Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States.

Intensive chemotherapy (IC) is commonly used to achieve remission in patients with acute myeloid leukemia (AML). Venetoclax plus azacitidine (VEN-AZA) is FDA-approved to treat patients with AML aged ≥ 75 years or who are ineligible for IC. This retrospective analysis used de-identified electronic health records from the US-based Flatiron Health database from patients diagnosed 11/21/2018 to 10/31/2021 to compare treatment outcomes with VEN-AZA vs. IC. Patients were 1:1 propensity score-matched ([Formula: see text]). Assessments included rates of complete remission (CR) and hematopoietic stem cell transplant (HSCT), overall survival (OS), and relapse-free survival (RFS). CR and HSCT rates were higher with IC than with VEN-AZA (60.9% vs. 44.2% [P = 0.006] and 18.1% vs. 8.0% [P = 0.012], respectively). Median OS was 17.7 months in patients treated with IC and 11.3 months with VEN-AZA without censoring (P = 0.278) and 13.7 vs. 10.6 months, respectively, with censoring at HSCT (P = 0.584). Median RFS was 12.0 months in patients treated with IC vs. 9.5 months with VEN-AZA without censoring (P = 0.431) and 6.4 vs. 7.4 months, respectively, with censoring at HSCT (P = 0.444). No OS or RFS differences observed between the two arms reached statistical significance. Randomized controlled trials comparing the two approaches are warranted, as are novel approaches to reduce relapse rates following CR.

Real-world analysis of insurance churn among young adults with schizophrenia using the Colorado All-Payer Claims Database.

BACKGROUND: Most patients with schizophrenia are diagnosed in their early twenties and often have commercial insurance at diagnosis. These young adults can experience changes in insurance coverage, that is, "churn," which can lead to disruptions in care. OBJECTIVE: To examine the frequency, speed, and type of insurance churn events in a young adult schizophrenia population with commercial insurance coverage at diagnosis. METHODS: The Colorado All-Payer Claims Database, containing insurance claims data from commercial and public insurers for Colorado residents, was used for the study. Eligible patients were required to have at least 1 inpatient or 2 outpatient claims for schizophrenia or schizoaffective disorder, be of age 18-34 years at index, have previous insurance coverage for 12 consecutive months, and have commercial insurance at diagnosis. These patients were 1:5 propensity score matched (PSM) with nonschizophrenia members. Percentages of members on different insurance types were calculated monthly to assess churn events. Cohorts were compared using descriptive statistics, Cox proportional hazards, and generalized estimating equation models. RESULTS: The matched schizophrenia and nonschizophrenia cohorts comprised 501 and 2,510 members, respectively. Before PSM, cohorts were imbalanced (schizophrenia cohort had a younger median age and higher proportion of males). After matching, the cohorts were similar in terms of the matched baseline characteristics. Previous mental health disorders were more common in the schizophrenia cohort (75%) than in the nonschizophrenia cohort (26%). The proportion of members with at least 1 churn event for the schizophrenia and nonschizophrenia cohorts, respectively, were 53.8% vs 36.5% after 12 months and 84.6% vs 69.2% after 48 months. Time to first churn event was significantly shorter in the schizophrenia cohort (16 months) than the nonschizophrenia cohort (23 months; P < 0.001). Schizophrenia cohort members had 64.1 and 56.8 churn events per 1,000 members per month vs 43.0 (P ≤ 0.001) and 42.8 (P = 0.011) churn events for nonschizophrenia cohort members in the first and second 6-month periods, respectively. Proportions of members in the schizophrenia and nonschizophrenia cohorts on public insurance, respectively, were 22.9% vs 6.9% after 12 months and 52.4% and 10.7% after 48 months. In the schizophrenia cohort, the most common churn event type was from commercial to public insurance rather than to a different commercial insurance; notably, 41% of members were still on a commercial plan 4 years after diagnosis. CONCLUSIONS: Young adults with schizophrenia experienced churn events more rapidly and more frequently than those without schizophrenia for the first 4 years studied after the index date. These disruptions may be associated with reduced access to care and treatment gaps in this vulnerable patient population. DISCLOSURES: This research was sponsored by Janssen Scientific Affairs, LLC. Pesa, Benson, and Patel are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. Potluri, Rotter, and Papademetriou are employees of SmartAnalyst Inc, and their work on this study was funded by Janssen Pharmaceuticals. A version of this study was presented as a poster at the Psych Congress 2020 Virtual Experience, September 10-13, 2020.

Economic burden to commercial payers of young adults with schizophrenia in Colorado.

AIMS: The primary objective was to examine direct costs and health resource utilization (HRU) among commercially insured young adults with schizophrenia (SCZ) in Colorado. MATERIALS AND METHODS: The Colorado All-Payer Claims Database, covering approximately 76% of the insured Colorado population was used. Members aged 18-34, with and without SCZ, having commercial insurance were included. All-cause, mental health (MH) related and non-MH related per patient per month (PPPM) costs and per hundred patients per month (PHPPM) HRU were compared between an SCZ cohort and a propensity score matched non-SCZ cohort before and after index date up to 48 months. RESULTS: Five hundred and one patients with SCZ and 2,510 matched individuals without SCZ were included. HRU and costs were higher for SCZ patients both pre- and post-index date. Pre-index, there were 32.3 (24.0 MH; 8.4 non-MH) PHPPM more office visits; 2.1 (2.7 MH) PHPPM more admissions; 104.8 (67.02 MH; 37.7 non-MH) PHPPM more prescriptions in the SCZ cohort (all p<.01). After index date, the SCZ cohort had 89.6 (81.3 MH; 9.2 non-MH) more PHPPM office visits, 7.2 (6.1 MH; 0.9 non-MH) PHPPM more admissions, and 181.6 (123.1 MH; 58.6 non-MH) PHPPM more prescriptions (all p<.001). All-cause costs in the pre-index period were $457 PPPM ($373 MH) higher for the SCZ cohort (p<.001). In the post-index period, all-cause costs for the SCZ cohort were $1,687 PPPM ($1,258 MH; $412 non-MH) higher (all p<.001). Approximately, 40% of patients with SCZ were on commercial insurance after four years compared with approximately 75% in the non-SCZ cohort. LIMITATIONS: This study was based on data from a single state, thus may not be generalizable to other states. CONCLUSIONS: Healthcare costs and HRU for young adults diagnosed with SCZ are significantly more burdensome to commercial payers than matched patients without SCZ, both before and after an official SCZ diagnosis.

How well do clinical and demographic characteristics predict Patient Health Questionnaire-9 scores among patients with treatment-resistant major depressive disorder in a real-world setting?

OBJECTIVES: To create and validate a model to predict depression symptom severity among patients with treatment-resistant depression (TRD) using commonly recorded variables within medical claims databases. METHODS: Adults with TRD (here defined as > 2 antidepressant treatments in an episode, suggestive of nonresponse) and ≥ 1 Patient Health Questionnaire (PHQ)-9 record on or after the index TRD date were identified (2013-2018) in Decision Resource Group's Real World Data Repository, which links an electronic health record database to a medical claims database. A total of 116 clinical/demographic variables were utilized as predictors of the study outcome of depression symptom severity, which was measured by PHQ-9 total score category (score: 0-9 = none to mild, 10-14 = moderate, 15-27 = moderately severe to severe). A random forest approach was applied to develop and validate the predictive model. RESULTS: Among 5,356 PHQ-9 scores in the study population, the mean (standard deviation) PHQ-9 score was 10.1 (7.2). The model yielded an accuracy of 62.7%. For each predicted depression symptom severity category, the mean observed scores (8.0, 12.2, and 16.2) fell within the appropriate range. CONCLUSIONS: While there is room for improvement in its accuracy, the use of a machine learning tool that predicts depression symptom severity of patients with TRD can potentially have wide population-level applications. Healthcare systems and payers can build upon this groundwork and use the variables identified and the predictive modeling approach to create an algorithm specific to their population.

Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.

The Real-World Medicare Costs of Alzheimer Disease: Considerations for Policy and Care.

BACKGROUND: Headlines in popular media suggest that Alzheimer disease will bankrupt the Medicare program. Indeed, Alzheimer disease affects more than 5 million older Medicare beneficiaries. OBJECTIVE: To compare total Medicare-covered (allowed) costs of patients with Alzheimer disease with the risk adjusted costs of beneficiaries without dementia over their last years of life, using claims data. METHODS: Using the Medicare 5 Percent Limited Data Set claim files from 2006-2015, we conducted a cost impact analysis of costs for up to 8 years before the year of death. Risk adjustment was performed at a beneficiary level using Medicare's 2015 Hierarchical Condition Categories. Beneficiaries were classified into dementia categories based on their diagnoses during the last 3 years of life. Costs were trend adjusted to 2015. RESULTS: This study found that 40% of deceased beneficiaries have Alzheimer disease or unspecified dementia diagnoses in their claims history. In their last 9 years of life, Alzheimer disease added about 11% to the average $17,000 per year Medicare cost for same-risk beneficiaries without dementia. CONCLUSIONS: Like many diseases, Alzheimer disease and dementia are associated with aging, but unlike other diseases, families and Medicaid, rather than Medicare, bear most of the substantial cost burden. As research continues into Alzheimer treatments, it is not too early to consider how to better integrate Medicare and Medicaid to fund and improve patient outcomes, which will likely involve better diagnosis, treatment, and care coordination. DISCLOSURES: Funding for this project was provided by the Alliance for Aging Research, which received funding from Biogen, Eli Lilly, and Janssen Pharmaceuticals. Peschin and Jenkins are employed by the Alliance for Aging Research. Scott was employed by the Alliance for Aging Research at the time of this study and also reports consulting fees from Piramal Imaging, General Electric, and Allergan, outside of this study. Scott is chair of the Board of Directors for the Alliance for Aging Research, which is a volunteer position, and is also president of Applied Policy, a health policy and reimbursement consultancy. Pyenson and Steffens are employed by Milliman, which was contracted to work on this study. Goss Sawhney and Rotter were employed by Milliman at the time this work was performed. Milliman is a consultant to thousands of organizations in the health care industry.

Determinants of Abnormal Cervical Cancer Screening Follow-Up And Invasive Cervical Cancer Among Uninsured and Underinsured Women in New Jersey.

OBJECTIVES: To identify determinants of follow-up care and diagnosis of invasive cervical cancer among uninsured/underinsured women screened for cervical cancer. METHODS: We examined the associations between health care facility, area-level, and individual-level factors on the outcomes of interest in retrospective cohort of women from the New Jersey Cancer Education and Early Detection Program (2000-2015). RESULTS: Women screened at department of health clinics (aOR:3.11, 95% CI: 2.30-4.20) and health care system-affiliated clinics (aOR:1.71, 95% CI: 1.11-2.64) had higher odds of lacking follow-up care compared with women in private physician practices. Similarly, women residing in areas with the highest unemployment had higher odds of lacking follow-up (aOR:1.48, 95% CI: 1.07-2.06). Delays in follow-up care were higher for women born in Central/South American countries compared with U.S.-born women (aOR: 1.46, 95% CI: 1.12-1.92). CONCLUSIONS: Improved outreach efforts and multilevel strategies are needed to address the persistent barriers to appropriate follow-up care for underserved women.

Levels of emotional awareness during psychotherapy among gynecologic cancer patients.

OBJECTIVE: Emotional awareness is the ability to recognize, describe, and attend to emotions. A known correlate is emotional processing, the ability to orient to and use inner experiences for information. The goal was to examine emotional awareness during therapy among gynecologic cancer patients, identify baseline predictors, and explore the relationship between in-session emotional awareness and processing. METHOD: Psychotherapy and baseline data from a randomized controlled trial comparing a supportive counseling (SC) intervention and a cognitive-behavioral coping and communication (CCI) intervention were used. The sample was patients with gynecologic cancers randomized to either therapy (N = 246). Emotion episode transcripts from the first, middle, and sixth of seven in-person sessions were coded for emotional awareness using the Program for Open-Ended Scoring and emotional processing using the Experiencing Scale. Descriptive and regression analyses were conducted.ResultParticipants had moderate in-session emotional awareness. SC participants exhibited higher levels of awareness in the first (p < 0.001) and sixth (p = 0.002) sessions than CCI participants. Awareness was positively correlated with emotional processing in the first and sixth SC sessions (r = 0.25 and 0.24, respectively) and all CCI sessions (r = 0.29-0.31). Baseline negative emotion expression was associated with awareness during the sixth SC session. Baseline cancer-specific distress was associated with awareness during the sixth CCI session.Significance of resultsSC may facilitate emotional awareness. Greater emotional awareness in therapy may facilitate emotional processing, which is an important component of most psychotherapies. Patients who are psychologically distressed may exhibit more awareness than others. Similarly, greater emotional awareness may signal greater patient distress.

Regulator of Calcineurin 1 helps coordinate whole-body metabolism and thermogenesis.

Increasing non-shivering thermogenesis (NST), which expends calories as heat rather than storing them as fat, is championed as an effective way to combat obesity and metabolic disease. Innate mechanisms constraining the capacity for NST present a fundamental limitation to this approach, yet are not well understood. Here, we provide evidence that Regulator of Calcineurin 1 (RCAN1), a feedback inhibitor of the calcium-activated protein phosphatase calcineurin (CN), acts to suppress two distinctly different mechanisms of non-shivering thermogenesis (NST): one involving the activation of UCP1 expression in white adipose tissue, the other mediated by sarcolipin (SLN) in skeletal muscle. UCP1 generates heat at the expense of reducing ATP production, whereas SLN increases ATP consumption to generate heat. Gene expression profiles demonstrate a high correlation between Rcan1 expression and metabolic syndrome. On an evolutionary timescale, in the context of limited food resources, systemic suppression of prolonged NST by RCAN1 might have been beneficial; however, in the face of caloric abundance, RCAN1-mediated suppression of these adaptive avenues of energy expenditure may now contribute to the growing epidemic of obesity.

Receipt of recommended surveillance with imaging in elderly survivors of early stage non-small cell lung cancer.

PURPOSE: Early-stage lung cancer survivorsremain at high risk for recurrence or second cancers. We measured the rates and determinants of regular surveillance imaging in early-stage non-small cell lung cancer (NSCLC) survivors. METHODS: Patients (diagnosed 2001-2011) with resected stage I and II NSCLC were identified from the Surveillance Epidemiology and End Results (SEER)-Medicare linked database. Patients were censored at recurrence/second cancer diagnosis, loss to follow-up or death. Receipt of a scan during the surveillance periods of 7-18, 19-30, 31-42 and 43-60 months from date of surgery was assessed. RESULTS: Of 10,680 survivors assessed during the 18-month surveillance period, 71% received imaging in first 18 months. Only 56% and 43% continued to receive regular imaging by 30-month and 60-month of follow-up, respectively. Survivors were less likely to receive imaging if they were older, black, unmarried, received no adjuvant therapy, had stage I disease (vs. stage II) or were diagnosed before 2006. In adjusted analysis, survivors who received recommended imaging up to 18 months from surgery experienced better survival compared to survivors who did not (HR 0.92; 95% CI 0.85-0.99). Survival benefit was also observed in survivors who underwent regular imaging up to 5 years from surgery (HR 0.68; 95% CI 0.60-0.78). CONCLUSIONS: More than half the lung cancer survivors received less than the recommended long-term surveillance imaging. Long-term adherence to surveillance is associated with improved survival. Our study provides evidence to support the current clinical guidelines for surveillance for lung cancer survivors that are primarily consensus-based at present.

Factors associated with high-risk human papillomavirus test utilization and infection: a population-based study of uninsured and underinsured women.

BACKGROUND: Current cervical cancer screening guidelines recommend a Pap test every 3 years for women age 21-65 years, or for women 30-65 years who want to lengthen the screening interval, a combination of Pap test and high-risk human papilloma virus testing (co-testing) every 5 years. Little population-based data are available on human papilloma virus test utilization and human papilloma virus infection rates. The objective of this study was to examine the patient-level, cervical cancer screening, and area-level factors associated with human papilloma virus testing and infection among a diverse sample of uninsured and underinsured women enrolled in the New Jersey Cancer Early Education and Detection (NJCEED) Program. METHODS: We used data for a sample of 50,510 uninsured/underinsured women, age ≥ 29 years, who screened for cervical cancer through NJCEED between January 1, 2009 and December 31, 2015. Multivariable logistic regression models were used to estimate associations between ever having a human papilloma virus test or a positive test result, and individual- (age, race/ethnicity, birthplace) and area-level covariates (% below federal poverty level, % minority, % uninsured), and number of screening visits. RESULTS: Only 26.6% (13,440) of the sample had at least one human papilloma virus test. Among women who underwent testing, 13.3% (1792) tested positive for human papilloma virus. Most women who were positive for human papilloma virus (99.4%) had their first test as a co-test. Human papilloma virus test utilization and infection were significantly associated with age, race/ethnicity, birthplace (country), and residential area-level poverty. Rates of human papilloma virus testing and infection also differed significantly across counties in the state of New Jersey. CONCLUSIONS: These findings suggest that despite access to no-cost cervical cancer screening for eligible women, human papilloma virus test utilization was relatively low among diverse, uninsured and underinsured women in New Jersey, and test utilization and infection were associated with individual-level and area-level factors.

PROMIS Peer Relationships Short Form: How Well Does Self-Report Correlate With Data From Peers?

Objective: To examine the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS®) peer relationships short form (PR-SF), including association with peer-reported friendships, likeability, and social reputation. Method: 203 children (Mage = 10.12 years, SD = 2.37, range = 6-14) in Grades 1-8 completed the 8-item PR-SF and friendship nominations, like ratings, and social reputation measures about their peers during 2 classroom visits approximately 4 months apart, as part of a larger study. A confirmatory factor analysis, followed by an exploratory factor analysis, was conducted to examine the factor structure of the PR-SF. Spearman correlations between the PR-SF and peer-reported outcomes evaluated construct validity. Results: For the PR-SF, a 2-factor solution demonstrated better fit than a 1-factor solution. The 2 factors appear to assess friendship quality (3 items) and peer acceptance (5 items). Reliability was marginal for the friendship quality factor (.66) but adequate for the acceptance factor (.85); stability was .34 for the PR-SF over 4 months. The PR-SF (8 items) and acceptance factor (5 items) both had modest but significant correlations with measures of friendship (rs = .25-.27), likeability (rs = .21-.22), and social reputation (rs = .29-.44). Conclusions: The PR-SF appears to be measuring two distinct aspects of social functioning. The 5-item peer acceptance scale is modestly associated with peer-reported friendship, likeability, and social reputation. Although not a replacement for peer-reported outcomes, the PR-SF is a promising patient-reported outcome for peer relationships in youth.

Down Syndrome Critical Region 1 Gene, Rcan1, Helps Maintain a More Fused Mitochondrial Network.

RATIONALE: The regulator of calcineurin 1 (RCAN1) inhibits CN (calcineurin), a Ca2+-activated protein phosphatase important in cardiac remodeling. In humans, RCAN1 is located on chromosome 21 in proximity to the Down syndrome critical region. The hearts and brains of Rcan1 KO mice are more susceptible to damage from ischemia/reperfusion (I/R); however, the underlying cause is not known. OBJECTIVE: Mitochondria are key mediators of I/R damage. The goal of these studies was to determine the impact of RCAN1 on mitochondrial dynamics and function. METHODS AND RESULTS: Using both neonatal and isolated adult cardiomyocytes, we show that, when RCAN1 is depleted, the mitochondrial network is more fragmented because of increased CN-dependent activation of the fission protein, DRP1 (dynamin-1-like). Mitochondria in RCAN1-depleted cardiomyocytes have reduced membrane potential, O2 consumption, and generation of reactive oxygen species, as well as a reduced capacity for mitochondrial Ca2+ uptake. RCAN1-depleted cardiomyocytes were more sensitive to I/R; however, pharmacological inhibition of CN, DRP1, or CAPN (calpains; Ca2+-activated proteases) restored protection, suggesting that in the absence of RCAN1, CAPN-mediated damage after I/R is greater because of a decrease in the capacity of mitochondria to buffer cytoplasmic Ca2+. Increasing RCAN1 levels by adenoviral infection was sufficient to enhance fusion and confer protection from I/R. To examine the impact of more modest, and biologically relevant, increases in RCAN1, we compared the mitochondrial network in induced pluripotent stem cells derived from individuals with Down syndrome to that of isogenic, disomic controls. Mitochondria were more fused, and O2 consumption was greater in the trisomic induced pluripotent stem cells; however, coupling efficiency and metabolic flexibility were compromised compared with disomic induced pluripotent stem cells. Depletion of RCAN1 from trisomic induced pluripotent stem cells was sufficient to normalize mitochondrial dynamics and function. CONCLUSIONS: RCAN1 helps maintain a more interconnected mitochondrial network, and maintaining appropriate RCAN1 levels is important to human health and disease.

Computed Tomography Colonography Less Costly Than Colonoscopy for Colorectal Cancer Screening of Commercially Insured Patients.

BACKGROUND: Computed tomography (CT) colonography's effectiveness, its associated patient advantages, and its potential role to increase colorectal cancer (CRC) screening rates have been demonstrated in previous research, but whether CT colonography has a cost advantage relative to optical colonoscopy for the commercially insured US population has not been assessed. OBJECTIVE: To compare the costs of CRC screening using CT colonography or optical colonoscopy for commercially insured people in the United States. METHODS: Using retrospective commercial healthcare claims data and peer-reviewed studies, we performed a simulated multiyear, matched-case comparison of the costs of CT and optical colonoscopies for CRC screening. We estimated commercial optical colonoscopy costs per screening based on the 2016 Truven Health MarketScan Commercial Database and ancillary services, such as bowel preparation, anesthesia, pathology, and complication costs. We developed 4 scenarios for CT colonography cost per screening using the ratio of commercial to Medicare fees, and calculated ancillary service and follow-up costs from payers' costs for these services when associated with optical colonoscopies. For comparison, we converted the costs per screening to the costs per screening year per person using real-world screening intervals that were obtained from peer-reviewed studies. RESULTS: In 2016, the average optical colonoscopy screening cost for commercial payers was $2033 (N = 406,068), or $340 per screening year per person. With our highest-cost CT colonography scenario, CT colonography costs 22% less, or $265 per screening year, than optical colonoscopy, mostly because of the advantages for patients of no anesthesia and the greatly reduced use of pathology services. CONCLUSIONS: The use of CT colonography for CRC testing offers effective screening, patient-centered advantages, and lower costs compared with optical colonoscopy, and may be particularly appealing to the currently unscreened population with commercial health insurance. If the availability of CT colonography expands to meet the increased demand for it, CT colonography could cost up to 50% less than optical colonoscopy per screening year.

Impact of Patient-Provider Race, Ethnicity, and Gender Concordance on Cancer Screening: Findings from Medical Expenditure Panel Survey.

Background: Racial and ethnic minorities experience lower rates of cancer screening compared with non-Hispanic whites (NHWs). Previous studies evaluating the role of patient-provider race, ethnicity, or gender concordance in cancer screening have been inconclusive.Methods: In a cross-sectional analysis using the Medical Expenditure Panel Survey (MEPS), data from 2003 to 2010 were assessed for associations between patient-provider race, ethnicity, and/or gender concordance and, screening (American Cancer Society guidelines) for breast, cervical, and colorectal cancer. Multivariable logistic analyses were conducted to examine associations of interest.Results: Of the 32,041 patient-provider pairs in our analysis, more than 60% of the patients were NHW, 15% were non-Hispanic black (NHB), and 15% were Hispanic. Overall, patients adherent to cancer screening were more likely to be non-Hispanic, better educated, married, wealthier, and privately insured. Patient-provider gender discordance was associated with lower rates of breast [OR, 0.83; 95% confidence interval (CI), 0.76-0.90], cervical (OR, 0.83; 95% CI, 0.76-0.91), and colorectal cancer (OR, 0.84; 95% CI, 0.79-0.90) screening in all patients. This association was also significant after adjusting for racial and/or ethnic concordance. Conversely, among NHWs and NHBs, patient-provider racial and/or ethnic concordance was not associated with screening. Among Hispanics, patient-provider ethnic discordant pairs had higher breast (58% vs. 52%) and colorectal cancer (45% vs. 39%) screening rates compared with concordant pairs.Conclusions: Patient-provider gender concordance positively affected cancer screening. Patient-provider ethnic concordance was inversely associated with receipt of cancer screening among Hispanics. This counter-intuitive finding requires further study.Impact: Our findings highlight the importance of gender concordance in improving cancer screening rates. Cancer Epidemiol Biomarkers Prev; 26(12); 1804-11. ©2017 AACR.

Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study.

Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive.Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. Cox proportional hazards models with time-varying covariates adjusted for propensity scores were used to assess the association while controlling for potential confounders.Results: Of 12,572 PDAC patients, 950 (7.56%) had used metformin alone, 4,506 (35.84%) had used statin alone, and 2,445 (19.45%) were dual users. Statin use was significantly associated with improved overall survival [HR, 0.94; 95% confidence interval (CI), 0.90-0.98], and survival was more pronounced in postdiagnosis statin users (HR, 0.69; 95% CI, 0.56-0.86). Metformin use was not significantly associated with overall survival (HR, 1.01; 95% CI, 0.94-1.09). No beneficial effect was observed for dual users (HR, 1.00; 95% CI, 0.95-1.05).Conclusions: Our findings suggest potential benefits of statins on improving survival among elderly PDAC patients; further prospective studies are warranted to corroborate the putative benefit of statin therapy in pancreatic cancer.Impact: Although more studies are needed to confirm our findings, our data add to the body of evidence on potential anticancer effects of statins. Cancer Epidemiol Biomarkers Prev; 26(8); 1225-32. ©2017 AACR.

Emotional processing during psychotherapy among women newly diagnosed with a gynecological cancer.

OBJECTIVE: Our aim was to compare changes in emotional processing by women newly diagnosed with gynecological cancer enrolled in either a coping and communication skills intervention (CCI) or a supportive counseling (SC) intervention. We examined the association between in-session emotional processing and patient-rated therapeutic progress. METHOD: Three therapy sessions with 201 patients were rated for the depth of emotional processing (peak and mode) during emotion episodes (EEs) using the Experiencing Rating Scale (EXP). Participants completed measures of dispositional emotional expressivity, depressive symptoms, and cancer-related distress before treatment began, as well as ratings of perceived progress in therapy after each session. RESULTS: Peak EXP ratings averaged between 2.7 and 3.1, indicating that women discussed events, their emotional reactions, and their private experiences in sessions. A small proportion of patients had high levels of processing, indicating deeper exploration of the meaning of their feelings and experiences. Women in SC were able to achieve a higher level of emotional processing during the middle and later sessions, and during cancer-related EEs in the later session. However, emotional processing was not significantly associated with a patient's perceived therapeutic progress with SC. In the CCI group, higher levels of emotional processing were associated with greater session progress, suggesting that it may play an important role in patient-rated treatment outcomes. SIGNIFICANCE OF RESULTS: Newly diagnosed gynecological cancer patients are able to attend to their emotions and personal experiences, particularly when discussing cancer-related issues during both short-term SC and prescriptive coping skills interventions.

Validation of a Contemporary Five-tiered Gleason Grade Grouping Using Population-based Data.

This population-based study assesses whether a proposed five-tiered Gleason grade grouping (GGG) system predicts prostate cancer-specific mortality (PCSM). Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 331320 prostate cancer patients who had primary and secondary Gleason patterns diagnosed between January 2006 and December 2012. We used the Fine and Gray proportional hazards model for subdistributions and the corresponding cumulative incidence to quantify the risk of PCSM. We found that the risk of PCSM approximately doubled with each GGG increase. Among men who underwent radical prostatectomy and using GGG1 (Gleason score ≤6) as the reference group, the adjusted hazard ratio for PCSM was 1.13 (95% confidence interval [CI] 0.83-1.54) for GGG2, 1.87 (95% CI 1.33-2.65) for GGG3, 5.03 (95% CI 3.59-7.06) for GGG4, and 10.92 (CI 8.03-14.84) for GGG5. Similar patterns were observed regardless of the type of primary cancer treatment received or clinical stage. In summary, our study, with large, racially diverse populations that reflect real world experiences, demonstrates that the new five-tiered GGG system predicts PCSM well regardless of treatment received or clinical stage at diagnosis. PATIENT SUMMARY: In this report we examined prostate cancer mortality using the new five-tiered cancer grading system using data for a large US population. We found that the new five-tiered cancer grading system can predict prostate cancer-specific mortality well, regardless of the type of primary cancer treatment and clinical stage. We conclude that this new five-tiered cancer grading system is useful in guiding treatment decisions.

Inhibition of class I histone deacetylases blunts cardiac hypertrophy through TSC2-dependent mTOR repression.

Altering chromatin structure through histone posttranslational modifications has emerged as a key driver of transcriptional responses in cells. Modulation of these transcriptional responses by pharmacological inhibition of class I histone deacetylases (HDACs), a group of chromatin remodeling enzymes, has been successful in blocking the growth of some cancer cell types. These inhibitors also attenuate the pathogenesis of pathological cardiac remodeling by blunting and even reversing pathological hypertrophy. The mechanistic target of rapamycin (mTOR) is a critical sensor and regulator of cell growth that, as part of mTOR complex 1 (mTORC1), drives changes in protein synthesis and metabolism in both pathological and physiological hypertrophy. We demonstrated through pharmacological and genetic methods that inhibition of class I HDACs suppressed pathological cardiac hypertrophy through inhibition of mTOR activity. Mice genetically silenced for HDAC1 and HDAC2 had a reduced hypertrophic response to thoracic aortic constriction (TAC) and showed reduced mTOR activity. We determined that the abundance of tuberous sclerosis complex 2 (TSC2), an mTOR inhibitor, was increased through a transcriptional mechanism in cardiomyocytes when class I HDACs were inhibited. In neonatal rat cardiomyocytes, loss of TSC2 abolished HDAC-dependent inhibition of mTOR activity, and increased expression of TSC2 was sufficient to reduce hypertrophy in response to phenylephrine. These findings point to mTOR and TSC2-dependent control of mTOR as critical components of the mechanism by which HDAC inhibitors blunt pathological cardiac growth. These results also suggest a strategy to modulate mTOR activity and facilitate the translational exploitation of HDAC inhibitors in heart disease.