Faculty Bibliography

High-dose melphalan followed by autologous stem cell transplantation remains the standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 h) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate that 2-h is at least as effective as 6-h cryotherapy in decreasing severe mucositis. From a population pharmacokinetic model, we identified that fat-free mass, hematocrit, and creatinine clearance were significant covariates, as reported previously. Furthermore, we observed the rs4240803 SLC7A5 polymorphism was significantly associated with pharmacokinetic variability, and pharmacokinetics was associated with both mucositis and neutropenia. However, melphalan exposure was not associated with progression-free or overall survival in our dataset. These findings contribute to ongoing efforts to personalize melphalan dosing in transplant patients.

Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40 mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively. Treatment was associated with reduction of serum CD44, a transmembrane glycoprotein associated with steroid and immunomodulatory drug resistance in MM. Our findings indicate that AR-42 is safe and that further investigation of AR-42 in combination regimens for the treatment of patients with lymphoma and MM is warranted.

OBJECTIVE:The Appalachian population suffers a disparate burden of chronic stress leading to high perceived stress. The study aim was to determine the association between perceived stress and Epstein-Barr virus (EBV) antibody titers, along with the impact of perceived social support, Appalachian self-identify, and health behaviors. METHODS:Serum EBV VCA-IgG antibody titer levels from 169 female Appalachian residents (aged 18-26 years) were examined. Perceived stress, perceived social support, Appalachian self-identity, and health behaviors were assessed via self-administered questionnaires. RESULTS:There were 169 of 185 women positive for EBV. Among these women, the median EBV antibody titer level was 404 U/mL (range 101-6,464), and the overall geometric mean was 563.2 (95% CI 486.6-651.9). For a 1-point increase in perceived stress, the EBV antibody titer increased by 1.92% (95% CI 0.04-3.76%). For every point increase in perceived social support, the EBV antibody titer decreased by 1.00% (95% CI 0.06-1.98%). Perceived stress was significantly associated with sleep quality, BMI, and current smoking status, but not with binge-drinking, drug use, or Appalachian self-identity. No mediating effects of sleep quality, BMI, binge-drinking, current drug use, or >4 sexual partners were observed in the relationship between perceived stress and EBV titer level. CONCLUSION/CONCLUSIONS:Young Appalachian women reported high levels of perceived stress that were significantly associated with higher EBV titers. Higher perceived social support was associated with lower EBV titers. Health behaviors and Appalachian self-identity did not impact the relationship between perceived stress and EBV titers.

Women from Appalachian regions of the United States (US) face a number of health related disparities, including mental health and substance misuse. Alcohol misuse is a significant public health concern among women in the US, associated with numerous adverse consequences for the woman, her unborn children, and any children in her care, yet data on correlates of risky alcohol use is limited among women from Appalachian Ohio. The current study examines the prevalence and predictors of risky alcohol use (e.g., heavy episodic drinking) in 2,349 women from 18 clinics in the Community Awareness Resources and Education I (CARE I) study in Appalachian Ohio. Alcohol use history was collected over the past 30 days. Regression models were employed to identify predictors of heavy episodic drinking. Results indicate that 20% of the current sample reported heavy episodic drinking. Being an emerging adult (18-26), single, a current smoker, and reporting a history of four or more partners were independently associated with heavy episodic drinking. Self-identifying as Appalachian was not protective or predictive of heavy episodic drinking. Further research identifying risk factors and enhancing protective factors will inform culturally competent preventive efforts, particularly for emerging adult women from Appalachian Ohio at risk for alcohol misuse and associated morbidities.

Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers.

This study evaluated the association between health related quality of life and food security among persons living with HIV (PLHIV). We studied 167 PLHIV who completed questionnaires assessing food security, disease symptomatology, and several domains of the SF-36 health related quality of life survey. HIV disease state was assessed from medical records. Associations between independent and outcome variables were determined through linear regression models. Compared to food security, very low food security was significantly associated with lower mental component summary scores, [average difference -4.98 (95 % CI -9.85, -0.10)]; mental health, [average difference -5.44 (95 % CI -10.08, -0.81)]; and general health, [average difference -5.13 (95 % CI -9.65, -0.65)] after adjusting for covariates. About a fourth of participants experienced severe food insecurity, which negatively influenced their mental health and general wellbeing. The inclusion of resources for food assistance in HIV treatment programs may help ameliorate mental health challenges faced by PLHIV.

BACKGROUND:Healthcare-associated infections (HAIs) impact patients' lives through prolonged hospitalization, morbidity, and death, resulting in significant costs to both health systems and society. Central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) are two of the most preventable HAIs. As a result, these HAIs have been the focus of significant efforts to identify evidence-based clinical strategies to reduce infection rates. The Comprehensive Unit-based Safety Program (CUSP) provides a formal model for translating CLABSI-reduction evidence into practice. Yet, a national demonstration project found organizations experienced variable levels of success using CUSP to reduce CLABSIs. In addition, in Fiscal year 2019, Medicare will expand use of CLABSI and CAUTI metrics beyond ICUs to the entire hospital for reimbursement purposes. As a result, hospitals need guidance about how to successfully translate HAI-reduction efforts such as CUSP to non-ICU settings (clinical practice), and how to shape context (management practice)-including culture and management strategies-to proactively support clinical teams. METHODS:Using a mixed-methods approach to evaluate the contribution of management factors to successful HAI-reduction efforts, our study aims to: (1) Develop valid and reliable measures of structural management practices associated with the recommended CLABSI Management Strategies for use as a survey (HAI Management Practice Guideline Survey) to support HAI-reduction efforts in both medical/surgical units and ICUs; (2) Develop, validate, and then deploy the HAI Management Practice Guideline Survey, first across Ohio hospitals, then nationwide, to determine the positive predictive value of the measurement instrument as it relates to CLABSI- and CAUTI-prevention; and (3) Integrate findings into a Management Practices Toolkit for HAI reduction that includes an organization-specific data dashboard for monitoring progress and an implementation program for toolkit use, and disseminate that Toolkit nationwide. DISCUSSION:Providing hospitals with the tools they need to successfully measure management structures that support clinical care provides a powerful approach that can be leveraged to reduce the incidence of HAIs experienced by patients. This study is critical to providing the information necessary to successfully "make health care safer" by providing guidance on how contextual factors within a healthcare setting can improve patient safety across hospitals.

PURPOSE/OBJECTIVE:To report our experience in long-term follow-up of ocular melanoma patients treated with custom OSU-Nag eye plaques using (125)I sources. METHODS:A retrospective chart review was conducted for 113 consecutive ocular melanoma patients with follow-up visual acuity data who were treated with OSU-Nag plaque episcleral brachytherapy at The Ohio State University Medical Center from 1994 to 2009. Visual acuity, complication data, and recurrence rates were recorded up to 120 months after brachytherapy. RESULTS:Median age at presentation was 63.0 years (range, 22-93). Median follow-up was 65.5 months (range, 2-180). Median radiation dose at the prescription point was 85.8 Gy (range, 51.8-103.7). Preservation of useful visual acuity, defined as better than 20/200, was noted in 43 of 74 (58%) of patients in the present study at 36 months compared with 50.1% of Collaborative Ocular Melanoma Study participants. By 120 months, 17 of 30 (57%; 95% confidence interval, 45-69%) progressed to visual acuity worse than 20/200, whereas 9 of 30 (30%) retained visual acuity of 20/40 or better, and 4 of 30 (13%) were 20/50-20/200. The rate of retinopathy after radiation was approximately 40% of all those observed by 60 months. Baseline visual acuity, apical tumor height, American Joint Committee on Cancer tumor category, and distance between the tumor and the fovea were all significantly associated with loss of visual acuity. The local tumor control rate by 60 months of follow-up was 93% (95% confidence interval, 85-97%). CONCLUSIONS:The OSU-Nag custom (125)I plaque is an effective treatment for uveal melanoma, with preservation of useful visual acuity in 58% of eyes 3 years after treatment and 43% of eyes 10 years after treatment.

BACKGROUND:The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a Ras-activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents. METHODS:This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic/recurrent KRAS-mutated or epidermal growth factor receptor (EGFR)-mutated/amplified non-small cell lung cancer. RESULTS:Thirty-seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF-V600E mutations. In total, 242 cycles (median, 4; range, 1-47) were completed. The initial doses were area under the curve (AUC) 6 mg/mL/min for carboplatin, 200 mg/m(2) for paclitaxel on day 1, and 3 × 10(10) 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21-day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175 mg/m(2) for paclitaxel and AUC 5 mg/mL/min for carboplatin. Toxicities included fatigue, diarrhea, nausea/vomiting, neutropenia, arthralgia/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1-sided lower confidence interval, 21%). Four SD patients had >40% positron emission tomography standardized uptake value reductions. The median progression-free survival, median overall survival, and 12-month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow-up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months. CONCLUSIONS:Reolysin in combination with paclitaxel and carboplatin was well tolerated. The observed response rate suggests a benefit of the reovirus for chemotherapy. A follow-up randomized study is recommended. The proportion of patients surviving longer than 2 years (30%) suggests a second/third-line treatment effect or possibly the triggering of an immune response after tumor reovirus infiltration.