Publications by authors named "Brian L Egleston"

138 Publications

A Pilot Study of a Collaborative Palliative and Oncology Care Intervention for Patients with Head and Neck Cancer.

J Palliat Med 2021 Apr 13. Epub 2021 Apr 13.

Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

Palliative care improves symptoms and coping in patients with advanced cancers, but has not been evaluated for patients with curable solid malignancies. Because of the tremendous symptom burden and high rates of psychological distress in head and neck cancer (HNC), we evaluated feasibility and acceptability of a palliative care intervention in patients with HNC receiving curative-intent chemoradiation therapy (CRT). This was a prospective single-arm study in HNC patients receiving CRT at a single center in the United States. The intervention entailed weekly palliative care visits integrated with oncology care with a focus on symptoms and coping. The primary outcome was feasibility, defined as a >50% enrollment rate with >70% of patients attending at least half of the visits. To assess acceptability, we collected satisfaction ratings post-intervention. We also explored symptom burden, mood, and quality of life (QOL). We enrolled 91% (20/22) of eligible patients. Patients attended 133 of 138 palliative care visits (96%); all 20 attended >85% of visits. Eighteen of 19 (95%) found the intervention "very helpful" and would "definitely recommend" it. QOL and symptom burden worsened from baseline to week 5, but subsequently improved at one-month post-CRT. Overall, patients valued the one-on-one format of the intervention and receipt of additional care. Our palliative care intervention during highly morbid CRT was feasible and acceptable with high enrollment, excellent intervention compliance, and high patient satisfaction. Future randomized studies will further explore the impact on patient-reported outcomes and health care utilization.
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http://dx.doi.org/10.1089/jpm.2020.0656DOI Listing
April 2021

The usefulness of the Electronic Patient Visit Assessment (ePVA) as a clinical support tool for real-time interventions in head and neck cancer.

Mhealth 2021 20;7. Epub 2021 Jan 20.

Fox Chase Cancer Center, Philadelphia, PA, USA.

Background: Patients with head and neck cancer (HNC) experience painful, debilitating symptoms and functional limitations that can interrupt cancer treatment, and decrease their health-related quality of life (HRQoL). The Electronic Patient Visit Assessment (ePVA) for head and neck is a web-based mHealth patient-reported measure that asks questions about 21 categories of symptoms and functional limitations common to HNC. This article presents the development and usefulness of the ePVA as a clinical support tool for real-time interventions for patient-reported symptoms and functional limitations in HNC.

Methods: Between January 2018 and August 2019, 75 participants were enrolled in a clinical usefulness study of the ePVA. Upon signing informed consent, participants completed the ePVA and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) general (C30) questionnaire v3.0 (scores range from 0 to 100 with 100 representing best HRQoL). Clinical usefulness of the ePVA was defined as demonstration of reliability, convergent validity with HRQoL, and acceptability of the ePVA (i.e., >70% of eligible participants complete the ePVA at two or more visits and >70% of ePVA reports are read by providers). Formal focus group discussions with the interdisciplinary team that cared for patients with HNC guided the development of the ePVA as a clinical support tool. Qualitative and quantitative methods were used throughout the study. Descriptive statistics consisting of means and frequencies, Pearson correlation coefficient, and Student's t-tests were calculated using SAS 9.4 and STATA.

Results: The participants were primarily male (71%), White (76%), diagnosed with oropharyngeal or oral cavity cancers (53%), and undergoing treatment for HNC (69%). Data analyses supported the reliability (alpha =0.85), convergent validity with HRQoL scores, and acceptability of the ePVA. Participants with the highest number of symptoms and functional limitations reported significantly worse HRQoL (sum of symptoms: r=-0.50, P<0.0001; sum of function limitations: r=-0.56, P<0.0001). Ninety-two percent of participants (59 of 64) who had follow-up visits within the 6-month study period completed the ePVA at two or more visits and providers read 89% (169 of 189) of automated ePVA reports. The use of the ePVA as a clinical support tool for real-time interventions for symptoms and functional limitations reported by patients is described in a clinical exemplar.

Conclusions: This research indicates that the ePVA may be a useful mHealth tool as a clinical support tool for real-time interventions for patient-reported symptoms and functional limitations in HNC. The study findings support future translational research to enhance the usefulness of the ePVA in real world settings for early interventions that decrease symptom burden and improve the QoL of patients with HNC.
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http://dx.doi.org/10.21037/mhealth-19-250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882269PMC
January 2021

Patient-reported Quality of Life After SBRT, LDR, and HDR Brachytherapy for Prostate Cancer: A Comparison of Outcomes.

Am J Clin Oncol 2021 04;44(4):131-136

Departments of Radiation Oncology.

Purpose: We sought to compare changes in patient-reported quality of life (PRQOL) following stereotactic body radiation therapy (SBRT), high dose rate (HDR), and low dose rate (LDR) brachytherapy for prostate cancer.

Materials And Methods: International Prostate Symptom Score (IPSS), Sexual Health Inventory For Men (SHIM), and Expanded Prostate cancer Index Composite Short Form (EPIC-26) were prospectively collected for men with low/intermediate-risk cancer treated at a single institution. We used Generalized Estimating Equations to identify associations between variables and early (3 to 6 mo) or late (1 to 2 y) PRQOL scores. Minimally important differences (MID) were compared with assess clinical relevance.

Results: A total of 342 LDR, 159 HDR, and 112 SBRT patients treated from 2001 to 2018 were eligible. Gleason score, PSA, and age were lower among LDR patients compared with HDR/SBRT. Unadjusted baseline IPSS score was similar among all groups. Adjusted IPSS worsened at all time points compared with baseline after LDR/HDR. At early/late time points, rates of IPSS MID after LDR were higher compared to HDR/SBRT. There were no IPSS differences between SBRT and HDR. All modalities showed early and late SHIM worsening. There were no temporal differences in SHIM between SBRT and brachytherapy. There were no differences in EPIC subdomains between HDR and SBRT. Bowel symptoms worsened early after SBRT, whereas urinary irritative/obstructive symptoms worsened late after HDR. Among all domains, MID after SBRT and HDR were similar.

Conclusions: In a cohort of patients treated with modern radiotherapy techniques, HDR and SBRT resulted in clinically meaningful improved urinary PRQOL compared with LDR.
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http://dx.doi.org/10.1097/COC.0000000000000796DOI Listing
April 2021

Early postoperative outcomes in implant, pedicled, and free flap reconstruction for breast cancer: an analysis of 23,834 patients from the ACS-NSQIP datasets.

Breast Cancer Res Treat 2021 Jan 19. Epub 2021 Jan 19.

Department of Surgery, Einstein Healthcare Network, 5501 Old York Rd, Philadelphia, PA, 19141, USA.

Introduction: Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing implant, free flap, and pedicled flap reconstruction.

Methods: Patients undergoing implant, pedicled flap, and free flap reconstruction were identified in the 2011-2016 NSQIP database. Demographics were analyzed and covariates were balanced using overlap propensity score. Logistic regression was used for binary outcomes and Gamma GLM for length of stay (LOS).

Results: Of 23,834 patients, 87.7% underwent implant, 8.1% free flap, and 4.2% pedicled flap reconstruction. The implant group had the lowest mean operative time (206 min, SD 85.6). Implant patients had less pneumonia (OR 0.09, CI 0.02-0.36, p < 0.01), return to operating room (OR 0.62, CI 0.50-0.75, p < 0.01), venous thromboembolism (VTE) (OR 0.33, CI 0.14-0.79, p = 0.01), postoperative bleeding (OR 0.10, CI 0.06-0.15, p < 0.01), and urinary tract infections (UTI) (OR 0.21, CI 0.07-0.58, p < 0.01) than free flap patients. Pedicled flap patients had less postoperative bleeding (OR 0.69, CI 0.49-0.96, p = 0.03) than free flap patients. Pedicled flap patients had more superficial surgical site infections (p = 0.03), pneumonia (p = 0.02), postoperative bleeding (p < 0.01), VTE (p = 0.04), sepsis (p = 0.05), and unplanned reintubation (p = 0.01) than implant patients. Implant patients had the lowest LOS (1.6 days, p < 0.01).

Conclusion: Implant reconstruction has less short-term postoperative complications than free flaps and pedicled flap reconstructions. The overall complication rate among all reconstructive modalities remains acceptably low and patients should be informed of all surgical options.
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http://dx.doi.org/10.1007/s10549-020-06073-8DOI Listing
January 2021

Development of a Web-Based Supportive Care Program for Patients With Head and Neck Cancer.

Front Oncol 2020 15;10:602202. Epub 2020 Dec 15.

Triad Interactive Inc., Washington, DC, United States.

Patients undergoing radiation treatment for head and neck cancer experience significant side-effects that can impact a wide range of daily activities. Patients often report receiving insufficient information during and after treatment, which could impede rehabilitation efforts; they may also encounter practical and logistical barriers to receipt of supportive care. Thus, we developed a web-based program, , to provide information and strategies for managing symptom-focused concerns, which may be easily accessed from the patient's home. The purpose of this study was to evaluate patient acceptability and satisfaction with the program. In Phase 1, five patients with head and neck squamous cell carcinoma (HNSCC) reviewed the web-based program and provided initial feedback, which informed program modifications. In Phase 2, 55 patients were recruited to evaluate the program. Patient assessments were obtained prior to and after use of the web-based program, and included measures of psychological distress, self-efficacy in coping with cancer-related issues, and satisfaction with the website. Among the 55 patients enrolled, 44 logged in and viewed the web-based program. Participants reported high levels of satisfaction with the information received, and indicated that the website was interesting and easy to use. Older age and higher levels of self-efficacy in coping were each associated with higher levels of satisfaction with the website. In summary, the web-based program was well-received by patients, the majority of whom found it to be informative and useful. An easy-to-use web-based program, particularly for older patients who may have difficulty locating reliable evidence-based information on the internet, may be helpful in addressing survivors' needs in symptom management and coping with cancer.

Clinical Trial Registration: https://clinicaltrials.gov/, NCT02442336.
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http://dx.doi.org/10.3389/fonc.2020.602202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771721PMC
December 2020

Website Terms of Use May Limit Research about Online Physician Reviews.

Ann Vasc Surg 2021 Jan 3;70:e7. Epub 2020 Sep 3.

Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA.

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http://dx.doi.org/10.1016/j.avsg.2020.08.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744426PMC
January 2021

Statistical inference for natural language processing algorithms with a demonstration using type 2 diabetes prediction from electronic health record notes.

Biometrics 2020 Jul 22. Epub 2020 Jul 22.

Department of Computer and Information Sciences, Temple University, Philadelphia, PA.

The pointwise mutual information statistic (PMI), which measures how often two words occur together in a document corpus, is a cornerstone of recently proposed popular natural language processing algorithms such as word2vec. PMI and word2vec reveal semantic relationships between words and can be helpful in a range of applications such as document indexing, topic analysis, or document categorization. We use probability theory to demonstrate the relationship between PMI and word2vec. We use the theoretical results to demonstrate how the PMI can be modeled and estimated in a simple and straight forward manner. We further describe how one can obtain standard error estimates that account for within-patient clustering that arises from patterns of repeated words within a patient's health record due to a unique health history. We then demonstrate the usefulness of PMI on the problem of predictive identification of disease from free text notes of electronic health records. Specifically, we use our methods to distinguish those with and without type 2 diabetes mellitus in electronic health record free text data using over 400 000 clinical notes from an academic medical center.
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http://dx.doi.org/10.1111/biom.13338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854976PMC
July 2020

Longitudinal follow-up after telephone disclosure in the randomized COGENT study.

Genet Med 2020 08 7;22(8):1401-1406. Epub 2020 May 7.

Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: To better understand the longitudinal risks and benefits of telephone disclosure of genetic test results in the era of multigene panel testing.

Methods: Adults who were proceeding with germline cancer genetic testing were randomized to telephone disclosure (TD) with a genetic counselor or in-person disclosure (IPD) (i.e., usual care) of test results. All participants who received TD were recommended to return to meet with a physician to discuss medical management recommendations.

Results: Four hundred seventy-three participants were randomized to TD and 497 to IPD. There were no differences between arms for any cognitive, affective, or behavioral outcomes at 6 and 12 months. Only 50% of participants in the TD arm returned for the medical follow-up appointment. Returning was associated with site (p < 0.0001), being female (p = 0.047), and not having a true negative result (p < 0.002). Mammography was lower at 12 months among those who had TD and did not return for medical follow-up (70%) compared with those who had TD and returned (86%) and those who had IPD (87%, adjusted p < 0.01).

Conclusion: Telephone disclosure of genetic test results is a reasonable alternative to in-person disclosure, but attention to medical follow-up may remain important for optimizing appropriate use of genetic results.
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http://dx.doi.org/10.1038/s41436-020-0808-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396300PMC
August 2020

Medical Concept Representation Learning from Multi-source Data.

IJCAI (U S) 2019 Jul;2019:4897-4903

Department of Computer and Information Sciences, Temple University, USA.

Representing words as low dimensional vectors is very useful in many natural language processing tasks. This idea has been extended to medical domain where medical codes listed in medical claims are represented as vectors to facilitate exploratory analysis and predictive modeling. However, depending on a type of a medical provider, medical claims can use medical codes from different ontologies or from a combination of ontologies, which complicates learning of the representations. To be able to properly utilize such multi-source medical claim data, we propose an approach that represents medical codes from different ontologies in the same vector space. We first modify the Pointwise Mutual Information (PMI) measure of similarity between the codes. We then develop a new negative sampling method for word2vec model that implicitly factorizes the modified PMI matrix. The new approach was evaluated on the code cross-reference problem, which aims at identifying similar codes across different ontologies. In our experiments, we evaluated cross-referencing between ICD-9 and CPT medical code ontologies. Our results indicate that vector representations of codes learned by the proposed approach provide superior cross-referencing when compared to several existing approaches.
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http://dx.doi.org/10.24963/ijcai.2019/680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047512PMC
July 2019

Longitudinal outcomes with cancer multigene panel testing in previously tested BRCA1/2 negative patients.

Clin Genet 2020 04;97(4):601-609

Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Although multigene panel testing (MGPT) is increasingly utilized in clinical practice, there remain limited data on patient-reported outcomes. BRCA 1/2 negative patients were contacted and offered MGPT. Patients completed pre- and posttest counseling, and surveys assessing cognitive, affective and behavioral outcomes at baseline, postdisclosure and 6 and 12 months. Of 317 eligible BRCA1/2 negative patients who discussed the study with research staff, 249 (79%) enrolled. Decliners were more likely to be older, non-White, and recruited by mail or email. Ninety-five percent of enrolled patients proceeded with MGPT. There were no significant changes in anxiety, depression, cancer specific distress or uncertainty postdisclosure. There were significant but small increases in knowledge, cancer-specific distress and depression at 6-12 months. Uncertainty declined over time. Those with a VUS had significant decreases in uncertainty but also small increases in cancer specific distress at 6 and 12 months. Among those with a positive result, medical management recommendations changed in 26% of cases and 2.6% of all tested. Most BRCA1/2 negative patients have favorable psychosocial outcomes after receipt of MGPT results, although small increases in depression and cancer-specific worry may exist and may vary by result. Medical management changed in few patients.
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http://dx.doi.org/10.1111/cge.13716DOI Listing
April 2020

The development, usability, and reliability of the Electronic Patient Visit Assessment (ePVA) for head and neck cancer.

Mhealth 2019 29;5:21. Epub 2019 Jul 29.

Fox Chase Cancer Center, Philadelphia, PA, USA.

Background: Annually, over 65,000 persons are diagnosed with head and neck cancer in the United States. During treatment, up to 50% of patients become severely symptomatic with pain, fatigue, mouth sores, and inability to eat. Long term complications are lymphedema, fibrosis, dysphagia, and musculoskeletal impairment. Patients' ability to perform daily activities and to interact socially may be impaired, resulting in poor quality of life. A pragmatic, clinically useful assessment is needed to ensure early detection and intervention for patients to report symptoms and functional limitations over time. We developed the Electronic Patient Visit Assessment (ePVA) that enables patients to report 42 symptoms related to head and neck cancer and 17 limitations of functional status. This manuscript reports (I) the development of the ePVA, (II) the content validity of the ePVA, and (III) the usability and reliability of the ePVA.

Methods: Usability was evaluated using the "Think Aloud" technique to guide the iterative process to refine the ePVA based on participants' evaluations. After signing the informed consent, 30 participants with head and neck cancer completed the ePVA using digital tablet devices while thinking aloud about ease of use. All patient conversations were recorded and professionally transcribed. Reliability of the ePVA symptom and functional limitation measures was estimated using the Kuder-Richardson test. Convergent validity of the ePVA was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global QoL/health scale. Transcribed qualitative data were analyzed using directed content analysis approach. Quantitative analyses consisted of descriptive statistics and correlation analyses.

Results: Among participants, 90% strongly agreed or agreed that the ePVA system was easy to use and 80% were very satisfied. Only minor usability problems were reported due to formatting and software "bugs". Reporting of usability problems decreased in frequency over the study period and no usability problems were reported by the last 3 participants who completed the ePVA. Based on participants' suggestions during the iterative process, refinement of the ePVA included increased touch sensitivity of the touch screen technology and customized error messages to improve ease of use. The ePVA also recorded patient reported symptoms (mouth symptoms: 93%, fibrosis: 60%, fatigue: 60%). The ePVA demonstrated acceptable reliability (alpha =0.82-0.85) and convergent validity (ePVA total number of reported symptoms and function limitations was negatively correlated with EORTC QLQ-C30 global QOL/health scale: r=-0.55038, P<0.01).

Conclusions: The ePVA was rigorously developed, accepted by patients with satisfaction, and demonstrated acceptable reliability and convergent validity. Future research will use data generated by the ePVA to determine the impact of symptom trajectories on functional status, treatment interruptions and terminations, and health resource use in head and neck cancer.
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http://dx.doi.org/10.21037/mhealth.2019.06.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691072PMC
July 2019

Inflammation and breast density among female Chinese immigrants: exploring variations across neighborhoods.

Cancer Causes Control 2019 Oct 7;30(10):1113-1126. Epub 2019 Aug 7.

Department of Kinesiology and Public Health, California Polytechnic State University, 1 Grand Avenue, San Luis Obispo, CA, 93407, USA.

Purpose: We examined associations of inflammation with breast density, a marker of breast cancer risk, among female Chinese immigrants and explored whether associations varied by neighborhood environment.

Methods: Assessments of serum C-reactive protein (CRP), soluble tumor necrosis factor receptor 2 (sTNFR2), and breast density were performed among 401 Chinese immigrants across the Philadelphia region. Participant addresses were geocoded, with the majority residing in areas representing traditional urban enclaves (i.e., Chinatown and South Philadelphia) or an emerging enclave with a smaller, but rapidly growing Chinese immigrant population (i.e., the Near Northeast). The remainder was classified as residing in non-enclaves.

Results: In multivariable adjusted regression models, CRP was inversely associated with dense breast area (p = 0.01). Levels of sTNFR2 were also inversely associated with dense breast area, but these associations varied by neighborhood (interaction p = 0.01); specifically, inverse associations were observed among women residing in the emerging enclave (p = 0.03), but not other neighborhoods.

Conclusions: Among Chinese immigrant women, aggregate analyses that do not take neighborhood context into consideration can mask potential variations in association of inflammatory markers with breast density. Future studies should consider how neighborhood contextual factors may contribute to differential risk pathways.
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http://dx.doi.org/10.1007/s10552-019-01206-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745706PMC
October 2019

Research participants' experiences with return of genetic research results and preferences for web-based alternatives.

Mol Genet Genomic Med 2019 09 3;7(9):e898. Epub 2019 Aug 3.

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.

Background: While there is increasing interest in sharing genetic research results with participants, how best to communicate the risks, benefits and limitations of research results remains unclear.

Methods: Participants who received genetic research results answered open and closed-ended questions about their experiences receiving results and interest in and advantages and disadvantages of a web-based alternative to genetic counseling.

Results: 107 BRCA1/2 negative women with a personal or family history of breast cancer consented to receive genetic research results and 82% completed survey items about their experience. Most participants reported there was nothing they disliked (74%) or would change (85%) about their predisclosure or disclosure session (78% and 89%). They most frequently reported liking the genetic counselor and learning new information. Only 24% and 26% would not be willing to complete predisclosure counseling or disclosure of results by a web-based alternative, respectively. The most frequently reported advantages included convenience and reduced time. Disadvantages included not being able to ask questions, the risk of misunderstanding and the impersonal nature of the encounter.

Conclusion: Most participants receiving genetic research results report high satisfaction with telephone genetic counseling, but some may be willing to consider self-directed web alternatives for both predisclosure genetic education and return of results.
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http://dx.doi.org/10.1002/mgg3.898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732272PMC
September 2019

Trends in Regionalization of Care and Mortality For Patients Treated With Radical Cystectomy.

Med Care 2019 09;57(9):728-733

Fox Chase Cancer Center, Philadelphia, PA.

Background: Regionalization to higher volume centers has been proposed as a mechanism to improve short-term outcomes following complex surgery.

Objective: The objective of this study was to assess trends in regionalization and mortality for patients undergoing radical cystectomy (RC).

Research Design: An observational study of patients receiving RC in the United States from 2004 to 2013.

Subjects: Data for patients receiving RC were extracted from the National Cancer Database.

Measures: The primary exposure was hospital volume; low-volume hospitals (LVH) included those with <5 RC/year and high-volume hospitals (HVH) were those with ≥30 RC/year. Trends in the volume were assessed, as were 30- and 90-day mortality. Cochrane-Armitage tests were performed for volume, and propensity score-weighted proportional hazard regression was used to assess mortality.

Results: A total of 47,028 RC were performed in 1162 hospitals from 2004 to 2013. The proportion of RC at LVH declined from 29% to 17% (P<0.01), whereas that of HVH increased from 16% to 33% (P<0.01). Unadjusted 30- (P=0.02) and 90-day (P<0.001) mortality decreased, and the absolute decrease was greatest at LVH (4.8% vs. 2.6%, P=0.03), whereas rates for HVH remained stable (1.9% vs. 1.4%, P=0.34). Following risk-adjustment, relative to treatment at HVH, treatment at LVH was associated with increased 30-day (hazard ratio: 1.66, 95% CI: 1.53-1.80) and 90-day mortality (hazard ratio: 1.37, 95% confidence interval: 1.30-1.44).

Conclusions: Regionalization of RC to HVH was observed from 2004 to 2013. Treatment at LVH was associated with 66% and 33% relative increases in hazard of death at 30 and 90 days, respectively. These findings support the selective referral of complex cases to higher volume centers.
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http://dx.doi.org/10.1097/MLR.0000000000001143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537145PMC
September 2019

Prediction of significant estimated glomerular filtration rate decline after renal unit removal to aid in the clinical choice between radical and partial nephrectomy in patients with a renal mass and normal renal function.

BJU Int 2019 12 30;124(6):999-1005. Epub 2019 Jun 30.

Fox Chase Cancer Center, Philadelphia, PA, USA.

Objectives: To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN).

Patients And Methods: Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit.

Results: A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m . On multivariable analysis, increasing age (P = 0.001), female gender (P < 0.001), and increasing preoperative creatinine level (P < 0.001) were associated with functional decline. We constructed a predictive nomogram that included these variables in addition to comorbidities with a known association with kidney disease, but found that a simplified model excluding comorbidities was equally robust (cross-validated area under the ROC curve was 0.78). Decision-curve analysis showed the net clinical benefit at probabilities >~11%.

Conclusions: The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m , who may be stronger candidates for nephron preservation.
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http://dx.doi.org/10.1111/bju.14839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654970PMC
December 2019

Interpretable Representation Learning for Healthcare via Capturing Disease Progression through Time.

KDD 2018 Aug;2018:43-51

Temple University, Philadelphia, PA, USA

Various deep learning models have recently been applied to predictive modeling of Electronic Health Records (EHR). In medical claims data, which is a particular type of EHR data, each patient is represented as a sequence of temporally ordered irregularly sampled visits to health providers, where each visit is recorded as an unordered set of medical codes specifying patient's diagnosis and treatment provided during the visit. Based on the observation that different patient conditions have different temporal progression patterns, in this paper we propose a novel interpretable deep learning model, called Timeline. The main novelty of Timeline is that it has a mechanism that learns time decay factors for every medical code. This allows the Timeline to learn that chronic conditions have a longer lasting impact on future visits than acute conditions. Timeline also has an attention mechanism that improves vector embeddings of visits. By analyzing the attention weights and disease progression functions of Timeline, it is possible to interpret the predictions and understand how risks of future visits change over time. We evaluated Timeline on two large-scale real world data sets. The specific task was to predict what is the primary diagnosis category for the next hospital visit given previous visits. Our results show that Timeline has higher accuracy than the state of the art deep learning models based on RNN. In addition, we demonstrate that time decay factors and attentions learned by Timeline are in accord with the medical knowledge and that Timeline can provide a useful insight into its predictions.
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http://dx.doi.org/10.1145/3219819.3219904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484836PMC
August 2018

Common Pitfalls of Head and Neck Research Using Cancer Registries.

Otolaryngol Head Neck Surg 2019 08 2;161(2):245-250. Epub 2019 Apr 2.

1 Department of Otolaryngology, Lewis Katz School of Medicine of Temple University, Philadelphia, Pennsylvania, USA.

Objective: To highlight common pitfalls observed in scientific research derived from national cancer registries, predominantly the Survival, Epidemiology, and End Results Program and the National Cancer Database.

Data Sources: Literature review and expert opinion.

Review Methods: This state-of-the-art review consolidates the literature with editorial experiences describing how and why statistically flawed studies are usually rejected for publication, highlighting common errors in submitted articles employing national cancer registries.

Conclusions: Pitfalls were identified in 2 major areas-design and data analysis. Design pitfalls included unbalanced cohorts, uncontrolled covariates, and flawed oncologic variables. Analytical pitfalls included incorrect application of univariate analyses, inclusion of inaccurate data, and inclusion of stage IVc disease in curative survival analysis. Additional limitations of database studies were identified, including absence of patient-related outcomes, hypothesis-generating vs practice-changing implications, and inability to differentiate between overall survival and disease-specific survival.

Implications For Practice: Methodological strategies are suggested to ensure careful analytical design and appropriate interpretation. Although national cancer registries provide a wealth of data, researchers must remain vigilant when designing studies and analyzing these data sets. Inherent design flaws raise considerable problems with interpretation; however, when analyzed judiciously, registries can lead to a better understanding of cancer outcomes.
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http://dx.doi.org/10.1177/0194599819838823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580692PMC
August 2019

EHR phenotyping via jointly embedding medical concepts and words into a unified vector space.

BMC Med Inform Decis Mak 2018 12 12;18(Suppl 4):123. Epub 2018 Dec 12.

Department of Computer & Information Sciences, Temple University, Philadelphia, PA, USA.

Background: There has been an increasing interest in learning low-dimensional vector representations of medical concepts from Electronic Health Records (EHRs). Vector representations of medical concepts facilitate exploratory analysis and predictive modeling of EHR data to gain insights about the patterns of care and health outcomes. EHRs contain structured data such as diagnostic codes and laboratory tests, as well as unstructured free text data in form of clinical notes, which provide more detail about condition and treatment of patients.

Methods: In this work, we propose a method that jointly learns vector representations of medical concepts and words. This is achieved by a novel learning scheme based on the word2vec model. Our model learns those relationships by integrating clinical notes and sets of accompanying medical codes and by defining joint contexts for each observed word and medical code.

Results: In our experiments, we learned joint representations using MIMIC-III data. Using the learned representations of words and medical codes, we evaluated phenotypes for 6 diseases discovered by our and baseline method. The experimental results show that for each of the 6 diseases our method finds highly relevant words. We also show that our representations can be very useful when predicting the reason for the next visit.

Conclusions: The jointly learned representations of medical concepts and words capture not only similarity between codes or words themselves, but also similarity between codes and words. They can be used to extract phenotypes of different diseases. The representations learned by the joint model are also useful for construction of patient features.
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http://dx.doi.org/10.1186/s12911-018-0672-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290514PMC
December 2018

Preferences for in-person disclosure: Patients declining telephone disclosure characteristics and outcomes in the multicenter Communication Of GENetic Test Results by Telephone study.

Clin Genet 2019 02 7;95(2):293-301. Epub 2018 Dec 7.

Division of Hematology-Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois.

Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.
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http://dx.doi.org/10.1111/cge.13474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453119PMC
February 2019

Temporal trends and characteristics of clinical trials for which only one racial or ethnic group is eligible.

Contemp Clin Trials Commun 2018 Mar 31;9:135-142. Epub 2018 Jan 31.

Fox Chase Cancer Center, Temple University Health System, 333 Cottman Ave., Philadelphia, PA 19111, USA.

Background: Increasing diversity in clinical trials may be worthwhile. We examined clinical trials that restricted eligibility to a single race or ethnicity.

Methods: We reviewed 19,246 trials registered on ClinicalTrials.gov through January 2013. We mapped trial ZIP-codes to U.S. Census and American Community Survey data. The outcome was whether trials required participants to be from a single racial or ethnic group.

Results: In adjusted analyses, the odds of trials restricting eligibility to a single race/ethnicity increased by 4% per year (95% CI 1.01-1.08, p = .024). Behavioral (5.79% with single race/ethnicity requirements), skin-related (4.49%), and Vitamin D (6.14%) studies had higher rates of single race/ethnicity requirements. Many other trial-specific characteristics, such as funding agency and region of the U.S. in which the trial opened, were associated with eligibility restrictions. In terms of neighborhood characteristics, studies with single race eligibility requirements were more likely to be located in ZIP-codes with greater percentages of those self-reporting the characteristic. For example, 35.2% (SD = 24.9%) of the population self-reported themselves as Black or African American in ZIP-codes with trials requiring participants to be Black/African American, but only 5.9% (SD = 6.9%) self-reported themselves as Black/African American in ZIP-codes with trials that required Asian ethnicity. In ZIP-codes with trials requiring Asian ethnicity, 24.6% (SD = 16.2%) self-reported as Asian. In ZIP-codes with trials requiring Hispanic/Latino ethnicity, 33.3% (SD = 28.5%) self-reported as Hispanic/Latino. Neighborhood level poverty rates and reduced English language ability were also associated with more single race eligibility requirements.

Conclusions: In selected fields, there has been a modest temporal increase in single race/ethnicity inclusion requirements. Some studies may not fall under regulatory purview and hence may be less likely to include diverse samples. Conversely, some eligibility requirements may be related to health disparities research. Future work should examine whether targeted enrollment criteria facilitates development of personalized medicine or reduces trial access.
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http://dx.doi.org/10.1016/j.conctc.2018.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898501PMC
March 2018

Randomized Noninferiority Trial of Telephone vs In-Person Disclosure of Germline Cancer Genetic Test Results.

J Natl Cancer Inst 2018 09;110(9):985-993

Division of Hematology-Oncology and Section of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, and Center for Clinical Cancer Genetics and Global Health, The University of Chicago, Chicago, IL.

Background: Germline genetic testing is standard practice in oncology. Outcomes of telephone disclosure of a wide range of cancer genetic test results, including multigene panel testing (MGPT) are unknown.

Methods: Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone disclosure (TD) of genetic test results with usual care, in-person disclosure (IPD) after tiered-binned in-person pretest counseling. Primary noninferiority outcomes included change in knowledge, state anxiety, and general anxiety. Secondary outcomes included cancer-specific distress, depression, uncertainty, satisfaction, and screening and risk-reducing surgery intentions. To declare noninferiority, we calculated the 98.3% one-sided confidence interval of the standardized effect; t tests were used for secondary subgroup analyses. Only noninferiority tests were one-sided, others were two-sided.

Results: A total of 1178 patients enrolled in the study. Two hundred eight (17.7%) participants declined random assignment due to a preference for in-person disclosure; 473 participants were randomly assigned to TD and 497 to IPD; 291 (30.0%) had MGPT. TD was noninferior to IPD for general and state anxiety and all secondary outcomes immediately postdisclosure. TD did not meet the noninferiority threshold for knowledge in the primary analysis, but it did meet the threshold in the multiple imputation analysis. In secondary analyses, there were no statistically significant differences between arms in screening and risk-reducing surgery intentions, and no statistically significant differences in outcomes by arm among those who had MGPT. In subgroup analyses, patients with a positive result had statistically significantly greater decreases in general anxiety with telephone disclosure (TD -0.37 vs IPD +0.87, P = .02).

Conclusions: Even in the era of multigene panel testing, these data suggest that telephone disclosure of cancer genetic test results is as an alternative to in-person disclosure for interested patients after in-person pretest counseling with a genetic counselor.
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http://dx.doi.org/10.1093/jnci/djy015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136932PMC
September 2018

Statins Synergize with Hedgehog Pathway Inhibitors for Treatment of Medulloblastoma.

Clin Cancer Res 2018 03 6;24(6):1375-1388. Epub 2018 Feb 6.

Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.

The role of cholesterol biosynthesis in hedgehog pathway activity and progression of hedgehog pathway medulloblastoma (Hh-MB) were examined Statins, commonly used cholesterol-lowering agents, were utilized to validate cholesterol biosynthesis as a therapeutic target for Hh-MB. Bioinformatic analysis was performed to evaluate the association between cholesterol biosynthesis with hedgehog group medulloblastoma in human biospecimens. Alterations in hedgehog signaling were evaluated in medulloblastoma cells after inhibition of cholesterol biosynthesis. The progression of endogenous medulloblastoma in mice was examined after genetic blockage of cholesterol biosynthesis in tumor cells. Statins alone, or in combination with vismodegib (an FDA-approved Smoothened antagonist), were utilized to inhibit medulloblastoma growth Cholesterol biosynthesis was markedly enhanced in Hh-MB from both humans and mice. Inhibition of cholesterol biosynthesis dramatically decreased Hh pathway activity and reduced proliferation of medulloblastoma cells. Statins effectively inhibited medulloblastoma growth and functioned synergistically in combination with vismodegib. Cholesterol biosynthesis is required for Smoothened activity in the hedgehog pathway, and it is indispensable for the growth of Hh-MB. Targeting cholesterol biosynthesis represents a promising strategy for treatment of Hh-MB. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856627PMC
March 2018

Joint Learning of Representations of Medical Concepts and Words from EHR Data.

Proceedings (IEEE Int Conf Bioinformatics Biomed) 2017 Nov 18;2017:764-769. Epub 2017 Dec 18.

Department of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA.

There has been an increasing interest in learning low-dimensional vector representations of medical concepts from electronic health records (EHRs). While EHRs contain structured data such as diagnostic codes and laboratory tests, they also contain unstructured clinical notes, which provide more nuanced details on a patient's health status. In this work, we propose a method that jointly learns medical concept and word representations. In particular, we focus on capturing the relationship between medical codes and words by using a novel learning scheme for word2vec model. Our method exploits relationships between different parts of EHRs in the same visit and embeds both codes and words in the same continuous vector space. In the end, we are able to derive clusters which reflect distinct disease and treatment patterns. In our experiments, we qualitatively show how our methods of grouping words for given diagnostic codes compares with a topic modeling approach. We also test how well our representations can be used to predict disease patterns of the next visit. The results show that our approach outperforms several common methods.
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http://dx.doi.org/10.1109/BIBM.2017.8217752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783648PMC
November 2017

Returning Individual Genetic Research Results to Research Participants: Uptake and Outcomes Among Patients With Breast Cancer.

JCO Precis Oncol 2018 16;2. Epub 2018 Apr 16.

Angela R. Bradbury, Kara N. Maxwell, Laura DiGiovanni, Jamie Brower, Dominique Fetzer, Jill Bennett Gaieski, Amanda Brandt, Danielle McKenna, Jessica Long, Jacquelyn Powers, Jill E. Stopfer, Katherine L. Nathanson, and Susan M. Domchek, Perelman School of Medicine at the University of Pennsylvania; Brian L. Egleston, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA; and Linda Patrick-Miller, The University of Chicago, Chicago, IL.

Purpose: Understanding the outcomes of returning individual genetic research results to participants is critical because some genetic variants are found to be associated with health outcomes and have become available for clinical testing.

Materials And Methods: -negative women with early-onset breast cancer, multiple primary cancers, or a family history of breast cancer who participated in a gene discovery cancer registry were offered the opportunity to learn their individual genetic research results of 24 breast cancer susceptibility genes with a genetic counselor after predisclosure genetic counseling. Outcomes included uptake of research results, knowledge, informed choice, psychosocial adjustment, uncertainty, satisfaction, and uptake of clinical confirmation testing.

Results: Four hundred two potential participants were contacted. One hundred ninety-four participants (48%) did not respond despite multiple attempts, and 85 participants (21%) actively or passively declined. One hundred seven participants (27%) elected for predisclosure counseling and were more likely to be younger, married, and white. Ninety percent of participants who had predisclosure counseling elected to receive their genetic research results, and 89% made an informed choice. Knowledge increased significantly after predisclosure counseling, and anxiety, intrusive cancer-specific distress, uncertainty, and depression declined significantly after receipt of results. General anxiety and intrusive cancer-specific distress declined significantly for both participants with a positive result and those with a negative result. Sixty-four percent of participants had clinical confirmation testing when recommended, including all participants with a mutation in a high-penetrance gene.

Conclusion: Uptake of genetic research results may be lower than anticipated by hypothetical reports and small select studies. Participants who elected to receive research results with genetic providers did not experience increases in distress or uncertainty, but not all patients return for confirmation testing.
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http://dx.doi.org/10.1200/po.17.00250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039346PMC
April 2018

Use and Patient-Reported Outcomes of Clinical Multigene Panel Testing for Cancer Susceptibility in the Multicenter Communication of Genetic Test Results by Telephone Study.

JCO Precis Oncol 2018 18;2. Epub 2018 Dec 18.

University of Pennsylvania.

Purpose: Multigene panels (MGPs) are increasingly being used despite questions regarding their clinical utility and no standard approach to genetic counseling. How frequently genetic providers use MGP testing and how patient-reported outcomes (PROs) differ from targeted testing (eg, only) are unknown.

Methods: We evaluated use of MGP testing and PROs in participants undergoing cancer genetic testing in the multicenter Communication of Genetic Test Results by Telephone study (ClinicalTrials.gov identifier: ), a randomized study of telephone versus in-person disclosure of genetic test results. PROs included genetic knowledge, general and state anxiety, depression, cancer-specific distress, uncertainty, and satisfaction. Genetic providers offered targeted or MGP testing based on clinical assessment.

Results: Since the inclusion of MGP testing in 2014, 395 patients (66%) were offered MGP testing. MGP testing increased over time from 57% in 2014 to 66% in 2015 ( = .02) and varied by site (46% to 78%; < .01). Being offered MGP testing was significantly associated with not having Ashkenazi Jewish ancestry, having a history of cancer, not having a mutation in the family, not having made a treatment decision, and study site. After demographic adjustment, patients offered MGP testing had lower general anxiety ( = .04), state anxiety ( = .03), depression ( = .04), and uncertainty ( = .05) pre-disclosure compared with patients offered targeted testing. State anxiety ( = .05) and cancer-specific distress ( = .05) were lower at disclosure in the MGP group. There was a greater increase in change in uncertainty ( = .04) among patients who underwent MGP testing.

Conclusion: MGP testing was more frequently offered to patients with lower anxiety, depression, and uncertainty and was associated with favorable outcomes, with the exception of a greater increase in uncertainty compared with patients who had targeted testing. Addressing uncertainty may be important as MGP testing is increasingly adopted.
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http://dx.doi.org/10.1200/PO.18.00199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901130PMC
December 2018

On the Use of Summary Comorbidity Measures for Prognosis and Survival Treatment Effect Estimation.

Health Serv Outcomes Res Methodol 2017 Dec 21;17(3-4):237-255. Epub 2017 Jun 21.

Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania, 19111, U.S.A., Telephone: (215) 214-3917.

Prognostic scores have been proposed as outcome based confounder adjustment scores akin to propensity scores. However, prognostic scores have not been widely used in the substantive literature. Instead, comorbidity scores, which are limited versions of prognostic scores, have been used extensively by clinical and health services researchers. A comorbidity is an existing disease an individual has in addition to a primary condition of interest, such as cancer. Comorbidity scores are used to reduce the dimension of a vector of comorbidity variables into a single scalar variable. Such scores are often added to regression models with other non-comorbidity variables such as age and sex, both for analyzing prognosis and for confounder adjustment when analyzing treatment effects. Despite their widespread use, the properties of and conditions under which comorbidity scores are valid dimension reduction tools in statistical models is largely unknown. In this article, we show that under relatively standard assumptions, comorbidity scores can have equal prognostic and confounder-adjustment abilities as the individual comorbidity variables, but that biases can occur if there are additional effects, such as interactions, of covariates beyond that captured by the comorbidity score. Simulations were performed to illustrate empirical properties and a data example using breast cancer data from the SEER Medicare Database demonstrates the application of these results.
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http://dx.doi.org/10.1007/s10742-017-0171-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697800PMC
December 2017

Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis.

J Natl Compr Canc Netw 2017 10;15(10):1224-1233

From Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.

Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50-64 years), and elderly (≥65 years). The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (=.003) and buying food (=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (=.016) and DT score (=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (<.001). Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.
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http://dx.doi.org/10.6004/jnccn.2017.0161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569506PMC
October 2017

Latent Class Survival Models Linked by Principal Stratification to Investigate Heterogenous Survival Subgroups Among Individuals With Early-Stage Kidney Cancer.

J Am Stat Assoc 2017 7;112(518):534-546. Epub 2016 Oct 7.

Medical Oncology, Fox Chase Cancer Center, Temple University Health System.

Rates of kidney cancer have been increasing, with small incidental tumors experiencing the fastest growth rates. Much of the increase could be due to increased use of CT scans, MRIs, and ultrasounds for unrelated conditions. Many tumors might never have been detected or become symptomatic in the past. This suggests that many patients might benefit from less aggressive therapy, such as active surveillance by which tumors are surgically removed only if they become sufficiently large. However, it has been difficult for clinicians to identify subgroups of patients for whom treatment might be especially beneficial or harmful. In this work, we use a principal stratification framework to estimate the proportion and characteristics of individuals who have large or small hazard rates of death in two treatment arms. This allows us to assess who might be helped or harmed by aggressive treatment. We also use Weibull mixture models. This work differs from much previous work in that the survival classes upon which principal stratification is based are latent variables. That is, survival class is not an observed variable. We apply this work using Surveillance Epidemiology and End Results-Medicare claims data. Clinicians can use our methods for investigating treatments with heterogeneous effects.
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http://dx.doi.org/10.1080/01621459.2016.1240078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615848PMC
October 2016

Anti-Müllerian hormone and risk of ovarian cancer in nine cohorts.

Int J Cancer 2018 01 4;142(2):262-270. Epub 2017 Oct 4.

Departments of Population Health and Environmental Medicine and Perlmutter Cancer Center, New York University School of Medicine, New York, NY.

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (P : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all P : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all P : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
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http://dx.doi.org/10.1002/ijc.31058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749630PMC
January 2018

Anti-Mullerian hormone and endometrial cancer: a multi-cohort study.

Br J Cancer 2017 Oct 5;117(9):1412-1418. Epub 2017 Sep 5.

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk.

Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (OR). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics.

Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (OR: 1.07 (0.99-1.17)), or with any of the examined subgroups.

Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
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http://dx.doi.org/10.1038/bjc.2017.299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672934PMC
October 2017