Spatial PD-L1, immune-cell microenvironment, and genomic copy-number alteration patterns and drivers of invasive-disease transition in prospective oral precancer cohort.

BACKGROUND: Studies of the immune landscape led to breakthrough trials of programmed death-1 (PD-1) inhibitors for recurrent/metastatic head and neck squamous cell carcinoma therapy. This study investigated the timing, influence of somatic copy-number alterations (SCNAs), and clinical implications of PD-L1 and immune-cell patterns in oral precancer (OPC). METHODS: The authors evaluated spatial CD3, CD3/8, and CD68 density (cells/mm2 ) and PD-L1 (membranous expression in cytokeratin-positive intraepithelial neoplastic cells and CD68) patterns by multiplex immunofluorescence in a 188-patient prospective OPC cohort, characterized by clinical, histologic, and SCNA risk factors and protocol-specified primary end point of invasive cancer. The authors used Wilcoxon rank-sum and Fisher exact tests, linear mixed effect models, mediation, and Cox regression and recursive-partitioning analyses. RESULTS: Epithelial, but not CD68 immune-cell, PD-L1 expression was detected in 28% of OPCs, correlated with immune-cell infiltration, 9p21.3 loss of heterozygosity (LOH), and inferior oral cancer-free survival (OCFS), notably in OPCs with low CD3/8 cell density, dysplasia, and/or 9p21.3 LOH. High CD3/8 cell density in dysplastic lesions predicted better OCFS and eliminated the excess risk associated with prior oral cancer and dysplasia. PD-L1 and CD3/8 patterns revealed inferior OCFS in PD-L1 high intrinsic induction and dysplastic immune-cold subgroups. CONCLUSION: This report provides spatial insight into the immune landscape and drivers of OPCs, and a publicly available immunogenomic data set for future precancer interrogation. The data suggest that 9p21.3 LOH triggers an immune-hot inflammatory phenotype; whereas increased 9p deletion size encompassing CD274 at 9p24.1 may contribute to CD3/8 and PD-L1 depletion during invasive transition. The inferior OCFS in PD-L1-high, immune-cold OPCs support the development of T-cell recruitment strategies.

A semiparametric model for wearable sensor-based physical activity monitoring data with informative device wear.

Wearable sensors provide an exceptional opportunity in collecting real-time behavioral data in free living conditions. However, wearable sensor data from observational studies often suffer from information bias, since participants' willingness to wear the monitoring devices may be associated with the underlying behavior of interest. The aim of this study was to introduce a semiparametric statistical approach for modeling wearable sensor-based physical activity monitoring data with informative device wear. Our simulation study indicated that estimates from the generalized estimating equations showed ignorable bias when device wear patterns were independent of the participants physical activity process, but incrementally more biased when the patterns of device non-wear times were increasingly associated with the physical activity process. The estimates from the proposed semiparametric modeling approach were unbiased both when the device wear patterns were (i) independent or (ii) dependent to the underlying physical activity process. We demonstrate an application of this method using data from the 2003-2004 National Health and Nutrition Examination Survey ($N=4518$), to examine gender differences in physical activity measured using accelerometers. The semiparametric model can be implemented using our R package acc, free software developed for reading, processing, simulating, visualizing, and analyzing accelerometer data, publicly available at the Comprehensive R Archive Network.

An Ecological Momentary Assessment Study Investigating Self-efficacy and Outcome Expectancy as Mediators of Affective and Physiological Responses and Exercise Among Endometrial Cancer Survivors.

BACKGROUND: Previous studies have shown affective and physiological states in response to exercise as predictors of daily exercise, yet little is known about the mechanism underlying such effects. PURPOSE: To examine the mediating effects of self-efficacy and outcome expectancy on the relationships between affective and physiological responses to exercise and subsequent exercise levels in endometrial cancer survivors. METHODS: Ecological momentary assessment (EMA) surveys were delivered up to eight 5- to 7-day periods over 6 months. Participants (n = 100) rated their affective and physiological states before and after each exercise session (predictors) and recorded their self-efficacy and outcome expectancy each morning (mediators). Exercise (outcome) was based on self-reported EMA surveys and accelerometer measures. A 1-1-1 multilevel mediation model was used to disaggregate the within-subject (WS) and between-subject (BS) effects. RESULTS: At the WS level, a more positive affective state after exercise was associated with higher self-efficacy and positive outcome expectation the next day, which in turn was associated with higher subsequent exercise levels (ps < .05). At the BS level, participants who typically had more positive affective and experienced less intense physiological sensation after exercise had higher average self-efficacy, which was associated with higher average exercise levels (ps < .05). CONCLUSIONS: In endometrial cancer survivors, affective experience after exercise, daily self-efficacy and positive outcome expectation help explain the day-to-day differences in exercise levels within-person. Findings from this study highlight potentials for behavioral interventions that target affective experience after exercise and daily behavioral cognitions to promote physical activity in cancer survivors' everyday lives.

Feasibility and efficacy of a weight gain prevention intervention for breast cancer patients receiving neoadjuvant chemotherapy: a randomized controlled pilot study.

PURPOSE: Weight gain is common among breast cancer patients and may contribute to poorer treatment outcomes. Most programs target breast cancer survivors after the completion of therapy and focus on weight reduction. This study examined the feasibility and preliminary efficacy of an intervention designed to prevent primary weight gain among women receiving neoadjuvant chemotherapy for breast cancer. METHODS: Thirty-eight newly diagnosed stage II or III breast cancer patients were randomized to the BALANCE intervention or usual care within 3 weeks of starting neoadjuvant chemotherapy. The intervention used a size acceptance-based approach and encouraged home-based resistance and moderate-intensity aerobic exercise as well as a low energy-dense diet to prevent weight gain. Assessments were conducted at baseline, mid-chemotherapy (3 months), and post-chemotherapy (6 months). Intervention feasibility, acceptability, and preliminary effects on anthropometric, quality of life, and circulating biomarker measures were evaluated. RESULTS: Intervention participant retention (100%) and in-person session attendance (80%) were high during the intervention period, although attendance dropped to 43% for telephone-delivered sessions. The majority of participants reported being satisfied with the intervention during chemotherapy (88%). Participants in the intervention group had greater reductions in waist circumference (p = .03) and greater improvements in self-reported vitality scores (p = .03) than the control group at the end of chemotherapy. Significant effects on biomarkers were not observed. CONCLUSIONS: A size acceptance weight management program is feasible during neoadjuvant chemotherapy among breast cancer patients and may have beneficial effects on waist circumference and patient vitality. TRIAL REGISTRATION: This study was registered as a clinical trial at www.clinicaltrials.gov (NCT00533338).

Misclassification in Assessment of First Trimester In-utero Exposure to Drugs Used Proximally to Conception: the Example of Letrozole Utilization for Infertility Treatment.

Letrozole is an aromatase inhibitor that has an unapproved use for ovulation induction with infertility. Because of the proximity of this use to conception, we selected letrozole to study the effect of 3 different methods for identifying the pregnancy start date and their impact on exposure misclassification. Using electronic health data from the US Sentinel database (2001-2015), we identified live-birth pregnancies conceived through in-vitro fertilization or intrauterine insemination. The pregnancy start was calculated using 1) a validated algorithm to estimate the last menstrual period (LMP), 2) LMP + 14 days (i.e., conception estimate), and 3) the fertility-procedure date. We identified 47,628 live-births after intrauterine insemination (n = 24,962) and in-vitro fertilization (n = 22,666), in which 2,458 (5.3%) mothers received letrozole. The algorithm-based conception estimate occurred within 14 days of the fertility procedure for 78.3% of pregnancies. Defining pregnancy start as LMP (45.7/1,000 pregnancies) or LMP + 14 days (12.7/1,000 pregnancies) overestimated letrozole exposure during pregnancy by 8.4-fold and 2.3-fold, respectively, compared with defining it at the date of the fertility procedure (5.5/1,000 pregnancies). While most studies of drug utilization in pregnancy use LMP as the conventional pregnancy start, this introduced substantial exposure misclassification in the example of letrozole. LMP + 14 days was less biased. Researchers should carefully consider the impact of the method for identifying the pregnancy start date on the potential for exposure misclassification.

Change in physical activity and quality of life in endometrial cancer survivors receiving a physical activity intervention.

BACKGROUND: Endometrial cancer survivors are at an increased risk of poor quality of life outcomes. Physical activity is positively associated with general quality of life in this population, however, little is known about how changes in physical activity may be associated with changes in specific aspects of quality of life. The aim of this secondary data analysis was to explore the relationships between change in physical activity and change in physical, mental, social, and other aspects of quality of life in endometrial cancer survivors receiving a physical activity intervention. METHODS: Endometrial cancer survivors (N = 100) participated in a telephone-based physical activity intervention for six months. At baseline and post-intervention we measured physical activity via accelerometry and ecological momentary assessment, and quality of life via the Short Form Health Survey (SF-36), the Quality of Life of Adult Cancer Survivors instrument, the Brief Symptom Inventory, the Pittsburgh Sleep Quality Index, and the Perceived Stress Scale. We conducted structural equation modeling path analyses to investigate how physical activity post-intervention was associated with the quality of life measures' subscales post-intervention, adjusting for baseline levels and potentially confounding covariates. RESULTS: Increasing physical activity was positively associated with improvements in general health (p = .044), role limitation due to physical health (p = .005), pain (p = .041), and somatic distress (p = .023). There was no evidence to indicate that change in physical activity was associated with change in other aspects of quality of life. CONCLUSIONS: Endometrial cancer survivors are at higher risk for suffering from challenges to physical quality of life, and findings from this study suggest that increasing physical activity may alleviate some of these problems. Further research is needed to determine whether other aspects of quality of life are linked to change in physical activity. TRIAL REGISTRATION: Trial registration number: NCT00501761 Name of registry: clinicaltrials.gov Date of registration: July 16, 2007. Date of enrollment: June 16, 2005.

Endometrial cancer survivors' sleep patterns before and after a physical activity intervention: A retrospective cohort analysis.

OBJECTIVE: To identify the baseline sleep patterns of endometrial cancer survivors and examine the impact of a physical activity intervention on their sleep quality via retrospective secondary analysis. METHODS: Early-stage endometrial cancer survivors participated in a 6-month single-arm exercise intervention using printed materials, telephone-based counseling, and pedometers to encourage adherence to exercise guidelines. Participants completed questionnaires evaluating their sleep (PSQI), physical activity (CHAMPS), quality of life (SF-36), and stress (PSS) at baseline and study completion. RESULTS: Ninety-five survivors had PSQI data at both time points. Mean age was 57.1 years (range, 25-76). Mean body mass index was 34.3 kg/m2. The majority were non-Hispanic white (75%) and had stage I disease (80%). At baseline, most survivors (61%) had poor sleep quality (PSQI > 5), with 24% reporting fairly or very bad sleep. The majority (63%) slept <7 h/night. At least once during the preceding month, 83% had an episode of daytime dysfunction. A pairwise comparison showed that obese survivors had more sleep disturbances than normal weight survivors (p = 0.029). No other clinicodemographic factors were associated with sleep. In unadjusted analyses, sleep quality significantly improved in women who increased weekly total or moderate/vigorous physical activity (p = 0.004 and p < 0.050, respectively). This association persisted after adjusting for the potential covariates of age, time since diagnosis, obesity status, disease stage, and treatment (p = 0.026). CONCLUSIONS: Our data demonstrated that poor sleep is common and detrimental to endometrial cancer survivors. Increasing exercise may improve this dysfunction and should be investigated as part of a prospective study.

Predictors of enrollment in individual- and couple-based lifestyle intervention trials for cancer survivors.

PURPOSE: To utilize data from lifestyle intervention pilot studies for cancer survivors to elucidate demographic, disease-related, and health behavior factors that might predict enrollment in this type of research. Additionally, factors were differentially compared based on intervention design (i.e., individual versus couple-based). METHODS: Secondary data analysis was conducted regarding predictors of enrollment into lifestyle intervention studies, including Healthy Moves Weight Loss (individual participants, screened n = 89, enrolled n = 30) and Healthy Moves Couples (survivors and their partners, screened n = 197, enrolled n = 23). Due to small sample sizes, common in pilot studies, random forest analyses were used to maximize information yielded by the data. RESULTS: Results identified numerous important predictors of enrollment in individual and couple-based lifestyle interventions. Percent energy from fat and physical activity minutes were identified as important predictors for both recruitment methods. Age, cancer site, and marital status were important predictors of enrollment in the individual-based intervention. Weight, fiber consumption, and disease-related symptom severity and interference were important predictors of enrollment in the couple-based intervention. CONCLUSION: Although there was some overlap in predictors for enrollment between studies, many differential predictors were identified between individual versus couple-based study designs for lifestyle intervention in cancer survivors. Future lifestyle intervention studies for cancer survivors may benefit from targeting different predictors of enrollment based on study design to optimize recruitment. Additionally, understanding predictors may allow certain barriers to enrollment (i.e., symptom burden) to be directly addressed, making lifestyle intervention research more feasible and acceptable to difficult-to-recruit survivors.

Longitudinal social cognitive influences on physical activity and sedentary time in Hispanic breast cancer survivors.

OBJECTIVE: This study evaluated the effect of two home-based exercise interventions (one culturally adapted and one standard) on changes in social cognitive theory (SCT) variables, physical activity (PA), and sedentary time (ST), and determined the association between changes in SCT variables and changes in PA and ST in Hispanic breast cancer survivors. METHOD: Project VIVA! was a 16-week randomized controlled pilot study to test the effectiveness and feasibility of a culturally adapted exercise intervention for Mexican American and Puerto Rican breast cancer survivors in Houston, Texas and San Juan, Puerto Rico, respectively. Women (N = 89) completed questionnaires on SCT variables, PA, and ST and were then randomized to a 16-week culturally adapted exercise program, a non-culturally adapted standard exercise intervention or a wait-list control group. Multiple regression models were used to determine associations between changes in SCT variables and changes in PA and ST. RESULTS: Participants were in their late 50s (58.5 ± 9.2 years) and obese (31.0 ± 6.5 kg/m2 ). Women reported doing roughly 34.5 min/day of PA and spending over 11 h/day in sedentary activities. Across groups, women reported significant increases in exercise self-efficacy and moderate-intensity, vigorous-intensity, and total PA from baseline to follow-up (p < 0.05). Increased social support from family was associated with increases in vigorous-intensity PA. Increases in social modeling were associated with increases in moderate-intensity and total PA and with decreases in ST from baseline to follow-up (p < 0.05). CONCLUSIONS: Hispanic cancer survivors benefit from PA interventions that focus on increasing social support from family and friends and social modeling. Copyright © 2015 John Wiley & Sons, Ltd.

Health-related quality of life factors associated with completion of a study delivering lifestyle exercise intervention for endometrial cancer survivors.

PURPOSE: The aim of this study was to examine associations between participants' quality of life and study completion. This is a secondary analysis of an exercise intervention study for endometrial cancer survivors. METHODS: We considered data for one-hundred post-treatment endometrial cancer survivors from a single-arm, six-month longitudinal exercise study. Participants received a home-based intervention consisting of exercise recommendations and telephone counseling sessions to encourage adherence. In addition to monitoring adherence to physical exercise recommendations, participants completed multiple psychological assessments, including health-related quality of life. Associations between study completion and health-related quality of life factors were analyzed using generalized additive models, to allow for possibly nonlinear associations. RESULTS: Measures of bodily pain contributed to the odds of study completion in a nonlinear way (p = 0.025), suggesting that improvements in these factors were associated with study completion, especially for individuals reporting very high levels of pain. In addition, association between participants' levels of anxiety and study completion showed an inverse U-shaped relation: Whereas increase in anxiety was associated with higher odds of completion for individuals with low anxiety score (0-4), increase in anxiety contributed to lower odds of study completion for individuals with anxiety scores of approximately 5-10 (p = 0.035). CONCLUSIONS: Results from this study indicate that baseline health-related quality of life factors may be associated with study completion in exercise intervention studies. In order to increase study completion rates, individually tailored study strategies may be prepared based on the baseline quality of life responses.

Sexual health of endometrial cancer survivors before and after a physical activity intervention: A retrospective cohort analysis.

OBJECTIVE: Sexual dysfunction is common in endometrial cancer survivors (ECS). Our group previously tested a six-month exercise intervention in ECS. We performed a secondary analysis to determine intervention's impact on sexual health. METHODS: We studied 100 post-treatment Stage I-IIIa sedentary ECS who participated in a non-controlled, single-arm, home-based exercise intervention utilizing telephone counseling, printed material, and pedometers. Quality-of-life and physical activity measures were collected at baseline and six months. Sexual function (SF) and sexual interest (SI) scores were extracted from the QLACS questionnaire. RESULTS: Baseline SF and SI were lower in survivors with less than a four-year college degree (P<0.001). Baseline SI was higher in survivors who were married or living with a significant other (P=0.012). No significant differences in SF or SI were observed based on obesity status, race, time since diagnosis, or treatment type. Post-intervention, mean SF score improved (P=0.002), 51% of participants had improved SI, and 43% had improved SF. When controlled for age and time since diagnosis, a one-hour increase in weekly physical activity was associated with a 6.5% increased likelihood of improved SI (P=0.04). Increased physical activity was not associated with improved SF. CONCLUSIONS: Although causation cannot be determined in this study, the correlation between receipt of an exercise intervention and improved sexual health for ECS is a novel finding. This finding suggests a role for physical activity as a strategy to improve the sexual health of ECS, which our group is examining in a larger prospective study.

Trends in Incident Prescriptions for Behavioral Health Medications in the US, 2018-2022.

Importance: The COVID-19 pandemic reportedly increased behavioral health needs and impacted treatment access. Objective: To assess changes in incident prescriptions dispensed for medications commonly used to treat depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and opioid use disorder (OUD), before and during the COVID-19 pandemic. Design, Setting, and Participants: This was a cross-sectional study using comprehensive, population-level, nationally projected data from IQVIA National Prescription Audit on incident prescriptions (prescriptions dispensed to patients with no prior dispensing from the same drug class in the previous 12 months) dispensed for antidepressants, benzodiazepines, Schedule II (C-II) stimulants, nonstimulant medications for ADHD, and buprenorphine-containing medication for OUD (MOUD), from US outpatient pharmacies. Data were analyzed from April 2018 to March 2022. Exposure: Incident prescriptions by drug class (by prescriber specialty, patient age, and sex) and drug. Main Outcomes and Measures: Interrupted time-series analysis to compare changes in trends in the monthly incident prescriptions dispensed by drug class and percentage changes in aggregate incident prescriptions dispensed between April 2018 and March 2022. Results: Incident prescriptions dispensed for the 5 drug classes changed from 51 500 321 before the COVID-19 pandemic to 54 000 169 during the pandemic. The largest unadjusted percentage increase in incident prescriptions by prescriber specialty was among nurse practitioners across all drug classes ranging from 7% (from 1 811 376 to 1 944 852; benzodiazepines) to 78% (from 157 578 to 280 925; buprenorphine MOUD), whereas for patient age and sex, the largest increases were within C-II stimulants and nonstimulant ADHD drugs among patients aged 20 to 39 years (30% [from 1 887 017 to 2 455 706] and 81% [from 255 053 to 461 017], respectively) and female patients (25% [from 2 352 095 to 2 942 604] and 59% [from 395 678 to 630 678], respectively). Trends for C-II stimulants and nonstimulant ADHD drugs (slope change: 4007 prescriptions per month; 95% CI, 1592-6422 and 1120 prescriptions per month; 95% CI, 706-1533, respectively) significantly changed during the pandemic, exceeding prepandemic trends after an initial drop at the onset of the pandemic (level changes: -50 044 prescriptions; 95% CI, -80 202 to -19 886 and -12 876 prescriptions; 95% CI, -17 756 to -7996, respectively). Although buprenorphine MOUD dropped significantly (level change: -2915 prescriptions; 95% CI, -5513 to -318), trends did not significantly change for buprenorphine MOUD, antidepressants, or benzodiazepines. Conclusions and Relevance: Incident use of many behavioral health medications remained relatively stable during the COVID-19 pandemic in the US, whereas ADHD medications, notably C-II stimulants, sharply increased. Additional research is needed to differentiate increases due to unmet need vs overprescribing, highlighting the need for further ADHD guideline development to define treatment appropriateness.

acc: An R package to process, visualize, and analyze accelerometer data.

Wearable activity monitors are now widely used in behavioral and epidemiological studies to measure physical activity in free-living conditions. Despite the widespread use in research, the development of software to explore the data collected from these devices has been limited. We present acc, a comprehensive, free, and open-source R package to provide a seamless environment for exploring accelerometer data (https://cran.r-project.org/web/packages/acc). In this article, we demonstrate the software for processing, visualizing, and analyzing accelerometer data using real and simulated datasets.

BayesESS: A tool for quantifying the impact of parametric priors in Bayesian analysis.

Bayesian inference has become an attractive choice for scientists seeking to incorporate prior knowledge into their modeling framework. While the R community has been an important contributor in facilitating Bayesian statistical analyses, software to evaluate the impact of prior knowledge to such modeling framework has been lacking. In this article, we present BayesESS, a comprehensive, free, and open source R package for quantifying the impact of parametric priors in Bayesian analysis. We also introduce an accompanying web-based application for estimating and visualizing Bayesian effective sample size for purposes of conducting or planning Bayesian analyses.

Identifying COVID-19 cases and extracting patient reported symptoms from Reddit using natural language processing.

We used social media data from "covid19positive" subreddit, from 03/2020 to 03/2022 to identify COVID-19 cases and extract their reported symptoms automatically using natural language processing (NLP). We trained a Bidirectional Encoder Representations from Transformers classification model with chunking to identify COVID-19 cases; also, we developed a novel QuadArm model, which incorporates Question-answering, dual-corpus expansion, Adaptive rotation clustering, and mapping, to extract symptoms. Our classification model achieved a 91.2% accuracy for the early period (03/2020-05/2020) and was applied to the Delta (07/2021-09/2021) and Omicron (12/2021-03/2022) periods for case identification. We identified 310, 8794, and 12,094 COVID-positive authors in the three periods, respectively. The top five common symptoms extracted in the early period were coughing (57%), fever (55%), loss of sense of smell (41%), headache (40%), and sore throat (40%). During the Delta period, these symptoms remained as the top five symptoms with percent authors reporting symptoms reduced to half or fewer than the early period. During the Omicron period, loss of sense of smell was reported less while sore throat was reported more. Our study demonstrated that NLP can be used to identify COVID-19 cases accurately and extracted symptoms efficiently.

Effectiveness of a Home-Based Exercise Intervention in the Fitness Profile of Hispanic Survivors of Breast Cancer.

BACKGROUND: Home-based exercise interventions might be a desirable long-term option for breast cancer survivors to enhance compliance and long-term health benefits. PURPOSE: To assess the effectiveness of a home-based intervention aimed at helping survivors of breast cancer meet the physical activity guidelines of the American College of Sports Medicine. METHODS: Eighty-nine women (age: 55.4 ± 10 years; BMI: 31 ± 6.5 kg/m2) from two cancer centers serving Hispanic women participated in this study. Women performed a baseline assessment of cardiorespiratory fitness, muscle endurance and strength, flexibility, range of motion, and extremity disability. After baseline measures, women were randomized into a control (C) or exercise (E) group. The exercise intervention consisted of a walking program, elastic band strengthening, and flexibility exercises performed at home. The outcome measures were reassessed 16 weeks after baseline measures. RESULTS: The intervention showed a strong effect of time on muscle strength and shoulder range of motion, and time and group for self-reported disability. There were no differences in sedentary behavior, physical fitness, and disability measures across intervention groups, including both exercise groups combined and changes over time between intervention groups. CONCLUSION: It appears that a home-based intervention affects only upper body strength and related disability, indicating that other components might need closer monitoring for significant changes to occur across time.

Equivalent Pore Channel Model for Fluid Flow in Rock Based on Microscale X-ray CT Imaging.

Pore-scale modeling with a reconstructed rock microstructure has become a dominant technique for fluid flow characterization in rock thanks to technological improvements in X-ray computed tomography (CT) imaging. A new method for the construction of a pore channel model from micro-CT image analysis is suggested to improve computational efficiency by simplifying a highly complex pore structure. Ternary segmentation was applied through matching a pore volume experimentally measured by mercury intrusion porosimetry with a CT image voxel volume to distinguish regions denoted as "apparent" and "indistinct" pores. The developed pore channel model, with distinct domains of different pore phases, captures the pore shape dependence of flow in two dimensions and a tortuous flow path in three dimensions. All factors determining these geometric characteristics were identified by CT image analysis. Computation of an interaction flow regime with apparent and indistinct pore domains was conducted using both the Stokes and Brinkman equations. The coupling was successfully simulated and evaluated against the experimental results of permeability derived from Darcy's law. Reasonable agreement was found between the permeability derived from the pore channel model and that estimated experimentally. However, the model is still incapable of accurate flow modeling in very low-permeability rock. Direct numerical simulation in a computational domain with a complex pore space was also performed to compare its accuracy and efficiency with the pore channel model. Both schemes achieved reasonable results, but the pore channel model was more computationally efficient.

Characteristics Associated With U.S. Outpatient Opioid Analgesic Prescribing and Gabapentinoid Co-Prescribing.

INTRODUCTION: A considerable burden of prescription and illicit opioid-related mortality and morbidity in the U.S. is attributable to potentially unnecessary or excessive opioid prescribing, and co-prescribing gabapentinoids may increase risk of harm. Data are needed regarding physician and patient characteristics associated with opioid analgesic and opioid analgesic-gabapentinoid co-prescriptions to elucidate targets for reducing preventable harm. METHODS: Multiple logistic regression was utilized to examine patient and physician predictors of opioid analgesic prescriptions and opioid analgesic-gabapentinoid co-prescriptions in adult noncancer patients using the National Ambulatory Medical Care Survey 2015 public use data set. Potential predictors were selected based on literature review, clinical relevance, and random forest machine learning algorithms. RESULTS: Among the 11.8% (95% CI=9.8%, 13.9%) of medical encounters with an opioid prescription, 16.2% (95% CI=12.6%, 19.8%) had a gabapentinoid co-prescription. Among all gabapentinoid encounters, 40.7% (95% CI=32.6%, 48.7%) had an opioid co-prescription. Predictors of opioid prescription included arthritis (OR=1.87, 95% CI=1.30, 2.69). Predictors of new opioid prescription included physician status as an independent contractor (OR=3.67, 95% CI=1.38, 9.81) or part owner of the practice (OR=3.34, 95% CI=1.74, 6.42). Predictors of opioid-gabapentinoid co-prescription included patient age (peaking at age 55-64 years; OR=35.67, 95% CI=4.32, 294.43). CONCLUSIONS: Predictors of opioid analgesic prescriptions with and without gabapentinoid co-prescriptions were identified. These predictors can help inform and reinforce (e.g., educational) interventions seeking to reduce preventable harm, help identify populations for elucidating opioid-gabapentinoid risk-benefit profiles, and provide a baseline for evaluating subsequent public health measures.

Feasibility and Outcomes of an Exercise Intervention for Chemotherapy-Induced Heart Failure.

PURPOSE: Cancer treatment-related heart failure (HF) is an emerging health concern, as the number of survivors is increasing rapidly, and cardiac health issues are a leading cause of mortality in this population. While there is general evidence for the efficacy of exercise rehabilitation interventions, more research is needed on exercise rehabilitation interventions for patients specifically with treatment-induced HF and whether such interventions are safe and well-accepted. This study provides feasibility and health outcomes of a pilot exercise intervention for cancer survivors with chemotherapy-induced HF. METHODS: Twenty-five participants were randomized to a clinic-based exercise intervention or a wait-list control group or, alternatively, allowed to enroll in a home-based exercise intervention if they declined the randomized study. For purposes of analysis, both types of exercise programs were combined into a single intervention group. Repeated-measures analysis of variance was conducted to assess for significant time and treatment group main effects separately and time × treatment group interaction effects. RESULTS: Significant improvements in maximum oxygen uptake ((Equation is included in full-text article.)O2max) were observed in the intervention group. Intervention satisfaction and adherence were high for both clinic- and home-based interventions, with no reported serious adverse events. Enrollment was initially low for the clinic-based intervention, necessitating the addition of the home-based program as an intervention alternative. CONCLUSIONS: Results suggest that exercise rehabilitation interventions are feasible in terms of safety, retention, and satisfaction and have the potential to improve (Equation is included in full-text article.)O2max. To maximize adherence and benefits while minimizing participant burden, an ideal intervention may incorporate elements of both clinic-based supervised exercise sessions and a home-based program.

Identifying the dynamic gene regulatory network during latent HIV-1 reactivation using high-dimensional ordinary differential equations.

Reactivation of latently infected cells has emerged as an important strategy for eradication of HIV. However, genetic mechanisms of regulation after reactivation remain unclear. We describe a five-step pipeline to study the dynamics of the gene regulatory network following a viral reactivation using high-dimensional ordinary differential equations. Our pipeline implements a combination of five different methods, by detecting temporally differentially expressed genes (step 1), clustering genes with similar temporal expression patterns into a small number of response modules (step2), performing a functional enrichment analysis within each gene response module (step 3), identifying a network structure based on the gene response modules using ordinary differential equations (ODE) and a high-dimensional variable selection technique (step 4), and obtaining a gene regulatory model based on refined parameter estimates using nonlinear least squares (step 5). We applied our pipeline to a time course gene expression data of latently infected T-cells following a latency-reversion.