Browsing by Author "Shan, Mu"
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Item Bayesian Order Constrained Adaptive (BOCA) Design for Phase II Clinical Trials Evaluating Subgroup-Specific Treatment Effect(Sage, 2023) Shan, Mu; Guo, Beibei; Liu, Hao; Li, Qian; Zang, Yong; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthThe "one-size-fits-all'' paradigm is inappropriate for phase II clinical trials evaluating biotherapies, which are often expected to have substantial heterogeneous treatment effects among different subgroups defined by biomarker. For these biotherapies, the objective of phase II clinical trials is often to evaluate subgroup-specific treatment effects. In this article, we propose a simple yet efficient Bayesian adaptive phase II biomarker-guided design, referred to as the Bayesian-order constrained adaptive design, to detect the subgroup-specific treatment effects of biotherapies. The Bayesian order constrained adaptive design combines the features of the enrichment design and sequential design. It starts with a "all-comers" stage, and subsequently switches to an enrichment stage for either the marker-positive subgroup or marker-negative subgroup, depending on the interim analysis results. The go/no go enrichment criteria are determined by two posterior probabilities utilizing the inherent ordering constraint between two subgroups. We also extend the Bayesian-order constrained adaptive design to handle the missing biomarker situation. We conducted comprehensive computer simulation studies to investigate the operating characteristics of the Bayesian order constrained adaptive design, and compared it with other existing and conventional designs. The results shown that the Bayesian order constrained adaptive design yielded the best overall performance in detecting the subgroup-specific treatment effects by jointly considering the efficiency and cost-effectiveness of the trials. The software for simulation and trial implementation are available for free download.Item Evaluation of a “Meds-to-Beds” program on 30-day hospital readmissions(ACCP, 2020-05) Zillich, Alan J.; Jaynes, Heather A.; Davis, Hannah B.; Lantaff, Wendy M.; Myers, Jaclyn; Perkins, Susan M.; Shan, Mu; Snyder, Margie E.; Biostatistics, School of Public HealthBackground Effective programs for transitional care from hospital to home are needed to improve patient outcomes. Purpose To evaluate readmissions among patients who received a medication discharge program compared with control patients who did not receive the program. Methods This was a retrospective, observational cohort study during a 1-year period in a medium-sized Midwestern health system. The “meds-to-beds” program consisted of a pharmacist and/or technician delivering patient's medications to bedside prior to discharge. When indicated, the pharmacist provided medication counseling, reviewed discharge medications, and provided an updated medication list to patients. The intervention cohort was defined as all hospitalized patients eligible for and opting into the “meds-to-beds” program. The control cohort was defined as hospitalized patients eligible for the program who did not opt-in to receive it. Data were collected through both a retrospective chart review and an administrative claims data warehouse. The primary outcome was defined as any 30-day readmissions. Secondary outcomes were defined as any preventable 30-day readmissions using the Agency for Healthcare Research and Quality's potentially avoidable hospitalization for ambulatory care sensitive conditions classification. Multivariable logistic regression models examined the odds of 30-day readmissions between the intervention and control groups. Results Data were collected for 500 intervention and 1591 control patients. Both groups were similar with respect to age, gender, race, co-morbid conditions, and previous health care utilization. In the multivariable model, all-cause readmissions within 30 days were not significantly different between the intervention and control groups (odds ratio [OR] = 0.67; 95% confidence interval [CI]: 0.42-1.07, P = .09). The most common preventable readmissions were for pneumonia (43.2%), heart failure (18.9%), and dehydration (16.2%). In the multivariable model, patients in the intervention group were less likely to be readmitted for a preventable cause within 30-days than patients in the control group (OR = 0.49; 95% CI: 0.28-0.89, P = .02). Conclusion This “meds-to-beds” program was not associated with a significant reduction in 30-day all-cause readmissions but was associated with a reduction in 30-day preventable hospital readmissions.Item Feasibility and acceptability of an acceptance and commitment therapy intervention for caregivers of adults with Alzheimer’s disease and related dementias(BMC, 2021-02-16) Fowler, Nicole R.; Judge, Katherine S.; Lucas, Kaitlyn; Gowan, Tayler; Stutz, Patrick; Shan, Mu; Wilhelm, Laura; Parry, Tommy; Johns, Shelley A.; Medicine, School of MedicineBackground: Caregivers of patients with Alzheimer's disease or a related dementia (ADRD) report high levels of distress, including symptoms of anxiety and depression, caregiving burden, and existential suffering; however, those with support and healthy coping strategies have less stress and burden. Acceptance and Commitment Therapy (ACT) aims to foster greater acceptance of internal events while promoting actions aligned with personal values to increase psychological flexibility in the face of challenges. The objective of this single-arm pilot, Telephone Acceptance and Commitment Therapy Intervention for Caregivers (TACTICs), was to evaluate the feasibility, acceptability, and preliminary effects of an ACT intervention on ADRD caregiver anxiety, depressive symptoms, burden, caregiver suffering, and psychological flexibility. Methods: ADRD caregivers ≥21 years of age with a Generalized Anxiety Disorder Scale (GAD-7) score ≥ 10 indicative of moderate or higher symptoms of anxiety were enrolled (N = 15). Participants received a telephone-based ACT intervention delivered by a non-licensed, bachelor's-prepared trained interventionist over 6 weekly 1-h sessions that included engaging experiential exercises and metaphors designed to increase psychological flexibility. The following outcome measures were administered at baseline (T1), immediately post-intervention (T2), 3 months post-intervention (T3), and 6 months post-intervention (T4): anxiety symptoms (GAD-7; primary outcome); secondary outcomes of depressive symptoms (Patient Health Questionnaire-9), burden (Zarit Burden Interview), suffering (The Experience of Suffering measure), psychological flexibility/experiential avoidance (Acceptance and Action Questionnaire-II), and coping skills (Brief COPE). Results: All 15 participants completed the study and 93.3% rated their overall satisfaction with their TACTICs experience as "completely satisfied." At T2, caregivers showed large reduction in anxiety symptoms (SRM 1.42, 95% CI [0.87, 1.97], p < 0.001) that were maintained at T3 and T4. At T4, psychological suffering (SRM 0.99, 95% CI [0.41, 1.56], p = 0.0027) and caregiver burden (SRM 0.79, 95% CI [0.21, 1.37], p = 0.0113) also decreased. Conclusions: Despite a small sample size, the 6-session manualized TACTICs program was effective in reducing anxiety, suggesting that non-clinically trained staff may be able to provide an effective therapeutic intervention by phone to maximize intervention scalability and reach.Item Patient characteristics and clinical factors affecting lumpectomy cavity volume: implications for partial breast irradiation(Frontiers Media, 2023-05-23) Le, Amy; Achiko, Flora Amy; Boyd, LaKeisha; Shan, Mu; Zellars, Richard C.; Rhome, Ryan M.; Radiation Oncology, School of MedicineIntroduction: Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)-based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes. Methods: A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors. Results: Median age was 61.0 years (range, 30-91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume. Discussion: These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses.Item The Relationship Between Family Caregivers’ Anticipatory Grief and Severity of Dementia(Oxford University Press, 2021-12-17) Gavin, Nicole; Shan, Mu; Johns, Shelly; Judge, Katherine; Fowler, Nicole; Medicine, School of MedicineAnticipatory grief is the process of experiencing normal bereavement before the physical death of a significant person. To date, anticipatory grief has been related to higher levels of caregiver depression, anxiety, subjective burden, and poorer problem solving. Additionally, higher levels anticipatory grief are observed in caregivers of those with Alzheimer’s Disease and Related Dementias (ADRD) compared to caregivers of those with mild cognitive impairment, implying a relationship between disease severity and caregiver anticipatory grief. Analyses were performed on data for ADRD caregivers (n=56) enrolled in the IU Telephone Acceptance and Commitment Therapy for Caregiver (TACTICs) trial; an RCT evaluating an ACT intervention for ADRD caregivers with anxiety. Inclusion criteria included identifying as the primary caregiver of an ADRD patient, and clinically significant anxiety (GAD7 score >10). The average age of caregivers was 61.9 years, 41.1% were spouses, 83.9% were white and 14.3% were black. Mean anticipatory grief scores were notably higher (84.6) compared to the previously reported means across the literature (74.9). Using multiple regression models, we determined a caregivers’ anticipatory grief, as measured by the anticipatory grief scale, is not significantly associated with the patients’ dementia severity, as measured by the Dementia Severity Rating Scale (DSRS) (p=0.66), Results revealed that higher levels of caregiver burden, as measured by the Zarit Burden Index, are significantly associated with more anticipatory grief (p< 0.01). Understanding these relationships contributes to a better understanding of ADRD caregivers, identifying “high-risk” caregivers, and informing future interventions and care.Item Transcriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis(Wolters Kluwer, 2022) Yang, Zhihong; Han, Sen; Zhang, Ting; Kusumanchi, Praveen; Huda, Nazmul; Tyler, Kelsey; Chandler, Kristina; Skill, Nicholas J.; Tu, Wanzhu; Shan, Mu; Jiang, Yanchao; Maiers, Jessica L.; Perez, Kristina; Ma, Jing; Liangpunsakul, Suthat; Medicine, School of MedicineAlcohol-associated liver disease is the leading cause of chronic liver disease. We hypothesized that the expression of specific coding genes is critical for the progression of alcoholic cirrhosis (AC) from compensated to decompensated states. For the discovery phase, we performed RNA sequencing analysis of 16 peripheral blood RNA samples, 4 healthy controls (HCs) and 12 patients with AC. The DEGs from the discovery cohort were validated by quantitative polymerase chain reaction in a separate cohort of 17 HCs and 48 patients with AC (17 Child-Pugh A, 16 Child-Pugh B, and 15 Child-Pugh C). We observed that the numbers of differentially expressed messenger RNAs (mRNAs) were more pronounced with worsening disease severity. Pathway analysis for differentially expressed genes for patients with Child-Pugh A demonstrated genes involved innate immune responses; those in Child-Pugh B belonged to genes related to oxidation and alternative splicing; those in Child-Pugh C related to methylation, acetylation, and alternative splicing. We found significant differences in the expression of heme oxygenase 1 (HMOX1) and ribonucleoprotein, PTB binding 1 (RAVER1) in peripheral blood of those who died during the follow-up when compared to those who survived. Conclusion: Unique mRNAs that may implicate disease progression in patients with AC were identified by using a transcriptomic approach. Future studies to confirm our results are needed, and comprehensive mechanistic studies on the implications of these genes in AC pathogenesis and progression should be further explored.