) who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety. Results: Mean BMI was in the obese range (M = 31.83 ± 6.62). For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex (PFC), including ventrolateral PFC (vlPFC), dorsolateral PFC, and superior frontal gyrus (z range = 2.85-4.26). Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety (ß = 0.47, p < 0.01). Conclusion: Higher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted.
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BACKGROUND: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations. MATERIALS AND METHODS: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance. RESULTS: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents. CONCLUSION: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Adolescente , Negro o Afroamericano/genética , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudios Transversales , Metilación de ADN , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Madres , Proyectos Piloto , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
Physical activity may improve cognitive function in women with breast cancer. In a cross-sectional study, we explored the relationship between cognitive function and physical activity (actigraph) and cardiorespiratory fitness (sub-maximal graded exercise test) in 73 postmenopausal women with early stage breast cancer prior to the initiation of systemic adjuvant therapy. Cognitive function was assessed with a standardized battery of neurocognitive measures assessing eight domains. Data were analyzed using partial correlations, controlling for age and total hours of actigraph wear-time. Women were, on average, 63.71 (± 5.3) years of age with 15.47 (± 2.48) years of education. For physical activity, greater average number of steps per day were associated with better attention (r = .262, p = .032) and psychomotor speed (r = .301, p = .011); greater average hours of moderate and moderate/vigorous intensity physical activity were associated with better visual memory (r = .241, p = .049; r = .241, p = .049, respectively); and greater average daily energy expenditure was associated with better visual memory (r = .270, p = .027) and psychomotor speed (r = .292, p = .017). For fitness, higher peak maximum VO2 was associated with better concentration (r = .330, p = .006), verbal memory (r = .241, p = .048), and working memory (r = .281, p = .019). These results suggest that higher levels of physical activity and cardiorespiratory fitness are associated with better cognitive function in postmenopausal women with breast cancer. Randomized controlled trials (RCT) to examine whether physical activity improves cognitive function in women with breast cancer are warranted. These RCTs should also determine the mechanisms of the influence of physical activity on cognitive function. CLINICAL TRIALS REGISTRATION NUMBER: NCT02793921; Date: May 20, 2016.
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Neoplasias de la Mama/psicología , Capacidad Cardiovascular/fisiología , Cognición/fisiología , Ejercicio Físico/fisiología , Posmenopausia/fisiología , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Aptitud FísicaRESUMEN
OBJECTIVES: This study identified women with unique trajectories of executive function, concentration, and visual working memory before and during adjuvant therapy for breast cancer, and examined phenotypic and genotypic predictors associated with subgroups. SAMPLE & SETTING: 399 postmenopausal women, of whom 288 were women with early-stage breast cancer and 111 were women without breast cancer, matched on age and years of education to the women with breast cancer, and all at an urban cancer center. METHODS & VARIABLES: A repeated-measures design was used; assessments occurred before adjuvant therapy and every six months post-therapy initiation. Group-based trajectory modeling determined subgroups. Multinomial logistic regression identified phenotypic and genotypic characteristics. RESULTS: Three executive function and concentration trajectory subgroups were identified. IMPLICATIONS FOR NURSING: Advancing age, greater pretherapy fatigue, and poorer pretherapy cognitive function are associated with the low subgroups. DNA repair and oxidative stress mechanisms may be involved in the cognitive changes that women experience.
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Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Quimioterapia Adyuvante/efectos adversos , Trastornos del Conocimiento/psicología , Cognición/efectos de los fármacos , Adulto , Factores de Edad , Anciano , Anastrozol/efectos adversos , Anastrozol/uso terapéutico , Trastornos del Conocimiento/genética , Estudios de Cohortes , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Fenotipo , PosmenopausiaRESUMEN
INTRODUCTION: Atrial fibrillation (AF) is a common diagnosis of patients presenting to the emergency department (ED). Intravenous (IV) diltiazem bolus is often the initial drug of choice for acute management of AF with rapid ventricular response (RVR). The route of diltiazem after the initial IV loading dose may influence the disposition of the patient from the ED. However, no studies exist comparing oral (PO) immediate release and IV continuous infusion diltiazem in the emergency setting. The objective of this study was to compare the incidence of treatment failure, defined as a heart rate (HR) of >110 beats/min at four hours or conversion to another agent, between PO immediate release and IV continuous infusion diltiazem after an initial IV diltiazem loading dose in patients in AF with RVR. METHODS: This was a single-center, observational, retrospective study conducted at a tertiary academic medical center. The study population included patients ≥18 years old who presented to the ED in AF with a HR > 110 beats/min and received an initial IV diltiazem loading dose. We used multivariate logistic regression to assess the association between routes of administration and treatment failure. RESULTS: A total of 111 patients were included in this study. Twenty-seven percent (11/41) of the patients in the PO immediate-release group had treatment failure compared to 46% (32/70) in the IV continuous-infusion group. The unadjusted odds ratio (OR) of treatment failure with PO was less than IV at 0.4 (95% confidence interval [CI] [0.18, 0.99], p = 0.046). When we performed a multivariate analysis adjusted for race and initial HR, PO was still less likely to be associated with treatment failure than IV with an OR of 0.4 (95% CI [0.15, 0.94], p = 0.041). The median dose of PO diltiazem and IV continuous infusion diltiazem at four hours was 30 mg and 10 mg/h, respectively. CONCLUSION: After a loading dose of IV diltiazem, PO immediate-release diltiazem was associated with a lower rate of treatment failure at four hours than IV continuous infusion in patients with AF with RVR.
Asunto(s)
Administración Oral , Fibrilación Atrial/tratamiento farmacológico , Diltiazem/uso terapéutico , Frecuencia Cardíaca/fisiología , Infusiones Intravenosas/estadística & datos numéricos , Servicio de Urgencia en Hospital , Femenino , Humanos , Infusiones Intravenosas/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (nâ¯=â¯150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. TRIAL REGISTRATION: Clinicaltrials.govNCT02793921. Registered 20 May 2016.