Poornachand Veerapaneni

High priority for hepatitis C screening in safety net hospitals: Results from a prospective cohort of 4582 hospitalized baby boomers

Low‐income populations are disproportionately affected by hepatitis C virus (HCV) infection. Thus, implementing baby boomer screening (born 1945‐1965) for HCV may be a high priority for safety net hospitals. We report the prevalence and predictors of HCV infection and advanced fibrosis or cirrhosis based on the Fibrosis‐4 score plus imaging for a baby boomer cohort admitted to a safety net hospital over a 21‐month interval with >9 months of follow‐up. Anti‐HCV antibody testing was performed for 4582, or 90%, of all never‐screened patients, of whom 312 (6.7%) tested positive. Adjusted odds ratios of testing anti‐HCV‐positive were 2.66 for men versus women (P < 0.001), 1.25 for uninsured versus insured (P = 0.06), 0.70 for Hispanics versus non‐Hispanic whites (P = 0.005), and 0.93 per year of age (P < 0.001). Among 287 patients tested for HCV RNA (91% of all anti‐HCV‐positive cases), 175 (61%) were viremic (3.8% overall prevalence in cohort), which was 5% less likely per year of age (P < 0.03). Noninvasive staging of 148 (84.6%) chronic HCV patients identified advanced fibrosis or cirrhosis in 50 (33.8%), with higher adjusted odds ratios of 3.21 for Hispanics versus non‐Hispanic whites/Asians (P = 0.02) and 1.18 per year of age (P = 0.001). Other factors associated with significantly higher adjusted odds ratios of advanced fibrosis or cirrhosis were alcohol abuse/dependence, obesity, and being uninsured. Conclusion: In this low‐income, hospitalized cohort, 4% of 4582 screened baby boomers were diagnosed with chronic HCV, nearly twice the rate in the community; one‐third had noninvasive testing that indicated advanced fibrosis or cirrhosis, which was significantly more likely for Hispanics, those of older age, those with obesity, those with alcohol abuse/dependence, and those who lacked insurance. (Hepatology 2015;62:1388–1395)

Implementing hospital-based baby boomer hepatitis c virus screening and linkage to care: Strategies, results, and costs

BACKGROUND/OBJECTIVE The US Preventive Services Task Force recommends 1-time hepatitis C virus (HCV) screening of all baby boomers (born 1945-1965). However, little is known about optimal ways to implement HCV screening, counseling, and linkage to care. We developed strategies following approaches used for HIV to implement baby boomer HCV screening in a hospital setting and report results as well as costs. DESIGN/PATIENTS Prospective cohort of 6140 baby boomers admitted to a safety-net hospital in South Texas from December 1, 2012 to January 31, 2014 and followed to December 10, 2014. PROCEDURES/MEASUREMENTS The HCV screening program included clinician/staff education, electronic medical record algorithm for eligibility and order entry, opt-out consent, anti-HCV antibody test with reflex HCV RNA, personalized inpatient counseling, and outpatient case management. Outcomes were anti-HCV antibody-positive and HCV RNA-positive results. RESULTS Of 3168 eligible patients, 240 (7.6%) were anti-HCV positive, which was more likely (P < 0.05) for younger age, men, and uninsured. Of 214 (89.2%) patients tested for HCV RNA, 134 (4.2% of all screened) were positive (chronic HCV). Among patients with chronic HCV, 129 (96.3%) were counseled, 108 (80.6%) received follow-up primary care, and 52 (38.8%) received hepatology care. Five patients initiated anti-HCV therapy. Total costs for start-up and implementation for 14 months were

High priority for hepatitis C screening in safety net hospitals

286,482. CONCLUSIONS This inpatient HCV screening program diagnosed chronic HCV infection in 4.2% of tested patients and linked >80% to follow-up care. Yet access to therapy is challenging for largely uninsured populations, and most programmatic costs of the program are not currently covered.

Relationship Quality and Patient-Assessed Quality of Care in VA Primary Care Clinics: Development and Validation of the Work Relationships Scale

Low‐income populations are disproportionately affected by hepatitis C virus (HCV) infection. Thus, implementing baby boomer screening (born 1945‐1965) for HCV may be a high priority for safety net hospitals. We report the prevalence and predictors of HCV infection and advanced fibrosis or cirrhosis based on the Fibrosis‐4 score plus imaging for a baby boomer cohort admitted to a safety net hospital over a 21‐month interval with >9 months of follow‐up. Anti‐HCV antibody testing was performed for 4582, or 90%, of all never‐screened patients, of whom 312 (6.7%) tested positive. Adjusted odds ratios of testing anti‐HCV‐positive were 2.66 for men versus women (P < 0.001), 1.25 for uninsured versus insured (P = 0.06), 0.70 for Hispanics versus non‐Hispanic whites (P = 0.005), and 0.93 per year of age (P < 0.001). Among 287 patients tested for HCV RNA (91% of all anti‐HCV‐positive cases), 175 (61%) were viremic (3.8% overall prevalence in cohort), which was 5% less likely per year of age (P < 0.03). Noninvasive staging of 148 (84.6%) chronic HCV patients identified advanced fibrosis or cirrhosis in 50 (33.8%), with higher adjusted odds ratios of 3.21 for Hispanics versus non‐Hispanic whites/Asians (P = 0.02) and 1.18 per year of age (P = 0.001). Other factors associated with significantly higher adjusted odds ratios of advanced fibrosis or cirrhosis were alcohol abuse/dependence, obesity, and being uninsured. Conclusion: In this low‐income, hospitalized cohort, 4% of 4582 screened baby boomers were diagnosed with chronic HCV, nearly twice the rate in the community; one‐third had noninvasive testing that indicated advanced fibrosis or cirrhosis, which was significantly more likely for Hispanics, those of older age, those with obesity, those with alcohol abuse/dependence, and those who lacked insurance. (Hepatology 2015;62:1388–1395)

Elevated aromatase expression correlates with cervical carcinoma progression

PURPOSE Efforts to better understand the impact of clinic member relationships on care quality in primary care clinics have been limited by the absence of a validated instrument to assess these relationships. The purpose of this study was to develop and validate a scale assessing relationships within primary care clinics. METHODS The Work Relationships Scale (WRS) was developed and administered as part of a survey of learning and relationships among 17 Department of Veterans Affairs (VA) primary care clinics. A Rasch partial-credit model and principal components analysis were used to evaluate item performance, select the final items for inclusion, and establish unidimensionality for the WRS. The WRS was then validated against semistructured clinic member interviews and VA Survey of Healthcare Experiences of Patients (SHEP) data. RESULTS Four hundred fifty-seven clinicians and staff completed the clinic survey, and 247 participated in semistructured interviews. WRS scores were significantly associated with clinic-level reporting for 2 SHEP variables: overall rating of personal doctor/nurse (r2 =0.43, P <.01) and overall rating of health care (r2= 0.25, P <.05). Interview data describing relationship characteristics were consistent with variability in WRS scores across low-scoring and high-scoring clinics. CONCLUSIONS The WRS shows promising validity as a measure assessing the quality of relationships in primary care settings; moreover, primary care clinics with lower WRS scores received poorer patient quality ratings for both individual clinicians and overall health care. Relationships play an important role in shaping care delivery and should be assessed as part of efforts to improve patient care within primary care settings.

A patient-centered surgical home to improve outpatient surgical processes of care and outcomes

OBJECTIVES We have previously demonstrated that aromatase mRNA is induced in cervical carcinomas compared to normal tissue, suggesting that in situ aromatase expression leading to elevated local estrogen production may contribute to cervical carcinogensis. Our objectives are to examine 1) whether aromatase protein and activity are induced in cervical carcinomas, 2) aromatase expression correlates with disease stage, and 3) inflammatory cytokines (e.g., IL-6 and TNFalpha) may correlate with aromatase expression. METHODS RNA and protein were isolated from human cervical carcinomas and normal cervical biopsies to examine aromatase expression, using real-time RT-PCR, Western blot analysis, and immunohistochemistry. Aromatase activity in tissue was measured using the tritiated water release method. IL-6 and TNFalpha expression was also examined. RESULTS Aromatase protein and activity levels were increased in cervical carcinomas compared to normal tissue. RNA levels correlated significantly with disease progression, with highest aromatase expression detected in stage IV tumors (p<0.001, R(2)=0.77). Aromatase promoters 1.3 and 1.4 were elevated in cervical carcinomas and in cervical cancer cells. The expression of inflammatory cytokines IL-6 and TNFalpha, known to induce aromatase, significantly correlated with aromatase expression (R(2)>0.9). TNFalpha treatment induced aromatase expression in cervical cancer cells. CONCLUSION Increased aromatase protein and activity in cervical carcinomas and the correlation of its expression with disease stage implicates it in cervical carcinogenesis. The correlation of IL-6 and TNFalpha expression with aromatase suggests that these inflammatory cytokines may induce aromatase expression, which is confirmed by induction of aromatase expression due to TNFalpha treatment of cervical cancer cells.

Hospital-Based Hepatitis C Screening of Baby Boomers in a Majority Hispanic South Texas Cohort: Successes and Barriers to Implementation

Preparing patients for surgery is critical for achieving the best possible surgical outcomes. To do this effectively, care must be coordinated across several types of specialists, and potentially across multiple settings. In this paper, we develop a Patient-Centered Surgical Home (PCSH) for outpatient surgery based on the concept of the Perioperative Surgical Home proposed by the American Society of Anesthesiologists. A key feature of the PCSH is to have an anesthesiology preoperative assessment clinic (APC) serve as system coordinator and information integrator. Based on a study of outpatient surgery at the University of Texas Health Science Center at San Antonio and its primary teaching hospital using statistical analysis and simulation, we demonstrate how this can be accomplished. We show that for the PCSH to succeed, APC must see the right patients with the right information by overcoming improper triaging of patients and patient information deficiencies. Our analysis shows that with the proper screening tool and modifications to the way triage is handled, it is possible to increase the number of patients that the APC sees each day with a modest increase in resources. Much of the potential benefits rest on the cooperation of the referring clinics as well as closing the gap between the current level of patient information and what is needed for optimizing medical decisions. Estimated cost savings are over one million dollars annually with a PCSH. Since APC-like clinics are common, our findings have great potential for widespread implementation of similar PCSH models with commensurate benefits.

A simulation analysis of a patient-centered surgical home to improve outpatient surgical processes of care and outcomes

Objective. To comply with the 2012 CDC recommendations for hepatitis C virus (HCV) screening, we implemented a new HCV screening program for patients born between 1945 and 1965 at a South Texas safety-net hospital. Methods. Patients with no HCV diagnosis or prior HCV test received an automated order for HCV antibody (anti-HCV) tests combined with reflex HCV ribonucleic acid (RNA) polymerase chain reaction. An inpatient counselor educated anti-HCV-positive patients. A bilingual patient navigator assisted newly diagnosed chronic HCV patients with linkage to primary and specialty care. We examined results for Hispanic vs. non-Hispanic patients in the first 10 months of project implementation in 2013–2014. Results. Of 2,327 patients screened for HCV, the 192 (8%) patients who tested anti-HCV positive were younger than those who tested negative (56 vs. 58 years, respectively, p<0.001) and more likely to be male (p<0.001). Of the 167 anti-HCV-positive patients tested for HCV RNA, 108 (65%) were HCV RNA positive (5% of cohort). Barriers to care for HCV RNA-positive patients included a lack of health insurance, current substance abuse, incarceration, and homelessness. Hispanic HCV RNA-positive patients were more likely than non-Hispanic HCV RNA-positive patients to be substance abusers or incarcerated. Of all HCV RNA-positive patients, 103 patients (95%) received counseling, 94 patients (87%) were linked to primary care, 47 patients (44%) were linked to specialty care, and eight patients (7%) started treatment. Conclusion. The prevalence of anti-HCV-positive and chronically HCV-infected patients was higher than many Hispanic or non-Hispanic white cohorts. Most Hispanic patients newly diagnosed with chronic HCV had barriers to care for HCV infection that must be overcome if HCV screening is to reduce morbidity and mortality in this population.

Preclinical modeling of endocrine response: a combination therapy approach with the ERβ agonist, diarryl propionitrile and letrozole restores sensitivity to letrozole-resistant breast cancer cells.

The process of preparing patients for outpatient surgery is information intensive. However, medical records are often fragmented among different providers and systems. As a result, the preoperative assessment process is frequently prolonged by missing information, potentially leading to surgery delay or cancellation. In this study, we simulate an anesthesiology pre-operative assessment clinic to quantify the impact of patient information deficiency and to assist in the development of a patient-centered surgical home to mitigate this problem through better system-wide coordination.

Abstract 319: Isoform-specific induction of MAPK p38 in cervical cancer

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #17 The majority of breast cancer patients are postmenopausal women with estrogen receptor-positive (ER+) tumors. Approximately 66% of breast carcinomas contain aromatase. Aromatase inhibitors are proving to be more effective than tamoxifen in the treatment of postmenopausal women with ER+ breast cancer. However, the development of resistance to treatment is a concern. The transition of the ER+ tumors from a responsive to unresponsive state is associated with different molecular pathways. We have therefore investigated the properties of resistance that develops in response to the aromatase inhibitor letrozole in the preclinical MCF-7-aromatase xenograft animal model following long-term treatment with letrozole by using the derived letrozole-resistant MCF-7-aromatase LTLTca breast cancer cells. The combination treatment of letrozole and the ERβ agonist diarryl propionitrile (DPN) restored sensitivity to letrozole in the letrozole-resistant LTLTca cells. Studies from our group using this postmenopausal breast cancer preclinical model clearly showed the therapeutic advantage of the ERβ agonist in overcoming unresponsiveness to letrozole. A 67% reduction in tumour size was observed in the group of animals bearing the letrozole-resistant LTLTca tumors that received the combination of letrozole and DPN. A novel delivery method using letrozole-DPN nanoparticles showed enhanced sensitivity (∼80%) to the combination nanoparticles. Letrozole was found to be relatively ineffective in these animals with only a 36% reduction in tumor size with tumors having a mean tumor weight of 0.95g by the end of four weeks of treatment. Biochemical analysis showed a reduction in the tumor aromatase enzyme levels in mice treated with letrozole + DPN when compared to letrozole alone. QRT-PCR as well as protein analysis studies of the letrozole-resistant LTLTca tumors showed a decrease in P27 levels and elevated expression levels of HER-2. Expression levels of cyclin D1 and the ERα to ERb ratio was higher in the untreated letrozole-resistant tumors compared to tumors that responded to the combination therapy. These findings provide further support for the development and testing of novel therapeutic approaches for selective regulation of ER-dependent (ERα and β) actions. Combination treatments involving agents that modulate ERβ activity may provide therapeutic advantage in the treatment, for overcoming resistance to estrogen-ablation and prevention of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 17.